Dr Nikhil Dhurandhar John H Hernandez Professor in Health Promotion Louisiana State University

INFECTOBESITY Obesity of Infectious Origin

Nikhil V Dhurandhar

John H Hernandez Endowed Professor in Health Promotion

Infection and Obesity Laboratory

Pennington Biomedical Research Center

Louisiana State University System

Baton Rouge Louisiana

Salzburg Austria 2012

ldquoMost Obese persons will not stay in treatment for Obesity

Of those who stay in treatment most will not lose weight

and of those who do lose weight most will regain itrdquo

- Albert Stunkard 1958

EAT LESS MOVE MORE

TREATMENT VS RESEARCH

eg CANCER HIV

Just one big meal does not cause obesity

Just one small meal does not fix obesity

The search for

effective amp meaningful approaches

OBESITY

A complex disease with multi-factorial etiology

It requires a multi-factorial treatment and

prevention approach

CAUSE-SPECIFIC APPROACH

Different prevention amp treatment strategies

BETTER RESULTS

Infections Endocrine disrupters Sleep debt

Pharmaceutical iatrogenesis Ambient temperature

Intrauterine and Intergenerational effects Epigenetics

Maternal age Assortative mating

Is Obesity an infectious disease

Is Gastric Ulcer an infectious disease

Causes of gastric ulcer

Hurry

Worry

and Curry

Photo httpenwikipediaorgwikiFileRobin_Warrenjpg

THE NOBEL PRIZE IN PHYSIOLOGY OR MEDICINE

Barry J Marshall J Robin Warren

ldquofor their discovery of the

Bacterium

Helicobacter pylori

and its role in

Gastritis and peptic

ulcer diseaserdquo

2005

INFECTOBESITY Obesity of Infectious Origin

Nikhil V Dhurandhar

John H Hernandez Endowed Professor in Health Promotion

Infection and Obesity Laboratory

Pennington Biomedical Research Center

Louisiana State University System

Baton Rouge Louisiana

Salzburg Austria 2012

ldquoMost Obese persons will not stay in treatment for Obesity

Of those who stay in treatment most will not lose weight

and of those who do lose weight most will regain itrdquo

- Albert Stunkard 1958

EAT LESS MOVE MORE

TREATMENT VS RESEARCH

eg CANCER HIV

Just one big meal does not cause obesity

Just one small meal does not fix obesity

The search for

effective amp meaningful approaches

OBESITY

A complex disease with multi-factorial etiology

It requires a multi-factorial treatment and

prevention approach

CAUSE-SPECIFIC APPROACH

Different prevention amp treatment strategies

BETTER RESULTS

Infections Endocrine disrupters Sleep debt

Pharmaceutical iatrogenesis Ambient temperature

Intrauterine and Intergenerational effects Epigenetics

Maternal age Assortative mating

Is Obesity an infectious disease

Is Gastric Ulcer an infectious disease

Causes of gastric ulcer

Hurry

Worry

and Curry

Photo httpenwikipediaorgwikiFileRobin_Warrenjpg

THE NOBEL PRIZE IN PHYSIOLOGY OR MEDICINE

Barry J Marshall J Robin Warren

ldquofor their discovery of the

Bacterium

Helicobacter pylori

and its role in

Gastritis and peptic

ulcer diseaserdquo

2005

ldquoMost Obese persons will not stay in treatment for Obesity

Of those who stay in treatment most will not lose weight

and of those who do lose weight most will regain itrdquo

- Albert Stunkard 1958

EAT LESS MOVE MORE

TREATMENT VS RESEARCH

eg CANCER HIV

Just one big meal does not cause obesity

Just one small meal does not fix obesity

The search for

effective amp meaningful approaches

OBESITY

A complex disease with multi-factorial etiology

It requires a multi-factorial treatment and

prevention approach

CAUSE-SPECIFIC APPROACH

Different prevention amp treatment strategies

BETTER RESULTS

Infections Endocrine disrupters Sleep debt

Pharmaceutical iatrogenesis Ambient temperature

Intrauterine and Intergenerational effects Epigenetics

Maternal age Assortative mating

Is Obesity an infectious disease

Is Gastric Ulcer an infectious disease

Causes of gastric ulcer

Hurry

Worry

and Curry

Photo httpenwikipediaorgwikiFileRobin_Warrenjpg

THE NOBEL PRIZE IN PHYSIOLOGY OR MEDICINE

Barry J Marshall J Robin Warren

ldquofor their discovery of the

Bacterium

Helicobacter pylori

and its role in

Gastritis and peptic

ulcer diseaserdquo

2005

EAT LESS MOVE MORE

TREATMENT VS RESEARCH

eg CANCER HIV

Just one big meal does not cause obesity

Just one small meal does not fix obesity

The search for

effective amp meaningful approaches

OBESITY

A complex disease with multi-factorial etiology

It requires a multi-factorial treatment and

prevention approach

CAUSE-SPECIFIC APPROACH

Different prevention amp treatment strategies

BETTER RESULTS

Infections Endocrine disrupters Sleep debt

Pharmaceutical iatrogenesis Ambient temperature

Intrauterine and Intergenerational effects Epigenetics

Maternal age Assortative mating

Is Obesity an infectious disease

Is Gastric Ulcer an infectious disease

Causes of gastric ulcer

Hurry

Worry

and Curry

Photo httpenwikipediaorgwikiFileRobin_Warrenjpg

THE NOBEL PRIZE IN PHYSIOLOGY OR MEDICINE

Barry J Marshall J Robin Warren

ldquofor their discovery of the

Bacterium

Helicobacter pylori

and its role in

Gastritis and peptic

ulcer diseaserdquo

2005

TREATMENT VS RESEARCH

eg CANCER HIV

Just one big meal does not cause obesity

Just one small meal does not fix obesity

The search for

effective amp meaningful approaches

OBESITY

A complex disease with multi-factorial etiology

It requires a multi-factorial treatment and

prevention approach

CAUSE-SPECIFIC APPROACH

Different prevention amp treatment strategies

BETTER RESULTS

Infections Endocrine disrupters Sleep debt

Pharmaceutical iatrogenesis Ambient temperature

Intrauterine and Intergenerational effects Epigenetics

Maternal age Assortative mating

Is Obesity an infectious disease

Is Gastric Ulcer an infectious disease

Causes of gastric ulcer

Hurry

Worry

and Curry

Photo httpenwikipediaorgwikiFileRobin_Warrenjpg

THE NOBEL PRIZE IN PHYSIOLOGY OR MEDICINE

Barry J Marshall J Robin Warren

ldquofor their discovery of the

Bacterium

Helicobacter pylori

and its role in

Gastritis and peptic

ulcer diseaserdquo

2005

Just one big meal does not cause obesity

Just one small meal does not fix obesity

The search for

effective amp meaningful approaches

OBESITY

A complex disease with multi-factorial etiology

It requires a multi-factorial treatment and

prevention approach

CAUSE-SPECIFIC APPROACH

Different prevention amp treatment strategies

BETTER RESULTS

Infections Endocrine disrupters Sleep debt

Pharmaceutical iatrogenesis Ambient temperature

Intrauterine and Intergenerational effects Epigenetics

Maternal age Assortative mating

Is Obesity an infectious disease

Is Gastric Ulcer an infectious disease

Causes of gastric ulcer

Hurry

Worry

and Curry

Photo httpenwikipediaorgwikiFileRobin_Warrenjpg

THE NOBEL PRIZE IN PHYSIOLOGY OR MEDICINE

Barry J Marshall J Robin Warren

ldquofor their discovery of the

Bacterium

Helicobacter pylori

and its role in

Gastritis and peptic

ulcer diseaserdquo

2005

The search for

effective amp meaningful approaches

OBESITY

A complex disease with multi-factorial etiology

It requires a multi-factorial treatment and

prevention approach

CAUSE-SPECIFIC APPROACH

Different prevention amp treatment strategies

BETTER RESULTS

Infections Endocrine disrupters Sleep debt

Pharmaceutical iatrogenesis Ambient temperature

Intrauterine and Intergenerational effects Epigenetics

Maternal age Assortative mating

Is Obesity an infectious disease

Is Gastric Ulcer an infectious disease

Causes of gastric ulcer

Hurry

Worry

and Curry

Photo httpenwikipediaorgwikiFileRobin_Warrenjpg

THE NOBEL PRIZE IN PHYSIOLOGY OR MEDICINE

Barry J Marshall J Robin Warren

ldquofor their discovery of the

Bacterium

Helicobacter pylori

and its role in

Gastritis and peptic

ulcer diseaserdquo

2005

OBESITY

A complex disease with multi-factorial etiology

It requires a multi-factorial treatment and

prevention approach

CAUSE-SPECIFIC APPROACH

Different prevention amp treatment strategies

BETTER RESULTS

Infections Endocrine disrupters Sleep debt

Pharmaceutical iatrogenesis Ambient temperature

Intrauterine and Intergenerational effects Epigenetics

Maternal age Assortative mating

Is Obesity an infectious disease

Is Gastric Ulcer an infectious disease

Causes of gastric ulcer

Hurry

Worry

and Curry

Photo httpenwikipediaorgwikiFileRobin_Warrenjpg

THE NOBEL PRIZE IN PHYSIOLOGY OR MEDICINE

Barry J Marshall J Robin Warren

ldquofor their discovery of the

Bacterium

Helicobacter pylori

and its role in

Gastritis and peptic

ulcer diseaserdquo

2005

CAUSE-SPECIFIC APPROACH

Different prevention amp treatment strategies

BETTER RESULTS

Infections Endocrine disrupters Sleep debt

Pharmaceutical iatrogenesis Ambient temperature

Intrauterine and Intergenerational effects Epigenetics

Maternal age Assortative mating

Is Obesity an infectious disease

Is Gastric Ulcer an infectious disease

Causes of gastric ulcer

Hurry

Worry

and Curry

Photo httpenwikipediaorgwikiFileRobin_Warrenjpg

THE NOBEL PRIZE IN PHYSIOLOGY OR MEDICINE

Barry J Marshall J Robin Warren

ldquofor their discovery of the

Bacterium

Helicobacter pylori

and its role in

Gastritis and peptic

ulcer diseaserdquo

2005

Infections Endocrine disrupters Sleep debt

Pharmaceutical iatrogenesis Ambient temperature

Intrauterine and Intergenerational effects Epigenetics

Maternal age Assortative mating

Is Obesity an infectious disease

Is Gastric Ulcer an infectious disease

Causes of gastric ulcer

Hurry

Worry

and Curry

Photo httpenwikipediaorgwikiFileRobin_Warrenjpg

THE NOBEL PRIZE IN PHYSIOLOGY OR MEDICINE

Barry J Marshall J Robin Warren

ldquofor their discovery of the

Bacterium

Helicobacter pylori

and its role in

Gastritis and peptic

ulcer diseaserdquo

2005

Is Obesity an infectious disease

Is Gastric Ulcer an infectious disease

Causes of gastric ulcer

Hurry

Worry

and Curry

Photo httpenwikipediaorgwikiFileRobin_Warrenjpg

THE NOBEL PRIZE IN PHYSIOLOGY OR MEDICINE

Barry J Marshall J Robin Warren

ldquofor their discovery of the

Bacterium

Helicobacter pylori

and its role in

Gastritis and peptic

ulcer diseaserdquo

2005

Is Gastric Ulcer an infectious disease

Causes of gastric ulcer

Hurry

Worry

and Curry

Photo httpenwikipediaorgwikiFileRobin_Warrenjpg

THE NOBEL PRIZE IN PHYSIOLOGY OR MEDICINE

Barry J Marshall J Robin Warren

ldquofor their discovery of the

Bacterium

Helicobacter pylori

and its role in

Gastritis and peptic

ulcer diseaserdquo

2005

Causes of gastric ulcer

Hurry

Worry

and Curry

Photo httpenwikipediaorgwikiFileRobin_Warrenjpg

THE NOBEL PRIZE IN PHYSIOLOGY OR MEDICINE

Barry J Marshall J Robin Warren

ldquofor their discovery of the

Bacterium

Helicobacter pylori

and its role in

Gastritis and peptic

ulcer diseaserdquo

2005

Photo httpenwikipediaorgwikiFileRobin_Warrenjpg

THE NOBEL PRIZE IN PHYSIOLOGY OR MEDICINE

Barry J Marshall J Robin Warren

ldquofor their discovery of the

Bacterium

Helicobacter pylori

and its role in

Gastritis and peptic

ulcer diseaserdquo

2005

Obesity of infectious origin

INFECTOBESITY

Significance of Infectobesity Research

1) Obesity has multifactorial etiology but the treatment

is not cause-specific

2) Specific prevention treatment strategies

3) Small pox eradication

INFECTOBESITY

httpwwwflickrcomcamerassonydsc-w55

UNIVERSITY OF MUMBAI

Dhurandhar NV et al Vet Microbiol 1992 31 101-107

Dhurandhar NV et al Obesity Res 1997 5464-69

Dhurandhar NV et al J Bom Vet College 1990 2131-32

Chickens SMAM-1 increases adiposity amp reduced serum lipids

Obese Humans SMAM-1 is associated with greater BMI and lower lipids

AVIAN ADENOVIRUS SMAM-1 INCREASES BODY FAT

Adipogenic microbes 1 Canine Distemper Virus Lyons et al 1982

2 RAV-7 Carter et al 1983 3 Borna Disease Virus Gosztonyi et al 1985 4 Scrapie agents Kim et al 1987 5 Avian adenovirus SMAM-1 Dhurandhar et al 1992 6 Human adenovirus Ad36 Dhurandhar et al 1999

7 Human adenovirus Ad37 Atkinson et al 2005 8 Human adenovirus Ad5 So et al 2005 9 Gut microbiota in mice Backhed et al 2004 10 Protozoal parasites in Dragon Fly Schlider et al 2006 11 Chlamydia pneumoniae Dart et al 2002 12 Oral bacteria ndash selenomonas noxia Goodson et al 2009

0

20

40

60

80

100

o

be

se

Obesity Prevelance

Control

Ad36

Dhurandhar et al Int J Obes 200125990-996

Dhurandhar et al J Nutr 2002 1323155-3160

Dhurandhar et al Int J Obes 200024989-996

Pasarica et al Obesity 2006 14 (11) 1905-13

AD-36 INCREASES ADIPOSITY IN ANIMAL MODELS

0

5

10

15

20

25

30

35

40

45

0 2 4 6 8 10 12 14 16 18 20 22 24 26

Weeks post inoculation

We

igh

t c

ha

ng

e (

g)

Ad-36

Control

0

4

8

12

16

Total Body Fat ()

Ad-36

Control

Weight change Body fat

AD-36 INCREASES ADIPOSITY IN MARMOSETS

Virus-induced obesity

Mechanism of Action

STEM CELLS

ADIPOCYTE

PRE-

ADIPOCYTE

Mechanism of action of Ad36

Adipose tissue expansion by increasing proliferation

commitment differentiation and lipid accumulation in

adipocyte progenitors ASC

Virus-induced obesity

A causative role in humans

Challenges

1 Obesity has insidious onset

2 Multiple etiological factors ndash difficult to attribute to a factor

3 A combination of infection with other factors needed

4 Ethical reasons preclude experimental infection of humans

Do certain infections cause human obesity

Twin Study

Body weight of twins is similar

Hypothesis

Ad36 infected co-twins will be heavier compared

to uninfected co-twins

Twin pairs (n=26) discordant for Ad-36 antibodies

Antibody + Antibody -

Age (y) 330 plusmn 157 330 plusmn 157

Sex ( F M) 77 23 77 23

BMI (kgm2) 245 plusmn 52 231 plusmn 45

Body fat () 296 plusmn 95 275 plusmn 99

Int J Obesity 2005 29(3)281-6

Exposure to Ad36 was associated with

a) greater fat at baseline

b) greater increase in fat

Lin WY et al Diabetes Care Nov 2012

Serum samples of 1400 Mexican American individuals

Longitudinal study ndash 10 y follow up

Dhurandhar NV Lancet Inf Dis 2011 11963-69

USA

CA GA MD

MO (WI MI LA VA)

Canada Mexico

Korea China

Sweden Belgium

The Czech Republic

Italy Poland

Turkey

Australia

AD-36 STUDIES

Ad36 amp BMI

Ad36 amp Obesity

EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN

HUMANS

Obesity 2013 Jun 26 doi 101002oby20533

Serological data analyses show that adenovirus

36 infection is associated with obesity

A meta-analysis involving 5739 subjects

Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H

Significance of Infectobesity Research

1) Obesity has multifactorial etiology but the treatment

is not cause-specific

2) Specific prevention treatment strategies

3) Small pox eradication

INFECTOBESITY

httpwwwflickrcomcamerassonydsc-w55

UNIVERSITY OF MUMBAI

Dhurandhar NV et al Vet Microbiol 1992 31 101-107

Dhurandhar NV et al Obesity Res 1997 5464-69

Dhurandhar NV et al J Bom Vet College 1990 2131-32

Chickens SMAM-1 increases adiposity amp reduced serum lipids

Obese Humans SMAM-1 is associated with greater BMI and lower lipids

AVIAN ADENOVIRUS SMAM-1 INCREASES BODY FAT

Adipogenic microbes 1 Canine Distemper Virus Lyons et al 1982

2 RAV-7 Carter et al 1983 3 Borna Disease Virus Gosztonyi et al 1985 4 Scrapie agents Kim et al 1987 5 Avian adenovirus SMAM-1 Dhurandhar et al 1992 6 Human adenovirus Ad36 Dhurandhar et al 1999

7 Human adenovirus Ad37 Atkinson et al 2005 8 Human adenovirus Ad5 So et al 2005 9 Gut microbiota in mice Backhed et al 2004 10 Protozoal parasites in Dragon Fly Schlider et al 2006 11 Chlamydia pneumoniae Dart et al 2002 12 Oral bacteria ndash selenomonas noxia Goodson et al 2009

0

20

40

60

80

100

o

be

se

Obesity Prevelance

Control

Ad36

Dhurandhar et al Int J Obes 200125990-996

Dhurandhar et al J Nutr 2002 1323155-3160

Dhurandhar et al Int J Obes 200024989-996

Pasarica et al Obesity 2006 14 (11) 1905-13

AD-36 INCREASES ADIPOSITY IN ANIMAL MODELS

0

5

10

15

20

25

30

35

40

45

0 2 4 6 8 10 12 14 16 18 20 22 24 26

Weeks post inoculation

We

igh

t c

ha

ng

e (

g)

Ad-36

Control

0

4

8

12

16

Total Body Fat ()

Ad-36

Control

Weight change Body fat

AD-36 INCREASES ADIPOSITY IN MARMOSETS

Virus-induced obesity

Mechanism of Action

STEM CELLS

ADIPOCYTE

PRE-

ADIPOCYTE

Mechanism of action of Ad36

Adipose tissue expansion by increasing proliferation

commitment differentiation and lipid accumulation in

adipocyte progenitors ASC

Virus-induced obesity

A causative role in humans

Challenges

1 Obesity has insidious onset

2 Multiple etiological factors ndash difficult to attribute to a factor

3 A combination of infection with other factors needed

4 Ethical reasons preclude experimental infection of humans

Do certain infections cause human obesity

Twin Study

Body weight of twins is similar

Hypothesis

Ad36 infected co-twins will be heavier compared

to uninfected co-twins

Twin pairs (n=26) discordant for Ad-36 antibodies

Antibody + Antibody -

Age (y) 330 plusmn 157 330 plusmn 157

Sex ( F M) 77 23 77 23

BMI (kgm2) 245 plusmn 52 231 plusmn 45

Body fat () 296 plusmn 95 275 plusmn 99

Int J Obesity 2005 29(3)281-6

Exposure to Ad36 was associated with

a) greater fat at baseline

b) greater increase in fat

Lin WY et al Diabetes Care Nov 2012

Serum samples of 1400 Mexican American individuals

Longitudinal study ndash 10 y follow up

Dhurandhar NV Lancet Inf Dis 2011 11963-69

USA

CA GA MD

MO (WI MI LA VA)

Canada Mexico

Korea China

Sweden Belgium

The Czech Republic

Italy Poland

Turkey

Australia

AD-36 STUDIES

Ad36 amp BMI

Ad36 amp Obesity

EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN

HUMANS

Obesity 2013 Jun 26 doi 101002oby20533

Serological data analyses show that adenovirus

36 infection is associated with obesity

A meta-analysis involving 5739 subjects

Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H

httpwwwflickrcomcamerassonydsc-w55

UNIVERSITY OF MUMBAI

Dhurandhar NV et al Vet Microbiol 1992 31 101-107

Dhurandhar NV et al Obesity Res 1997 5464-69

Dhurandhar NV et al J Bom Vet College 1990 2131-32

Chickens SMAM-1 increases adiposity amp reduced serum lipids

Obese Humans SMAM-1 is associated with greater BMI and lower lipids

AVIAN ADENOVIRUS SMAM-1 INCREASES BODY FAT

Adipogenic microbes 1 Canine Distemper Virus Lyons et al 1982

2 RAV-7 Carter et al 1983 3 Borna Disease Virus Gosztonyi et al 1985 4 Scrapie agents Kim et al 1987 5 Avian adenovirus SMAM-1 Dhurandhar et al 1992 6 Human adenovirus Ad36 Dhurandhar et al 1999

7 Human adenovirus Ad37 Atkinson et al 2005 8 Human adenovirus Ad5 So et al 2005 9 Gut microbiota in mice Backhed et al 2004 10 Protozoal parasites in Dragon Fly Schlider et al 2006 11 Chlamydia pneumoniae Dart et al 2002 12 Oral bacteria ndash selenomonas noxia Goodson et al 2009

0

20

40

60

80

100

o

be

se

Obesity Prevelance

Control

Ad36

Dhurandhar et al Int J Obes 200125990-996

Dhurandhar et al J Nutr 2002 1323155-3160

Dhurandhar et al Int J Obes 200024989-996

Pasarica et al Obesity 2006 14 (11) 1905-13

AD-36 INCREASES ADIPOSITY IN ANIMAL MODELS

0

5

10

15

20

25

30

35

40

45

0 2 4 6 8 10 12 14 16 18 20 22 24 26

Weeks post inoculation

We

igh

t c

ha

ng

e (

g)

Ad-36

Control

0

4

8

12

16

Total Body Fat ()

Ad-36

Control

Weight change Body fat

AD-36 INCREASES ADIPOSITY IN MARMOSETS

Virus-induced obesity

Mechanism of Action

STEM CELLS

ADIPOCYTE

PRE-

ADIPOCYTE

Mechanism of action of Ad36

Adipose tissue expansion by increasing proliferation

commitment differentiation and lipid accumulation in

adipocyte progenitors ASC

Virus-induced obesity

A causative role in humans

Challenges

1 Obesity has insidious onset

2 Multiple etiological factors ndash difficult to attribute to a factor

3 A combination of infection with other factors needed

4 Ethical reasons preclude experimental infection of humans

Do certain infections cause human obesity

Twin Study

Body weight of twins is similar

Hypothesis

Ad36 infected co-twins will be heavier compared

to uninfected co-twins

Twin pairs (n=26) discordant for Ad-36 antibodies

Antibody + Antibody -

Age (y) 330 plusmn 157 330 plusmn 157

Sex ( F M) 77 23 77 23

BMI (kgm2) 245 plusmn 52 231 plusmn 45

Body fat () 296 plusmn 95 275 plusmn 99

Int J Obesity 2005 29(3)281-6

Exposure to Ad36 was associated with

a) greater fat at baseline

b) greater increase in fat

Lin WY et al Diabetes Care Nov 2012

Serum samples of 1400 Mexican American individuals

Longitudinal study ndash 10 y follow up

Dhurandhar NV Lancet Inf Dis 2011 11963-69

USA

CA GA MD

MO (WI MI LA VA)

Canada Mexico

Korea China

Sweden Belgium

The Czech Republic

Italy Poland

Turkey

Australia

AD-36 STUDIES

Ad36 amp BMI

Ad36 amp Obesity

EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN

HUMANS

Obesity 2013 Jun 26 doi 101002oby20533

Serological data analyses show that adenovirus

36 infection is associated with obesity

A meta-analysis involving 5739 subjects

Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H

Dhurandhar NV et al Vet Microbiol 1992 31 101-107

Dhurandhar NV et al Obesity Res 1997 5464-69

Dhurandhar NV et al J Bom Vet College 1990 2131-32

Chickens SMAM-1 increases adiposity amp reduced serum lipids

Obese Humans SMAM-1 is associated with greater BMI and lower lipids

AVIAN ADENOVIRUS SMAM-1 INCREASES BODY FAT

Adipogenic microbes 1 Canine Distemper Virus Lyons et al 1982

2 RAV-7 Carter et al 1983 3 Borna Disease Virus Gosztonyi et al 1985 4 Scrapie agents Kim et al 1987 5 Avian adenovirus SMAM-1 Dhurandhar et al 1992 6 Human adenovirus Ad36 Dhurandhar et al 1999

7 Human adenovirus Ad37 Atkinson et al 2005 8 Human adenovirus Ad5 So et al 2005 9 Gut microbiota in mice Backhed et al 2004 10 Protozoal parasites in Dragon Fly Schlider et al 2006 11 Chlamydia pneumoniae Dart et al 2002 12 Oral bacteria ndash selenomonas noxia Goodson et al 2009

0

20

40

60

80

100

o

be

se

Obesity Prevelance

Control

Ad36

Dhurandhar et al Int J Obes 200125990-996

Dhurandhar et al J Nutr 2002 1323155-3160

Dhurandhar et al Int J Obes 200024989-996

Pasarica et al Obesity 2006 14 (11) 1905-13

AD-36 INCREASES ADIPOSITY IN ANIMAL MODELS

0

5

10

15

20

25

30

35

40

45

0 2 4 6 8 10 12 14 16 18 20 22 24 26

Weeks post inoculation

We

igh

t c

ha

ng

e (

g)

Ad-36

Control

0

4

8

12

16

Total Body Fat ()

Ad-36

Control

Weight change Body fat

AD-36 INCREASES ADIPOSITY IN MARMOSETS

Virus-induced obesity

Mechanism of Action

STEM CELLS

ADIPOCYTE

PRE-

ADIPOCYTE

Mechanism of action of Ad36

Adipose tissue expansion by increasing proliferation

commitment differentiation and lipid accumulation in

adipocyte progenitors ASC

Virus-induced obesity

A causative role in humans

Challenges

1 Obesity has insidious onset

2 Multiple etiological factors ndash difficult to attribute to a factor

3 A combination of infection with other factors needed

4 Ethical reasons preclude experimental infection of humans

Do certain infections cause human obesity

Twin Study

Body weight of twins is similar

Hypothesis

Ad36 infected co-twins will be heavier compared

to uninfected co-twins

Twin pairs (n=26) discordant for Ad-36 antibodies

Antibody + Antibody -

Age (y) 330 plusmn 157 330 plusmn 157

Sex ( F M) 77 23 77 23

BMI (kgm2) 245 plusmn 52 231 plusmn 45

Body fat () 296 plusmn 95 275 plusmn 99

Int J Obesity 2005 29(3)281-6

Exposure to Ad36 was associated with

a) greater fat at baseline

b) greater increase in fat

Lin WY et al Diabetes Care Nov 2012

Serum samples of 1400 Mexican American individuals

Longitudinal study ndash 10 y follow up

Dhurandhar NV Lancet Inf Dis 2011 11963-69

USA

CA GA MD

MO (WI MI LA VA)

Canada Mexico

Korea China

Sweden Belgium

The Czech Republic

Italy Poland

Turkey

Australia

AD-36 STUDIES

Ad36 amp BMI

Ad36 amp Obesity

EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN

HUMANS

Obesity 2013 Jun 26 doi 101002oby20533

Serological data analyses show that adenovirus

36 infection is associated with obesity

A meta-analysis involving 5739 subjects

Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H

Adipogenic microbes 1 Canine Distemper Virus Lyons et al 1982

2 RAV-7 Carter et al 1983 3 Borna Disease Virus Gosztonyi et al 1985 4 Scrapie agents Kim et al 1987 5 Avian adenovirus SMAM-1 Dhurandhar et al 1992 6 Human adenovirus Ad36 Dhurandhar et al 1999

7 Human adenovirus Ad37 Atkinson et al 2005 8 Human adenovirus Ad5 So et al 2005 9 Gut microbiota in mice Backhed et al 2004 10 Protozoal parasites in Dragon Fly Schlider et al 2006 11 Chlamydia pneumoniae Dart et al 2002 12 Oral bacteria ndash selenomonas noxia Goodson et al 2009

0

20

40

60

80

100

o

be

se

Obesity Prevelance

Control

Ad36

Dhurandhar et al Int J Obes 200125990-996

Dhurandhar et al J Nutr 2002 1323155-3160

Dhurandhar et al Int J Obes 200024989-996

Pasarica et al Obesity 2006 14 (11) 1905-13

AD-36 INCREASES ADIPOSITY IN ANIMAL MODELS

0

5

10

15

20

25

30

35

40

45

0 2 4 6 8 10 12 14 16 18 20 22 24 26

Weeks post inoculation

We

igh

t c

ha

ng

e (

g)

Ad-36

Control

0

4

8

12

16

Total Body Fat ()

Ad-36

Control

Weight change Body fat

AD-36 INCREASES ADIPOSITY IN MARMOSETS

Virus-induced obesity

Mechanism of Action

STEM CELLS

ADIPOCYTE

PRE-

ADIPOCYTE

Mechanism of action of Ad36

Adipose tissue expansion by increasing proliferation

commitment differentiation and lipid accumulation in

adipocyte progenitors ASC

Virus-induced obesity

A causative role in humans

Challenges

1 Obesity has insidious onset

2 Multiple etiological factors ndash difficult to attribute to a factor

3 A combination of infection with other factors needed

4 Ethical reasons preclude experimental infection of humans

Do certain infections cause human obesity

Twin Study

Body weight of twins is similar

Hypothesis

Ad36 infected co-twins will be heavier compared

to uninfected co-twins

Twin pairs (n=26) discordant for Ad-36 antibodies

Antibody + Antibody -

Age (y) 330 plusmn 157 330 plusmn 157

Sex ( F M) 77 23 77 23

BMI (kgm2) 245 plusmn 52 231 plusmn 45

Body fat () 296 plusmn 95 275 plusmn 99

Int J Obesity 2005 29(3)281-6

Exposure to Ad36 was associated with

a) greater fat at baseline

b) greater increase in fat

Lin WY et al Diabetes Care Nov 2012

Serum samples of 1400 Mexican American individuals

Longitudinal study ndash 10 y follow up

Dhurandhar NV Lancet Inf Dis 2011 11963-69

USA

CA GA MD

MO (WI MI LA VA)

Canada Mexico

Korea China

Sweden Belgium

The Czech Republic

Italy Poland

Turkey

Australia

AD-36 STUDIES

Ad36 amp BMI

Ad36 amp Obesity

EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN

HUMANS

Obesity 2013 Jun 26 doi 101002oby20533

Serological data analyses show that adenovirus

36 infection is associated with obesity

A meta-analysis involving 5739 subjects

Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H

0

20

40

60

80

100

o

be

se

Obesity Prevelance

Control

Ad36

Dhurandhar et al Int J Obes 200125990-996

Dhurandhar et al J Nutr 2002 1323155-3160

Dhurandhar et al Int J Obes 200024989-996

Pasarica et al Obesity 2006 14 (11) 1905-13

AD-36 INCREASES ADIPOSITY IN ANIMAL MODELS

0

5

10

15

20

25

30

35

40

45

0 2 4 6 8 10 12 14 16 18 20 22 24 26

Weeks post inoculation

We

igh

t c

ha

ng

e (

g)

Ad-36

Control

0

4

8

12

16

Total Body Fat ()

Ad-36

Control

Weight change Body fat

AD-36 INCREASES ADIPOSITY IN MARMOSETS

Virus-induced obesity

Mechanism of Action

STEM CELLS

ADIPOCYTE

PRE-

ADIPOCYTE

Mechanism of action of Ad36

Adipose tissue expansion by increasing proliferation

commitment differentiation and lipid accumulation in

adipocyte progenitors ASC

Virus-induced obesity

A causative role in humans

Challenges

1 Obesity has insidious onset

2 Multiple etiological factors ndash difficult to attribute to a factor

3 A combination of infection with other factors needed

4 Ethical reasons preclude experimental infection of humans

Do certain infections cause human obesity

Twin Study

Body weight of twins is similar

Hypothesis

Ad36 infected co-twins will be heavier compared

to uninfected co-twins

Twin pairs (n=26) discordant for Ad-36 antibodies

Antibody + Antibody -

Age (y) 330 plusmn 157 330 plusmn 157

Sex ( F M) 77 23 77 23

BMI (kgm2) 245 plusmn 52 231 plusmn 45

Body fat () 296 plusmn 95 275 plusmn 99

Int J Obesity 2005 29(3)281-6

Exposure to Ad36 was associated with

a) greater fat at baseline

b) greater increase in fat

Lin WY et al Diabetes Care Nov 2012

Serum samples of 1400 Mexican American individuals

Longitudinal study ndash 10 y follow up

Dhurandhar NV Lancet Inf Dis 2011 11963-69

USA

CA GA MD

MO (WI MI LA VA)

Canada Mexico

Korea China

Sweden Belgium

The Czech Republic

Italy Poland

Turkey

Australia

AD-36 STUDIES

Ad36 amp BMI

Ad36 amp Obesity

EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN

HUMANS

Obesity 2013 Jun 26 doi 101002oby20533

Serological data analyses show that adenovirus

36 infection is associated with obesity

A meta-analysis involving 5739 subjects

Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H

0

5

10

15

20

25

30

35

40

45

0 2 4 6 8 10 12 14 16 18 20 22 24 26

Weeks post inoculation

We

igh

t c

ha

ng

e (

g)

Ad-36

Control

0

4

8

12

16

Total Body Fat ()

Ad-36

Control

Weight change Body fat

AD-36 INCREASES ADIPOSITY IN MARMOSETS

Virus-induced obesity

Mechanism of Action

STEM CELLS

ADIPOCYTE

PRE-

ADIPOCYTE

Mechanism of action of Ad36

Adipose tissue expansion by increasing proliferation

commitment differentiation and lipid accumulation in

adipocyte progenitors ASC

Virus-induced obesity

A causative role in humans

Challenges

1 Obesity has insidious onset

2 Multiple etiological factors ndash difficult to attribute to a factor

3 A combination of infection with other factors needed

4 Ethical reasons preclude experimental infection of humans

Do certain infections cause human obesity

Twin Study

Body weight of twins is similar

Hypothesis

Ad36 infected co-twins will be heavier compared

to uninfected co-twins

Twin pairs (n=26) discordant for Ad-36 antibodies

Antibody + Antibody -

Age (y) 330 plusmn 157 330 plusmn 157

Sex ( F M) 77 23 77 23

BMI (kgm2) 245 plusmn 52 231 plusmn 45

Body fat () 296 plusmn 95 275 plusmn 99

Int J Obesity 2005 29(3)281-6

Exposure to Ad36 was associated with

a) greater fat at baseline

b) greater increase in fat

Lin WY et al Diabetes Care Nov 2012

Serum samples of 1400 Mexican American individuals

Longitudinal study ndash 10 y follow up

Dhurandhar NV Lancet Inf Dis 2011 11963-69

USA

CA GA MD

MO (WI MI LA VA)

Canada Mexico

Korea China

Sweden Belgium

The Czech Republic

Italy Poland

Turkey

Australia

AD-36 STUDIES

Ad36 amp BMI

Ad36 amp Obesity

EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN

HUMANS

Obesity 2013 Jun 26 doi 101002oby20533

Serological data analyses show that adenovirus

36 infection is associated with obesity

A meta-analysis involving 5739 subjects

Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H

Virus-induced obesity

Mechanism of Action

STEM CELLS

ADIPOCYTE

PRE-

ADIPOCYTE

Mechanism of action of Ad36

Adipose tissue expansion by increasing proliferation

commitment differentiation and lipid accumulation in

adipocyte progenitors ASC

Virus-induced obesity

A causative role in humans

Challenges

1 Obesity has insidious onset

2 Multiple etiological factors ndash difficult to attribute to a factor

3 A combination of infection with other factors needed

4 Ethical reasons preclude experimental infection of humans

Do certain infections cause human obesity

Twin Study

Body weight of twins is similar

Hypothesis

Ad36 infected co-twins will be heavier compared

to uninfected co-twins

Twin pairs (n=26) discordant for Ad-36 antibodies

Antibody + Antibody -

Age (y) 330 plusmn 157 330 plusmn 157

Sex ( F M) 77 23 77 23

BMI (kgm2) 245 plusmn 52 231 plusmn 45

Body fat () 296 plusmn 95 275 plusmn 99

Int J Obesity 2005 29(3)281-6

Exposure to Ad36 was associated with

a) greater fat at baseline

b) greater increase in fat

Lin WY et al Diabetes Care Nov 2012

Serum samples of 1400 Mexican American individuals

Longitudinal study ndash 10 y follow up

Dhurandhar NV Lancet Inf Dis 2011 11963-69

USA

CA GA MD

MO (WI MI LA VA)

Canada Mexico

Korea China

Sweden Belgium

The Czech Republic

Italy Poland

Turkey

Australia

AD-36 STUDIES

Ad36 amp BMI

Ad36 amp Obesity

EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN

HUMANS

Obesity 2013 Jun 26 doi 101002oby20533

Serological data analyses show that adenovirus

36 infection is associated with obesity

A meta-analysis involving 5739 subjects

Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H

STEM CELLS

ADIPOCYTE

PRE-

ADIPOCYTE

Mechanism of action of Ad36

Adipose tissue expansion by increasing proliferation

commitment differentiation and lipid accumulation in

adipocyte progenitors ASC

Virus-induced obesity

A causative role in humans

Challenges

1 Obesity has insidious onset

2 Multiple etiological factors ndash difficult to attribute to a factor

3 A combination of infection with other factors needed

4 Ethical reasons preclude experimental infection of humans

Do certain infections cause human obesity

Twin Study

Body weight of twins is similar

Hypothesis

Ad36 infected co-twins will be heavier compared

to uninfected co-twins

Twin pairs (n=26) discordant for Ad-36 antibodies

Antibody + Antibody -

Age (y) 330 plusmn 157 330 plusmn 157

Sex ( F M) 77 23 77 23

BMI (kgm2) 245 plusmn 52 231 plusmn 45

Body fat () 296 plusmn 95 275 plusmn 99

Int J Obesity 2005 29(3)281-6

Exposure to Ad36 was associated with

a) greater fat at baseline

b) greater increase in fat

Lin WY et al Diabetes Care Nov 2012

Serum samples of 1400 Mexican American individuals

Longitudinal study ndash 10 y follow up

Dhurandhar NV Lancet Inf Dis 2011 11963-69

USA

CA GA MD

MO (WI MI LA VA)

Canada Mexico

Korea China

Sweden Belgium

The Czech Republic

Italy Poland

Turkey

Australia

AD-36 STUDIES

Ad36 amp BMI

Ad36 amp Obesity

EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN

HUMANS

Obesity 2013 Jun 26 doi 101002oby20533

Serological data analyses show that adenovirus

36 infection is associated with obesity

A meta-analysis involving 5739 subjects

Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H

Virus-induced obesity

A causative role in humans

Challenges

1 Obesity has insidious onset

2 Multiple etiological factors ndash difficult to attribute to a factor

3 A combination of infection with other factors needed

4 Ethical reasons preclude experimental infection of humans

Do certain infections cause human obesity

Twin Study

Body weight of twins is similar

Hypothesis

Ad36 infected co-twins will be heavier compared

to uninfected co-twins

Twin pairs (n=26) discordant for Ad-36 antibodies

Antibody + Antibody -

Age (y) 330 plusmn 157 330 plusmn 157

Sex ( F M) 77 23 77 23

BMI (kgm2) 245 plusmn 52 231 plusmn 45

Body fat () 296 plusmn 95 275 plusmn 99

Int J Obesity 2005 29(3)281-6

Exposure to Ad36 was associated with

a) greater fat at baseline

b) greater increase in fat

Lin WY et al Diabetes Care Nov 2012

Serum samples of 1400 Mexican American individuals

Longitudinal study ndash 10 y follow up

Dhurandhar NV Lancet Inf Dis 2011 11963-69

USA

CA GA MD

MO (WI MI LA VA)

Canada Mexico

Korea China

Sweden Belgium

The Czech Republic

Italy Poland

Turkey

Australia

AD-36 STUDIES

Ad36 amp BMI

Ad36 amp Obesity

EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN

HUMANS

Obesity 2013 Jun 26 doi 101002oby20533

Serological data analyses show that adenovirus

36 infection is associated with obesity

A meta-analysis involving 5739 subjects

Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H

Challenges

1 Obesity has insidious onset

2 Multiple etiological factors ndash difficult to attribute to a factor

3 A combination of infection with other factors needed

4 Ethical reasons preclude experimental infection of humans

Do certain infections cause human obesity

Twin Study

Body weight of twins is similar

Hypothesis

Ad36 infected co-twins will be heavier compared

to uninfected co-twins

Twin pairs (n=26) discordant for Ad-36 antibodies

Antibody + Antibody -

Age (y) 330 plusmn 157 330 plusmn 157

Sex ( F M) 77 23 77 23

BMI (kgm2) 245 plusmn 52 231 plusmn 45

Body fat () 296 plusmn 95 275 plusmn 99

Int J Obesity 2005 29(3)281-6

Exposure to Ad36 was associated with

a) greater fat at baseline

b) greater increase in fat

Lin WY et al Diabetes Care Nov 2012

Serum samples of 1400 Mexican American individuals

Longitudinal study ndash 10 y follow up

Dhurandhar NV Lancet Inf Dis 2011 11963-69

USA

CA GA MD

MO (WI MI LA VA)

Canada Mexico

Korea China

Sweden Belgium

The Czech Republic

Italy Poland

Turkey

Australia

AD-36 STUDIES

Ad36 amp BMI

Ad36 amp Obesity

EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN

HUMANS

Obesity 2013 Jun 26 doi 101002oby20533

Serological data analyses show that adenovirus

36 infection is associated with obesity

A meta-analysis involving 5739 subjects

Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H

Twin Study

Body weight of twins is similar

Hypothesis

Ad36 infected co-twins will be heavier compared

to uninfected co-twins

Twin pairs (n=26) discordant for Ad-36 antibodies

Antibody + Antibody -

Age (y) 330 plusmn 157 330 plusmn 157

Sex ( F M) 77 23 77 23

BMI (kgm2) 245 plusmn 52 231 plusmn 45

Body fat () 296 plusmn 95 275 plusmn 99

Int J Obesity 2005 29(3)281-6

Exposure to Ad36 was associated with

a) greater fat at baseline

b) greater increase in fat

Lin WY et al Diabetes Care Nov 2012

Serum samples of 1400 Mexican American individuals

Longitudinal study ndash 10 y follow up

Dhurandhar NV Lancet Inf Dis 2011 11963-69

USA

CA GA MD

MO (WI MI LA VA)

Canada Mexico

Korea China

Sweden Belgium

The Czech Republic

Italy Poland

Turkey

Australia

AD-36 STUDIES

Ad36 amp BMI

Ad36 amp Obesity

EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN

HUMANS

Obesity 2013 Jun 26 doi 101002oby20533

Serological data analyses show that adenovirus

36 infection is associated with obesity

A meta-analysis involving 5739 subjects

Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H

Twin pairs (n=26) discordant for Ad-36 antibodies

Antibody + Antibody -

Age (y) 330 plusmn 157 330 plusmn 157

Sex ( F M) 77 23 77 23

BMI (kgm2) 245 plusmn 52 231 plusmn 45

Body fat () 296 plusmn 95 275 plusmn 99

Int J Obesity 2005 29(3)281-6

Exposure to Ad36 was associated with

a) greater fat at baseline

b) greater increase in fat

Lin WY et al Diabetes Care Nov 2012

Serum samples of 1400 Mexican American individuals

Longitudinal study ndash 10 y follow up

Dhurandhar NV Lancet Inf Dis 2011 11963-69

USA

CA GA MD

MO (WI MI LA VA)

Canada Mexico

Korea China

Sweden Belgium

The Czech Republic

Italy Poland

Turkey

Australia

AD-36 STUDIES

Ad36 amp BMI

Ad36 amp Obesity

EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN

HUMANS

Obesity 2013 Jun 26 doi 101002oby20533

Serological data analyses show that adenovirus

36 infection is associated with obesity

A meta-analysis involving 5739 subjects

Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H

Exposure to Ad36 was associated with

a) greater fat at baseline

b) greater increase in fat

Lin WY et al Diabetes Care Nov 2012

Serum samples of 1400 Mexican American individuals

Longitudinal study ndash 10 y follow up

Dhurandhar NV Lancet Inf Dis 2011 11963-69

USA

CA GA MD

MO (WI MI LA VA)

Canada Mexico

Korea China

Sweden Belgium

The Czech Republic

Italy Poland

Turkey

Australia

AD-36 STUDIES

Ad36 amp BMI

Ad36 amp Obesity

EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN

HUMANS

Obesity 2013 Jun 26 doi 101002oby20533

Serological data analyses show that adenovirus

36 infection is associated with obesity

A meta-analysis involving 5739 subjects

Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H

Dhurandhar NV Lancet Inf Dis 2011 11963-69

USA

CA GA MD

MO (WI MI LA VA)

Canada Mexico

Korea China

Sweden Belgium

The Czech Republic

Italy Poland

Turkey

Australia

AD-36 STUDIES

Ad36 amp BMI

Ad36 amp Obesity

EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN

HUMANS

Obesity 2013 Jun 26 doi 101002oby20533

Serological data analyses show that adenovirus

36 infection is associated with obesity

A meta-analysis involving 5739 subjects

Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H

USA

CA GA MD

MO (WI MI LA VA)

Canada Mexico

Korea China

Sweden Belgium

The Czech Republic

Italy Poland

Turkey

Australia

AD-36 STUDIES

Ad36 amp BMI

Ad36 amp Obesity

EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN

HUMANS

Obesity 2013 Jun 26 doi 101002oby20533

Serological data analyses show that adenovirus

36 infection is associated with obesity

A meta-analysis involving 5739 subjects

Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H

Ad36 amp BMI

Ad36 amp Obesity

EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN

HUMANS

Obesity 2013 Jun 26 doi 101002oby20533

Serological data analyses show that adenovirus

36 infection is associated with obesity

A meta-analysis involving 5739 subjects

Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H

EXPOSURE TO AD36 IS ASSOCIATED WITH OBESITY IN

HUMANS

Obesity 2013 Jun 26 doi 101002oby20533

Serological data analyses show that adenovirus

36 infection is associated with obesity

A meta-analysis involving 5739 subjects

Shang Q Wang H Song Y Wei L Lavebratt C Zhang F Gu H

Virus-induced obesity

Implications

Obesity Prevention amp

Treatment

Na amp Nam JID 2012 205914

C57BL6 mice WT vs MCP1 KO mice

Ad36 up-regulates inflammatory cytokines in vivo

Microbiol Immunol 2014 Mar 2 doi 1011111348-042112146 [Epub

ahead of print]

Reduction of adenovirus 36-induced obesity and inflammation via the

use of mulberry extract

Na HN1 Park S Jeon HJ Kim HB Nam JH

Mulberry extract reduces inflammation and Ad36-induced obesity

Treatment of Ad36-induced obesity

Obesity Prevention amp

Treatment

Na amp Nam JID 2012 205914

C57BL6 mice WT vs MCP1 KO mice

Ad36 up-regulates inflammatory cytokines in vivo

Microbiol Immunol 2014 Mar 2 doi 1011111348-042112146 [Epub

ahead of print]

Reduction of adenovirus 36-induced obesity and inflammation via the

use of mulberry extract

Na HN1 Park S Jeon HJ Kim HB Nam JH

Mulberry extract reduces inflammation and Ad36-induced obesity

Treatment of Ad36-induced obesity

Na amp Nam JID 2012 205914

C57BL6 mice WT vs MCP1 KO mice

Ad36 up-regulates inflammatory cytokines in vivo

Microbiol Immunol 2014 Mar 2 doi 1011111348-042112146 [Epub

ahead of print]

Reduction of adenovirus 36-induced obesity and inflammation via the

use of mulberry extract

Na HN1 Park S Jeon HJ Kim HB Nam JH

Mulberry extract reduces inflammation and Ad36-induced obesity

Treatment of Ad36-induced obesity

Microbiol Immunol 2014 Mar 2 doi 1011111348-042112146 [Epub

ahead of print]

Reduction of adenovirus 36-induced obesity and inflammation via the

use of mulberry extract

Na HN1 Park S Jeon HJ Kim HB Nam JH

Mulberry extract reduces inflammation and Ad36-induced obesity

Treatment of Ad36-induced obesity

Prevention of Ad36-induced obesity

SUMMARY amp CONCLUSION

OBESITY

SUMMARY amp CONCLUSION

OBESITIES

SUMMARY amp CONCLUSION

OBESITIES

Unique prevention amp treatment strategies for

Ad36-induced obesity

Other adipogenic pathogens

other types of ldquoobesitiesrdquo

A United States Patents approved

1 Number 6127113 Viral Obesity methods and Compositions

2 Number 6664050 Viral Obesity methods and Compositions

3 Number US 8008436B2 Adenovirus 36 E4orf1 gene amp protein amp their uses

B Patents filed

1 Adenovirus Ad36 E4orf1 protein for prevention and treatment of non-alcoholic

fatty liver disease US patent application 61362443 Taiwan Patent number

100124173

2 Enhanced glycemic control using Ad36E4orf1 and AKT1 inhibitor

C Provisional patent filed

1 Compositions and methods for improving glucose uptake

PATENTS

National Institutes of Health

American Diabetes Association

Federal Emergency Management Agency

American Egg Board

The Mathile Institute

Vital Health Interventions

Kellogg

Genentech

Novartis

Hoffman La Roche

Lei Cao Ohio State University NIH 121CA178227-01

Rena S Day University of Texas FEMA

Melinda Sothern NIH R01

Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal

Jae-Hwan Nam South Korea - proposal

COLLABORATIVE GRANTS ndash AD36 E4orf1

Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD

Sharada Vangipuram PhD

Minghuan Yu MD PhD

Bhavani Krishnan MS

Mitali Kapila MS

John Sheele MS

Magdalena Pasarica MD PhD

Miloni Rathod MS

Pamela Rogers MS

Scott Loiler PhD

Nazar Mashtalir

Olga Dubuisson MD PhD

Emily McAllister

Rashmi Krishnapuram PhD

Heather Kirk-Ballard MS

COLLABORATORS CONTRIBUTORS

Paige Kennedy

Olga Dubuisson MD PhD Rashmi Krishnapuram PhD

Grant Williams

SooHo Park

Ha-Na Na PhD

Jae-Hwan Nam PhD

Vijay Hegde PhD

Cathy Huey

INFECTIONS AND OBESITY LABORATORY

Batu Caves

Malaysia March 2014

Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice

TNFα MCP1

Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89

SUMMARY amp CONCLUSION

OBESITY

SUMMARY amp CONCLUSION

OBESITIES

SUMMARY amp CONCLUSION

OBESITIES

Unique prevention amp treatment strategies for

Ad36-induced obesity

Other adipogenic pathogens

other types of ldquoobesitiesrdquo

A United States Patents approved

1 Number 6127113 Viral Obesity methods and Compositions

2 Number 6664050 Viral Obesity methods and Compositions

3 Number US 8008436B2 Adenovirus 36 E4orf1 gene amp protein amp their uses

B Patents filed

1 Adenovirus Ad36 E4orf1 protein for prevention and treatment of non-alcoholic

fatty liver disease US patent application 61362443 Taiwan Patent number

100124173

2 Enhanced glycemic control using Ad36E4orf1 and AKT1 inhibitor

C Provisional patent filed

1 Compositions and methods for improving glucose uptake

PATENTS

National Institutes of Health

American Diabetes Association

Federal Emergency Management Agency

American Egg Board

The Mathile Institute

Vital Health Interventions

Kellogg

Genentech

Novartis

Hoffman La Roche

Lei Cao Ohio State University NIH 121CA178227-01

Rena S Day University of Texas FEMA

Melinda Sothern NIH R01

Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal

Jae-Hwan Nam South Korea - proposal

COLLABORATIVE GRANTS ndash AD36 E4orf1

Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD

Sharada Vangipuram PhD

Minghuan Yu MD PhD

Bhavani Krishnan MS

Mitali Kapila MS

John Sheele MS

Magdalena Pasarica MD PhD

Miloni Rathod MS

Pamela Rogers MS

Scott Loiler PhD

Nazar Mashtalir

Olga Dubuisson MD PhD

Emily McAllister

Rashmi Krishnapuram PhD

Heather Kirk-Ballard MS

COLLABORATORS CONTRIBUTORS

Paige Kennedy

Olga Dubuisson MD PhD Rashmi Krishnapuram PhD

Grant Williams

SooHo Park

Ha-Na Na PhD

Jae-Hwan Nam PhD

Vijay Hegde PhD

Cathy Huey

INFECTIONS AND OBESITY LABORATORY

Batu Caves

Malaysia March 2014

Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice

TNFα MCP1

Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89

SUMMARY amp CONCLUSION

OBESITIES

SUMMARY amp CONCLUSION

OBESITIES

Unique prevention amp treatment strategies for

Ad36-induced obesity

Other adipogenic pathogens

other types of ldquoobesitiesrdquo

A United States Patents approved

1 Number 6127113 Viral Obesity methods and Compositions

2 Number 6664050 Viral Obesity methods and Compositions

3 Number US 8008436B2 Adenovirus 36 E4orf1 gene amp protein amp their uses

B Patents filed

1 Adenovirus Ad36 E4orf1 protein for prevention and treatment of non-alcoholic

fatty liver disease US patent application 61362443 Taiwan Patent number

100124173

2 Enhanced glycemic control using Ad36E4orf1 and AKT1 inhibitor

C Provisional patent filed

1 Compositions and methods for improving glucose uptake

PATENTS

National Institutes of Health

American Diabetes Association

Federal Emergency Management Agency

American Egg Board

The Mathile Institute

Vital Health Interventions

Kellogg

Genentech

Novartis

Hoffman La Roche

Lei Cao Ohio State University NIH 121CA178227-01

Rena S Day University of Texas FEMA

Melinda Sothern NIH R01

Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal

Jae-Hwan Nam South Korea - proposal

COLLABORATIVE GRANTS ndash AD36 E4orf1

Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD

Sharada Vangipuram PhD

Minghuan Yu MD PhD

Bhavani Krishnan MS

Mitali Kapila MS

John Sheele MS

Magdalena Pasarica MD PhD

Miloni Rathod MS

Pamela Rogers MS

Scott Loiler PhD

Nazar Mashtalir

Olga Dubuisson MD PhD

Emily McAllister

Rashmi Krishnapuram PhD

Heather Kirk-Ballard MS

COLLABORATORS CONTRIBUTORS

Paige Kennedy

Olga Dubuisson MD PhD Rashmi Krishnapuram PhD

Grant Williams

SooHo Park

Ha-Na Na PhD

Jae-Hwan Nam PhD

Vijay Hegde PhD

Cathy Huey

INFECTIONS AND OBESITY LABORATORY

Batu Caves

Malaysia March 2014

Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice

TNFα MCP1

Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89

SUMMARY amp CONCLUSION

OBESITIES

Unique prevention amp treatment strategies for

Ad36-induced obesity

Other adipogenic pathogens

other types of ldquoobesitiesrdquo

A United States Patents approved

1 Number 6127113 Viral Obesity methods and Compositions

2 Number 6664050 Viral Obesity methods and Compositions

3 Number US 8008436B2 Adenovirus 36 E4orf1 gene amp protein amp their uses

B Patents filed

1 Adenovirus Ad36 E4orf1 protein for prevention and treatment of non-alcoholic

fatty liver disease US patent application 61362443 Taiwan Patent number

100124173

2 Enhanced glycemic control using Ad36E4orf1 and AKT1 inhibitor

C Provisional patent filed

1 Compositions and methods for improving glucose uptake

PATENTS

National Institutes of Health

American Diabetes Association

Federal Emergency Management Agency

American Egg Board

The Mathile Institute

Vital Health Interventions

Kellogg

Genentech

Novartis

Hoffman La Roche

Lei Cao Ohio State University NIH 121CA178227-01

Rena S Day University of Texas FEMA

Melinda Sothern NIH R01

Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal

Jae-Hwan Nam South Korea - proposal

COLLABORATIVE GRANTS ndash AD36 E4orf1

Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD

Sharada Vangipuram PhD

Minghuan Yu MD PhD

Bhavani Krishnan MS

Mitali Kapila MS

John Sheele MS

Magdalena Pasarica MD PhD

Miloni Rathod MS

Pamela Rogers MS

Scott Loiler PhD

Nazar Mashtalir

Olga Dubuisson MD PhD

Emily McAllister

Rashmi Krishnapuram PhD

Heather Kirk-Ballard MS

COLLABORATORS CONTRIBUTORS

Paige Kennedy

Olga Dubuisson MD PhD Rashmi Krishnapuram PhD

Grant Williams

SooHo Park

Ha-Na Na PhD

Jae-Hwan Nam PhD

Vijay Hegde PhD

Cathy Huey

INFECTIONS AND OBESITY LABORATORY

Batu Caves

Malaysia March 2014

Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice

TNFα MCP1

Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89

A United States Patents approved

1 Number 6127113 Viral Obesity methods and Compositions

2 Number 6664050 Viral Obesity methods and Compositions

3 Number US 8008436B2 Adenovirus 36 E4orf1 gene amp protein amp their uses

B Patents filed

1 Adenovirus Ad36 E4orf1 protein for prevention and treatment of non-alcoholic

fatty liver disease US patent application 61362443 Taiwan Patent number

100124173

2 Enhanced glycemic control using Ad36E4orf1 and AKT1 inhibitor

C Provisional patent filed

1 Compositions and methods for improving glucose uptake

PATENTS

National Institutes of Health

American Diabetes Association

Federal Emergency Management Agency

American Egg Board

The Mathile Institute

Vital Health Interventions

Kellogg

Genentech

Novartis

Hoffman La Roche

Lei Cao Ohio State University NIH 121CA178227-01

Rena S Day University of Texas FEMA

Melinda Sothern NIH R01

Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal

Jae-Hwan Nam South Korea - proposal

COLLABORATIVE GRANTS ndash AD36 E4orf1

Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD

Sharada Vangipuram PhD

Minghuan Yu MD PhD

Bhavani Krishnan MS

Mitali Kapila MS

John Sheele MS

Magdalena Pasarica MD PhD

Miloni Rathod MS

Pamela Rogers MS

Scott Loiler PhD

Nazar Mashtalir

Olga Dubuisson MD PhD

Emily McAllister

Rashmi Krishnapuram PhD

Heather Kirk-Ballard MS

COLLABORATORS CONTRIBUTORS

Paige Kennedy

Olga Dubuisson MD PhD Rashmi Krishnapuram PhD

Grant Williams

SooHo Park

Ha-Na Na PhD

Jae-Hwan Nam PhD

Vijay Hegde PhD

Cathy Huey

INFECTIONS AND OBESITY LABORATORY

Batu Caves

Malaysia March 2014

Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice

TNFα MCP1

Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89

National Institutes of Health

American Diabetes Association

Federal Emergency Management Agency

American Egg Board

The Mathile Institute

Vital Health Interventions

Kellogg

Genentech

Novartis

Hoffman La Roche

Lei Cao Ohio State University NIH 121CA178227-01

Rena S Day University of Texas FEMA

Melinda Sothern NIH R01

Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal

Jae-Hwan Nam South Korea - proposal

COLLABORATIVE GRANTS ndash AD36 E4orf1

Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD

Sharada Vangipuram PhD

Minghuan Yu MD PhD

Bhavani Krishnan MS

Mitali Kapila MS

John Sheele MS

Magdalena Pasarica MD PhD

Miloni Rathod MS

Pamela Rogers MS

Scott Loiler PhD

Nazar Mashtalir

Olga Dubuisson MD PhD

Emily McAllister

Rashmi Krishnapuram PhD

Heather Kirk-Ballard MS

COLLABORATORS CONTRIBUTORS

Paige Kennedy

Olga Dubuisson MD PhD Rashmi Krishnapuram PhD

Grant Williams

SooHo Park

Ha-Na Na PhD

Jae-Hwan Nam PhD

Vijay Hegde PhD

Cathy Huey

INFECTIONS AND OBESITY LABORATORY

Batu Caves

Malaysia March 2014

Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice

TNFα MCP1

Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89

Lei Cao Ohio State University NIH 121CA178227-01

Rena S Day University of Texas FEMA

Melinda Sothern NIH R01

Jonathan Shaw Baker IDI Heart Institute Australia ndash NHMRC - proposal

Jae-Hwan Nam South Korea - proposal

COLLABORATIVE GRANTS ndash AD36 E4orf1

Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD

Sharada Vangipuram PhD

Minghuan Yu MD PhD

Bhavani Krishnan MS

Mitali Kapila MS

John Sheele MS

Magdalena Pasarica MD PhD

Miloni Rathod MS

Pamela Rogers MS

Scott Loiler PhD

Nazar Mashtalir

Olga Dubuisson MD PhD

Emily McAllister

Rashmi Krishnapuram PhD

Heather Kirk-Ballard MS

COLLABORATORS CONTRIBUTORS

Paige Kennedy

Olga Dubuisson MD PhD Rashmi Krishnapuram PhD

Grant Williams

SooHo Park

Ha-Na Na PhD

Jae-Hwan Nam PhD

Vijay Hegde PhD

Cathy Huey

INFECTIONS AND OBESITY LABORATORY

Batu Caves

Malaysia March 2014

Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice

TNFα MCP1

Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89

Richard Atkinson MD Barbara Israel PhD Thomas Holland PhD David Allison PhD David Abbott PhD Joseph Kemnitz PhD Peter Havel PhD Juraj Koska MD Paska Permana PhD Phil Scherer PhD Ronald Javier PhD Melinda Sothern PhD Nancy Butte PhD Claude Bouchard PhD William Cefalu MD Jeff Gimble MD PhD Frank Greenway MD Alok Gupta MD William JohnsonPhD Cedric Moro PhD Eric Ravussin PhD Zhong Wang MD Jianping Ye MD Aamir Zuberi PhD Elizabeth Floyd PhD Sita Aggarwal PhD

Sharada Vangipuram PhD

Minghuan Yu MD PhD

Bhavani Krishnan MS

Mitali Kapila MS

John Sheele MS

Magdalena Pasarica MD PhD

Miloni Rathod MS

Pamela Rogers MS

Scott Loiler PhD

Nazar Mashtalir

Olga Dubuisson MD PhD

Emily McAllister

Rashmi Krishnapuram PhD

Heather Kirk-Ballard MS

COLLABORATORS CONTRIBUTORS

Paige Kennedy

Olga Dubuisson MD PhD Rashmi Krishnapuram PhD

Grant Williams

SooHo Park

Ha-Na Na PhD

Jae-Hwan Nam PhD

Vijay Hegde PhD

Cathy Huey

INFECTIONS AND OBESITY LABORATORY

Batu Caves

Malaysia March 2014

Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice

TNFα MCP1

Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89

Paige Kennedy

Olga Dubuisson MD PhD Rashmi Krishnapuram PhD

Grant Williams

SooHo Park

Ha-Na Na PhD

Jae-Hwan Nam PhD

Vijay Hegde PhD

Cathy Huey

INFECTIONS AND OBESITY LABORATORY

Batu Caves

Malaysia March 2014

Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice

TNFα MCP1

Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89

Batu Caves

Malaysia March 2014

Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice

TNFα MCP1

Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89

Ad36 increases inflammatory cytokines mRNA in adipose tissue of mice

TNFα MCP1

Krishnapuram et al Am J Physiology Endocrin Metab 2011300(5)E779-89