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By Yuji Matsuzawa, MD, PhD, Director, Professor Emeritus Osaka University, Somitomo Hospital, Osaka, Japan.
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Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org
Metabolic Syndrome and Adipose Tissue
Yuji Matsuzawa, MD, PhDDirector and Professor Emeritus
Osaka University, Sumitomo Hospital, Osaka, Japan
Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org
A Novel Technique for the Determination of Body Fat by Computed Tomography
From Tokunaga K et al. Int J Obes 1983; 7: 437-45Reproduced with permission
Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org
Visceral Fat Accumulation is an Important Determinant of Metabolic and Cardiovascular Disease
Insulin Resistance
Type 2 DiabetesDyslipidemia
Left VentricularDysfunctionYamashita S et al.
Diabetes Care 1996; 19: 287-91
Fujioka S et al. Metabolism 1987; 36: 54-9
Nakajima T et al. Am J Cardiol 1989; 64: 369-73
Kanai H et al. Hypertension 1990; 16: 484-90Kanai H et al. Hypertension 1996; 27: 125-9
Hypertension
Coronary Artery Disease
Sleep Apnea Syndrome
Nakamura T et al. Int J Obes Relat Metab Disord 1997; 21: 580-6Nakamura T et al. Atherosclerosis 1994; 107: 239-46
Shinohara E et al. J Intern Med 1997; 241: 11-8
Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org
Visceral Fat
Subcutaneous Fat
Rib
os
om
al
pro
tein
s
Sec
reto
ryp
rote
ins
Cyt
op
lasm
ic
pro
tein
s
Nu
clea
r p
rote
ins
Mem
bra
ne
pro
tein
s
Cyt
os
kele
ton
pro
tein
s
Sig
nal
tran
sdu
ctio
n
En
erg
yp
rod
uct
ion
Mit
och
on
dri
alp
rote
ins
Growth factorsCytokinesComplement factorsetc.
30
20
10
0Fre
qu
en
cy (
%)
30
20
10
0
Fre
qu
en
cy (
%)
Gene Expression Profile of Human Adipose Tissue
Adapted from Matsuzawa Y et al. Arterioscler Thromb Vasc Biol 2004; 24: 29-33Reproduced with permission
Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org
Enhanced Expression of PAI-1 in Visceral Fat
From Shimomura I et al. Nat Med 1996; 2: 800-3Reproduced with permission
PAI-1: plasminogen activator inhibitor-1
Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org
Decreased Plasma Adiponectin in Visceral Obesity
80
60
0 100 200 300
Plasma PAI-1
40
20
0
Visceral Fat Area (cm2)
ng/ml
0 100 200
Visceral Fat Area (cm2)
20
0
5
10
15
g/ml
Plasma adiponectin
300
PAI-1: plasminogen activator inhibitor-1
Adapted from Matsuzawa Y et al.Arterioscler Thromb Vasc Biol 2004; 24: 29-33
Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org
Plasma Adiponectin Levels
Relative Risk
Low High
1.0
2.1
Case-Control Study(CAD prevalence)
Adiponectin, an Independent Risk Factor of Coronary Artery Disease (CAD)
Adapted from Pischon T et al. JAMA 2004; 291: 1730-7
1.0
0.7
Relative Risk
Low High
Prospective Study(myocardial infarction
development)
Adapted from Kumada M et al. Arterioscler Thromb Vasc Biol 2003; 23: 85-9
Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org
Effect of Adiponectin on Vascular Cells
0
1
2
3
4
5
Adiponectin
NF-B
VC
AM
-1
mR
NA
0
1
2
3
4
p-ERK
Cel
l P
rolif
erat
ion
PDGF-BB 10 ng/ml
0
50
100
Scavenger Receptor
Cho
lest
eryl
E
ster
(%
)
EndothelialCells
SmoothMuscle Cells
Macrophages
- + - + - +
VCAM-1: vascular cell adhesion molecule-1NF-B: nuclear transcription factor-Bp-ERK: p-extracellular signal-related kinasePDGF-BB: platelet-derived growth factor-BB
Adiponectin Adiponectin
Adapted from Ouchi N et al. Circulation 2000; 102: 1296-301
Adapted from Arita Y et al. Circulation 2002; 105: 2893-8
Adapted from Ouchi N et al. Circulation 2001; 103: 1057-63
Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org
Endothelial Cells
Adipose Tissue
SmoothMuscle Cells
Mechanisms of Anti-atherogenicity of Adiponectin
Adapted from Matsuzawa Y et al. Arterioscler Thromb Vasc Biol 2004; 24: 29-33
Adhesion Molecules
Plaque Rupture
Macrophages
v
v
v
Adiponectin
TIMP-1
TNF-HB-EGF
Monocyte
TNF-: tumor necrosis factor-TIMP-1: tissue inhibitor of metalloproteinase-1HB-EGF: heparin-binding EGF-like growth factor
Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org
Hypo-adiponectinemia
Visceral Fat Accumulation
GeneticVariations
Type 2 Diabetes
Hypertension
Atherosclerosis
Cardiac Dysfunction
Non-alcoholic steatohepatitis
Cancers
Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org
www.cardiometabolic-risk.org
