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High-Fat Diets: Exploring the Nuances of Animal Studies and their

Translation to Human Outcomes

Craig H Warden, PhDProfessorUC Davis

chwarden@ucdavis.eduOffice phone 530 752 4187

Recent news media titles based on high fat diet studies in mice• (1) Blocking Single Gene Prevents Obesity in Fat-Fed Mice

– Daily update ⋅May 4, 2018 Genetic Engineering & Biotechnology News– European Scientist May 5, 2018– https://www.europeanscientist.com/en/research/researchers-prevent-

obesity-in-mice-fed-fatty-foods/• (2) How obesity makes it harder to taste

– Daily update ⋅March 21, 2018 Science News– NPR March 20, 2018

https://www.npr.org/sections/thesalt/2018/03/20/595237542/taste-buds-dull-as-people-gain-weight-now-scientists-think-they-know-why

– NY Post March 20– https://nypost.com/2018/03/20/obesity-robs-the-tongue-of-taste-buds-

study-says/• (3) Dietary fat, changes in fat metabolism may promote prostate

cancer metastasis– Daily update ⋅ January 15, 2018 Medical Xpress– Prostate Cancer News Today JANUARY 22, 2018– New York Times Jan 16, 2018 Link to article: – https://www.nytimes.com/2018/01/16/health/fat-diet-prostate-cancer.html

• The problem – how do we know if these results apply to humans?

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Methods for diet studies in mice• Ideal: – Compare two diets with identical ingredients that differ

in relative amounts – for instance varying amounts of fat and carbohydrate. A small minority do this.

• However, typical methods are:– compare a complex grain based chow diet to a purified

ingredient high-fat high-sucrose diet. These have no ingredients in common, but authors and press releases always blame fat for any bad outcomes.

• Even worse methods are common:– Many papers provide no information at all on the

ingredients used for a diet study.

Grain based diets• GB diets, which are often and unfortunately referred to

vaguely as “normal chow”, “normal diet” or “standard diet” in most publications, are made with grain and cereal ingredients and animal by-products.

• These unrefined ingredients include ‘ground corn’, ‘ground wheat’, ‘ground oats’, ‘fish meal’, ‘alfalfa meal’, ‘brewers dried yeast’ and ‘animal fat preserved with BHA’.

• These ingredients contain multiple nutrients and non-nutrients, and their inclusion level in GB diets (i.e. the formula) is not only ‘closed’ (kept secret from the research community) as it is considered proprietary, but the formula itself may vary over time depending on changes in nutrient levels in key ingredients.

•

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Purified diets

• The typical mouse purified diet contains protein from casein, carbohydrate from sucrose and maltose (no corn starch), and fats from lard, soy or corn oil (no fish oil).Cellulose is usually the only fiber.

Typical sources of nutrients and non-nutrients in rodent purified ingredient diets and grain-based diets

‘animal fat preserved with BHA’. These ingredients con-tain multiple nutrients and non-nutrients, and their inclu-sion level in GB diets (i.e. the formula) is not only ‘closed’(kept secret from the research community) as it is consid-ered proprietary, but the formula itself may vary over timedepending on changes in nutrient levels in key ingredi-ents. In addition, vitamin and mineral premixes are addedto these diets which supplement the unknown levels ofmicronutrients provided inherently from other ingredi-ents, and in some cases in excess of the estimated require-ment [7]. One the positive side, GB diets are inexpensiveand have been used since the beginning of lab animalresearch. In addition, they are generally considered tomaintain a healthy phenotype in the animal (though it canbe argued ‘compared to what?’).However, the ingredients used in GB diets are also their

Achilles heel. The extent to which these ingredients areprocessed and the locations and conditions of where theyare harvested can be a source of variation in the nutrientsand non-nutrients (such as phytoestrogen levels) theycontain [8–10]. Therefore, GB diets can vary significantlyfrom batch-to-batch, from formulation to formulation andamong different manufacturers. While variation in nutri-ent content alone should make a researcher reconsiderthe use of a GB diet, the presence and inconstancy ofnon-nutrients (which are generally not listed on the nutri-tion label) in these diets further adds to these concerns.Conceivably, this may inadvertently change the researchquestion being asked in the study, leading to more timeand money spent.There is a growing list of non-nutrient entities in GB

diets such as various phytochemicals (e.g. phytoestrogens,lignans) [11], toxic heavy metals (e.g. arsenic, lead) [12],nitrosamines [13, 14], endotoxins [15] and pesticides andpollutants [16–18]. Recently, Mesnage et al. [18] looked at13 different GB diets from 5 continents and found severalenvironmental contaminants including various pesticides,heavy metals, genetically modified grains, polychlorinatedbiphenyls, polychlorinated dibenzo-p-dioxins and dibenzofu-rans. Their levels in some cases greatly exceeded acceptable

daily intakes and are highly variable among these diets. As itis apparent that these contaminants are not well controlled,it’s conceivable that they could by themselves or in combin-ation alter the toxicological and metabolic phenotype ofrodents. For example, it was found that feeding a GB dietsignificantly induced expression of aryl hydrocarbon recep-tors (AhRs) in intestinal cells – cells that modulate immunityand detoxification [19]. In contrast, expression was not in-duced by feeding a purified ingredient diet. However, theaddition of a known AhR ligand (indole-3 carbinol) to apurified diet recapitulated the effect of the GB diet. Whileindole-3 carbinol is not present in GB diets, it is likely thatother phytochemicals (i.e. phytoestrogens from soybean mealand alfalfa meal) or perhaps environmental contaminantssuch as polychlorinated dibenzo-p-dioxins may serve as AhRligands [20].In contrast to GB diets, purified ingredient diets (also

called purified diets, semi-purified diets) use highly refinedingredients (casein, corn starch, sucrose, cellulose, soy-bean oil, etc.) each of which essentially contains one mainnutrient and little to no non-nutrient chemicals. As aresult, these diets are well-defined and have minimalbatch-to-batch variability [21]. Indeed, it was through theuse of purified ingredient diets that nutrient requirementsfor lab animals were first delineated. Furthermore, the for-mulas are ‘open’ and not kept secret from the scientificcommunity. No diet is without flaws and a good exampleof a needed ‘improvement’ in purified diets is the inclusionof a source(s) of soluble fiber for gut health. Having saidthis, among nutritionally trained scientists, purified dietsare considered a ‘cleaner’, more controlled diet choicecompared to GB diets [4, 7, 21]. Knowing the inherentdifferences between GB diets and purified diets allows theresearcher to design their diet study well and judge papersin which animals fed purified diets were compared directlyto those fed GB diets.Given the inherent differences between GB and purified

diets, it is clear that data produced from these diets shouldnot be compared to each other. Yet, the incidence of im-properly controlled diet studies in the lab animal literature

Table 1 Typical sources of nutrients and non-nutrients in rodent purified ingredient diets and grain-based dietsNutrients orNon-nutrients

Purified Ingredient Diet Grain-Based Diet

Typical Sources Typical Sources

Protein Casein Dehulled soybean meal, ground corn and wheat, whey, alfalfa

Fat Soybean oil, corn oil Porcine animal fat, fish meal, meat meal

Carbohydrate Corn starch, maltodextrin, sucrose Dehulled soybean meal, ground corn, ground oats, wheat middlings

Fiber Refined Cellulose (INSOLUBLE Fiber) Ground corn or wheat, dried beet pulp, ground oats, alfalfa, wheat middlings(SOLUBLE and INSOLUBLE Fibers including cellulose, hemicellulose, lignins and pectin)

Micronutrients Vitamin and mineral premixes Most ingredients, extra micronutrients added

Phytoestrogens None present in diet Mainly soybean meal, alfalfa meal

Heavy Metals None present in diet Mainly from grains and meat meals

Pellizzon and Ricci Nutrition & Metabolism (2018) 15:3 Page 2 of 6

Pellizzon MA, Ricci MR.

Nutr Metab (Lond). 2018 Jan 15;15:3. doi: 10.1186/s12986-018-0243-5. eCollection 2018

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Dietary Studies in Animal Models of High-Fat Feeding: Guidelines for Diet-Comparisons and for Reporting Results

(2008)

Pie chart showing the percentage of 35 original research papers evaluated that used appropriate diet comparisons (14%), that compared chow and defined high-fat diets (43%), or that presented insufficient information to evaluate diet comparisons (34%).

Warden CH, Fisler JS.

Cell Metab. 2008 Apr;7(4):277. doi: 10.1016/j.cmet.2008.03.014.

Summary of diet comparisons in papers published in 2007 in five journals and identified by search terms

‘mouse high fat’ in PubMed. Supplemental Information for Editorial Evaluation

Summary of diet comparisons in papers published in 2007 in five journals and identified by search terms ‘mouse high fat’ in PubMed.

NumberJournal

Papers identified

using search

terms

Insufficient

information to

determine diet

Chow compared

to defined diet

Both chow and

defined diets, but

not compared

Defined diet

compared to

defined diet

Cell Metabolism 7 3 3 1

Diabetes 11 (of 36)* 4 2 2 3

Journal of Clinical Investigation 12 3 7 1 1

Nature 2 2

Nature Medicine 3 2 1

*Only the first 11 of 36 total papers in Diabetes identified using the search terms were used in the diet evaluation.

Papers used in evaluation of diet comparison.

From Cell Metabolism [1-7]; From Diabetes [8-18]; From Journal of Clinical Investigation [19-30]; From Nature [31, 32]; From Nature

Medicine [33-35]

[A] Cover Letter

Papers used in evaluation of diet comparison.From Cell Metabolism [1-7]; From Diabetes [8-18]; From Journal of Clinical Investigation [19-30]; From Nature [31, 32]; From Nature Medicine [33-35]

Warden CH, Fisler JS.

Cell Metab. 2008 Apr;7(4):277. doi: 10.1016/j.cmet.2008.03.014.

Table 1

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The common use of improper control diets in diet-induced metabolic disease research

confounds data interpretation: the fiber factor

Michael A. Pellizzonand Matthew R. Ricci

Nutrition & Metabolism (2018) 15:3

Mouse diet studies 2018

is substantial. In 2008, Warden and Fisler [5] identified 35papers using the search terms ‘mouse high fat’ in fivehigh-impact journals. Of these 35 papers, only 14% used aproperly matched control diet against the high-fat purifiedingredient experimental diet. Forty-three percent of pa-pers improperly used a GB diet as the control and 34% ofthe time, there was not enough information in themethods section to even determine what types of dietswere fed. Despite this high-profile commentary, thesenumbers have not changed very much in recent years. Weused the same search terms in the same journals, andidentified 69 publications published in 2016. In 41% of thepapers, data from mice fed a high-fat purified ingredientdiet were improperly compared to those fed a GB diet. Inanother 41% of the papers, there were insufficient descrip-tions of the diets used and so we could not determinewhat the animals were fed. In only 19% of the papers wasa properly matched, low-fat purified ingredient diet usedin comparison to the purified ingredient high-fat diet(Fig. 1). Thus, it is possible that researchers are attributingphenotypic differences between animals fed a low fat GBdiet and a high fat purified diet to differences in dietaryfat, when in fact they could be due to any number of otherdietary differences.Interestingly, the authors of a recent publication [22]

compared feeding a low-fat GB diet, a high-fat purified

diet and a matched low-fat purified diet to C57Bl/6J mice.As they found no differences in body weight, glucose tol-erance, adipokines or anxiety-like behavior between theGB or low-fat purified diet, they concluded that “chow(GB diet) may be used as an appropriate control diet instudies investigating the effects of chronic high-fat diet in-take on phenotypic, metabolic and behavioral alterations”.In our opinion, this is an overreaching and misleadingstatement to make, given that their study, like any other,was limited in the scope of the endpoints measured. Intheir study, they did find differences in plasma lipids levelsbetween the GB and low-fat purified diets, something theyacknowledge could be due to differences in dietary fiberbetween these diet types. However, the authors fail to notethat dietary fiber differences may (and based on data fromthe literature, will) affect gut morphology and the micro-biome, an area of intense research. This highlights a rele-vant but overlooked confound that occurs any time a highfat purified diet is compared to a GB diet: the vastly differ-ent fiber types and concentrations between these diet types.There is a growing body of evidence that the relation-

ship between diet and metabolic disease is gut-centric.The link between the gut and weight gain was establishedby Turnbaugh et al. [23] who observed that lean, germ-free mice gained more adiposity after they were gavagedwith cecal microbiota from obese ob/ob mice compared tothose gavaged with microbiota from lean mice. Dramaticshifts in certain bacterial phyla can occur within a dayafter switching from a ‘lower fat, plant polysaccharidebased diet’ (an undefined GB diet) to a high fat purifiedingredient diet, and this stabilizes after only 7 days [24].These intriguing findings suggest a rapid and powerfuleffect of diet on changing microbiota which precedes thedevelopment of metabolic disease. While these studieswere significant contributions to our understanding of therole of gut microbiota on metabolic disease, the fact thatthe descriptions of the diets were limited reduces ourunderstanding of which particular dietary factor(s) wereimportant to the observations.

Fiber: An X factor in GB diets that has beenignoredOf the many differences between GB and purified ingredi-ent diets, it is arguably the level and type of dietary fiberwhich is most important with respect to the gut micro-biome. Fiber can be generally classified as either solubleor insoluble, and there are different types of each. Bacter-ial fermentation of soluble fiber releases short chain fattyacids (SCFAs), which are a major supplier of energy tocolonocytes and are thought to provide other benefitsincluding prevention of diet-induced obesity, decreasedadipose tissue storage, and improved insulin action [25].An increase in SCFAs can change the gut pH, which inturn can decrease the populations of pathogenic, pH-

Fig. 1 Diet comparisons in recent research publications. Pie chartshowing the percentages of 69 publications evaluated (using searchterms ‘mouse high fat’) that used appropriate diet comparisons (19%), thatcompared GB diets and purified high-fat diets (41%), and that presentedinsufficient information to evaluate the types of diets used (41%). Thejournals examined were Cell Metabolism (7 papers), Cell (1 paper), Science(1 paper), Journal of Clinical Investigation (15 papers), Nature (3 papers),Nature Medicine (4 papers), and Diabetes (the first 38 of 188 papers)

Pellizzon and Ricci Nutrition & Metabolism (2018) 15:3 Page 3 of 6

Diet comparisons in recent

research publications. Pie chart

showing the percentages of 69

publications evaluated (using

search terms ‘mouse high fat’)

that used appropriate diet

comparisons (19%), that

compared GB diets and purified

high-fat diets (41%), and that

presented insufficient

information to evaluate the

types of diets used (41%). Pellizzon MA, Ricci MR.

Nutr Metab (Lond). 2018 Jan 15;15:3. doi:

10.1186/s12986-018-0243-5. eCollection 2018

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is substantial. In 2008, Warden and Fisler [5] identified 35papers using the search terms ‘mouse high fat’ in fivehigh-impact journals. Of these 35 papers, only 14% used aproperly matched control diet against the high-fat purifiedingredient experimental diet. Forty-three percent of pa-pers improperly used a GB diet as the control and 34% ofthe time, there was not enough information in themethods section to even determine what types of dietswere fed. Despite this high-profile commentary, thesenumbers have not changed very much in recent years. Weused the same search terms in the same journals, andidentified 69 publications published in 2016. In 41% of thepapers, data from mice fed a high-fat purified ingredientdiet were improperly compared to those fed a GB diet. Inanother 41% of the papers, there were insufficient descrip-tions of the diets used and so we could not determinewhat the animals were fed. In only 19% of the papers wasa properly matched, low-fat purified ingredient diet usedin comparison to the purified ingredient high-fat diet(Fig. 1). Thus, it is possible that researchers are attributingphenotypic differences between animals fed a low fat GBdiet and a high fat purified diet to differences in dietaryfat, when in fact they could be due to any number of otherdietary differences.Interestingly, the authors of a recent publication [22]

compared feeding a low-fat GB diet, a high-fat purified

diet and a matched low-fat purified diet to C57Bl/6J mice.As they found no differences in body weight, glucose tol-erance, adipokines or anxiety-like behavior between theGB or low-fat purified diet, they concluded that “chow(GB diet) may be used as an appropriate control diet instudies investigating the effects of chronic high-fat diet in-take on phenotypic, metabolic and behavioral alterations”.In our opinion, this is an overreaching and misleadingstatement to make, given that their study, like any other,was limited in the scope of the endpoints measured. Intheir study, they did find differences in plasma lipids levelsbetween the GB and low-fat purified diets, something theyacknowledge could be due to differences in dietary fiberbetween these diet types. However, the authors fail to notethat dietary fiber differences may (and based on data fromthe literature, will) affect gut morphology and the micro-biome, an area of intense research. This highlights a rele-vant but overlooked confound that occurs any time a highfat purified diet is compared to a GB diet: the vastly differ-ent fiber types and concentrations between these diet types.There is a growing body of evidence that the relation-

ship between diet and metabolic disease is gut-centric.The link between the gut and weight gain was establishedby Turnbaugh et al. [23] who observed that lean, germ-free mice gained more adiposity after they were gavagedwith cecal microbiota from obese ob/ob mice compared tothose gavaged with microbiota from lean mice. Dramaticshifts in certain bacterial phyla can occur within a dayafter switching from a ‘lower fat, plant polysaccharidebased diet’ (an undefined GB diet) to a high fat purifiedingredient diet, and this stabilizes after only 7 days [24].These intriguing findings suggest a rapid and powerfuleffect of diet on changing microbiota which precedes thedevelopment of metabolic disease. While these studieswere significant contributions to our understanding of therole of gut microbiota on metabolic disease, the fact thatthe descriptions of the diets were limited reduces ourunderstanding of which particular dietary factor(s) wereimportant to the observations.

Fiber: An X factor in GB diets that has beenignoredOf the many differences between GB and purified ingredi-ent diets, it is arguably the level and type of dietary fiberwhich is most important with respect to the gut micro-biome. Fiber can be generally classified as either solubleor insoluble, and there are different types of each. Bacter-ial fermentation of soluble fiber releases short chain fattyacids (SCFAs), which are a major supplier of energy tocolonocytes and are thought to provide other benefitsincluding prevention of diet-induced obesity, decreasedadipose tissue storage, and improved insulin action [25].An increase in SCFAs can change the gut pH, which inturn can decrease the populations of pathogenic, pH-

Fig. 1 Diet comparisons in recent research publications. Pie chartshowing the percentages of 69 publications evaluated (using searchterms ‘mouse high fat’) that used appropriate diet comparisons (19%), thatcompared GB diets and purified high-fat diets (41%), and that presentedinsufficient information to evaluate the types of diets used (41%). Thejournals examined were Cell Metabolism (7 papers), Cell (1 paper), Science(1 paper), Journal of Clinical Investigation (15 papers), Nature (3 papers),Nature Medicine (4 papers), and Diabetes (the first 38 of 188 papers)

Pellizzon and Ricci Nutrition & Metabolism (2018) 15:3 Page 3 of 6

2008 2018Little to no change in quality of mouse diet studies 2008 to 2018

Pellizzon MA, Ricci MR.

Nutr Metab (Lond). 2018 Jan 15;15:3. doi: 10.1186/s12986-018-0243-5. eCollection 2018

Warden CH, Fisler JS.

Cell Metab. 2008 Apr;7(4):277. doi: 10.1016/j.cmet.2008.03.014.Cited 90 times as of June 6, 2018

(1) Blocking Single Gene Prevents Obesity in Fat-Fed Mice

• “We gave the mice a diet that more or less corresponds to continuously eating burgers and pizza,” comments Karen Nørgaard Nielsen, who is a Ph.D. student at the Novo Nordisk Foundation Center for Basic Metabolic Research, and first author on the team’s published paper in Molecular Metabolism.

• “Still, it was impossible for them to expand their fat tissue.”• Mice were genetically engineered to not make the protein “nicotinamide adenine

dinucleotide (NAD+) biosynthetic enzyme Nicotinamide phosphoribosyltransferase(NAMPT). NAMPT acts intracellularly to catalyze the rate-limiting step of the NADþsalvage pathway, the main source of adipose NAD+.

• NAMPT-mediated NAD+ biosynthesis is indispensable for adipose tissue plasticity and development of obesity.

• The source paper is: – Nielsen KN, Peics J, Ma T, Karavaeva I, Dall M, Chubanava S, Basse AL, Dmytriyeva O, Treebak

JT, Gerhart-Hines Z. Mol Metab. 2018 May;11:178-188. doi: 10.1016/j.molmet.2018.02.014. Epub 2018 Mar 7

• The quotes are from: – Daily update ⋅ May 4, 2018– Genetic Engineering & Biotechnology News

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What was actually done…• The chow control diet was Altromin diet number 1310

which was compared to a purified diet from Research Diets.

• The 1310 formula is a grain-based (soy, wheat, corn) fixed formula which is free of alfalfa and fish/animal meal and deficient in nitrosamines.

• There is a variant of this diet deficient in phytoestrogens – in other words phytoestrogens are in the regular diet!

• The D12492 purified diet used was from Research Diets. It contains casein, maltodextrose, sucrose, lard, fiber from cellulose and some soybean oil.

• So the high fat diet is could be described as a pork fat based ice cream diet, rather than the press release description of burgers and pizza.

Alternate explanation

• The two diets used have no ingredients in common – see Table 1.

• Therefor the only accurate conclusion is that diet did something.

• Although the chow diet contains Arsenic and other metals, the authors choose to describe it as the healthy low fat diet alternative.

• Likely relevance to choosing a healthy human diet?

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(2) What the press release said about HFD and taste buds

• As mice plumped up on a high-fat diet, some of their taste buds vanished. This disappearing act could explain why some people with obesity seem to have a weakened sense of taste, which may compel them to eat more.

• Compared with siblings that were fed normal mouse chow, mice given high-fat meals lost about 25 percent of their taste buds over eight weeks. Buds went missing because mature taste bud cells died off more quickly, and fewer new cells developed to take their place. Chronic, low-level inflammation associated with obesity appears to be behind the loss, researchers report March 20 in PLOS Biology.

• Concluding paragraph “Along with learning more about how taste buds are damaged by inflammation, Dando is interested in working toward new treatments for obesity, perhaps by countering the dulled sense of taste. “These mice lose taste buds,” he says. “Can we bring them back?””

• This quote is from Science News• “Inflammation linked to the disease caused the loss of taste buds in mice”• BY AIMEE CUNNINGHAM 2:00PM, MARCH 20, 2018

• SOURCE PAPER Citation: Kaufman A, Choo E, Koh A, Dando R (2018) Inflammation arising from obesity reduces taste bud abundance and inhibits renewal. PLoS Biol16(3): e2001959. https://doi.org/10.1371/ journal.pbio.2001959

What Kaufman et al did• We have analyzed the effects of obesity on taste

buds and demonstrate that mice consuming a high-fat diet display a pronounced loss of taste buds when compared to littermates sustained on a healthy diet.

• When the inflammatory response is impeded via genetic manipulation, we observe that mice no longer suffer taste loss, suggesting that taste dysfunction in obesity is a result of systemic inflammation.

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Diets for Kaufman et al• Control diet was Harlan Teklad 8604. • Ingredients (in descending order of inclusion)-

Dehulled soybean meal, wheat middlings, flaked corn, ground corn, fish meal, cane molasses, ground wheat, dried whey, soybean oil, brewers dried yeast.

• Experimental diet was a purified diet Harlan TekladTD.03584. Ingredients:

• Casein 230 g/kg, • Lard 350g/kg, • Sucrose 150g/kg • Maltodextrin 191g/kg• Vitamins minerals methionine. • No mention of cellulose or any other fiber.

Alternate explanation for Kaufman and taste buds

• The authors have compared a fiber rich Grain based chow to a purified defined high-fat high-sucrose diet.

• The two diets have no ingredients in common.• Take your pick of causal ingredients.• Finally, the authors assume that obesity causes a

change of inflammation which causes a decrease of taste buds, but it is also possible that different ingredients of the two diets have direct influences on taste buds or inflammation.

• For example, lots of data says that fiber reduces inflammation…!

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(3) An aberrant lipogenic program promotes metastatic prostate cancer Chen et al

• What the authors said:• Lipids, either endogenously synthesized or exogenous,

have been linked to human cancer. • A high-fat diet (HFD) induced lipid accumulation in

prostate tumors and was sufficient to drive metastasis in a nonmetastatic mouse model of Prostate Cancer.

• Thus, our findings uncover a prometastatic lipogenicprogram and lend direct genetic and experimental support to the notion that a Western HFD can promote metastasis.

• Nature Genetics | VOL 50 | FEBRUARY 2018 | 206–218

What the New York Times said about the Mouse

Prostate Cancer study• Obesity is linked to prostate cancer, scientists know, but it’s not clear why.

On Monday, researchers reported a surprising connection.

• When prostate cancers lose a particular gene, they become tiny fat factories, a team at Beth Israel Deaconess Medical Center in Boston reported in a paper published in Nature Genetics.

• Then the cancers spread from the prostate, often with deadly effect. Prostate cancers that have not lost that gene also can spread, or metastasize — in mice, at least — but only if they have a ready source of fat from the diet.

• That finding suggests that dietary fat can substitute for the loss of the gene, fueling prostate cancer. Moreover, the investigators found, an obesity drug that blocks fat production can make metastatic prostate cancers regress in mice and prevent them from spreading. ……..More

• They also wonder if low-fat diets might help these patients, and what kinds of dietary fat might fuel prostate cancers. https://www.nytimes.com/2018/01/16/health/fat-diet-prostate-cancer.html

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What they actually did

• They chose a lard-based HFD enriched in saturated and monounsaturated FAs and capable of inducing classic HFD effects in rodents (reference 61)

• Here is what reference 61 says…• Diets were prepared in pellet form by Altromin

(Lage, Germany).• Rats had free access to either a standard rodent

chow (SC, fat content 11% of energy), or a high-fat diet (fat content 42% of energy), based on lard (HF-L).

• NO OTHER INFORMATION WAS PROVIDED.

Alternate explanation• Diet ingredients are not provided in the paper nor

on the web site for the manufacturer. This is common practice for non-US producers.

• Although diet does something, no conclusions can be made about the role of any one ingredient.

• The only thing we know for sure is that the high fat diet contains lard, presumably from Germany. Lard fatty acid composition depends on the food sources for pigs.

• The HFD likely contains less fiber because of less carbohydrates.

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Overall conclusions• Mice are an excellent model of genetic

human obesity. • Most genes that cause obesity in humans

cause obesity in mice and vice versa. • Mice may be a good model of diet induced

obesity, but most experiments are not designed to determine effects of one or two ingredients.

• Most mouse diet studies can only conclude: • “Diet does something to health”.