Cultural and Biological Factors That May Underlie Obesity Disparities. Stephen J D O Keefe University of Pittsburgh

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1 Cultural and Biological Factors That May Underlie Obesity Disparities Stephen J D O Keefe University of Pittsburgh

2 Prevalence Highest in the Micronesian island of Nauru: 85% for males, 93% for females USA: highest in Mississippi: 34% (2009) Associations with gender, ethnicity, and social class May be survival advantages to peripheral fat storage in women Contrast between developing countries where obesity is regarded as a sign of wealth, and developed countries where it is more associated with poverty Change from adolescence to maturity

3 The overall estimated prevalence was 26.7% the greatest prevalences found non-hispanic blacks overall (36.8%), non- Hispanic black women (41.9%), Hispanics (30.7%), and residents of the Midwest (28.2%) and South (28.4%). For both men (22.9%) and women (18.6%), obesity prevalence was smallest among those with a college education; overall, prevalence was greatest among those who did not graduate from high school (32.9%), with prevalences of 29.6% among men and 36.4% among women. CDC 2009 n=405,102

4 State-specific Prevalence of Obesity* Among U.S. Adults, by Race/Ethnicity, White non-hispanic Black non- Hispanic Hispani c (*BMI 30)

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7 The Critical Importance of Culture Epidemiological studies show that the incidence of obesity varies more with population culture than genetic origin Changes from hunter-gatherers to farming communities Changes with westernization Changes within socioeconomic groups

8 Culture The learned patterns of behavior and thought characteristics of a social group Often beyond an individual s control Includes diet, physical activity, religion Influenced by social pressures such as ideals of beauty Shapes individuals beliefs and goals, but constrains choice

9 Problems in the Western World Fat foods exploited by industry for profit Childhood experiences Highly mechanized, dependent on petroleum Food technology geared to profit and palatability: e.g. potato chips, ice cream time squeeze fast foods, large portions, decrease in communal eating at home Cars: drive to the gym! Television: US children spend more time watching TV than any other activity, save sleep

10 TV Promotes inactivity Most ads are related to fast foods Social isolation Reduced community activities, sports participation

11 The Fat and the Thin Fatness is a sign of health and prosperity: e.g. Africa, Italy Thinness a symptom of starvation A fat woman is one well looked after who will look after children well, and has more room for child bearing and lactation and for giving warmth

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13 65% of female hospital workers were obese and 82% males fat depleted

14 Genetic Inheritance The obesogenic environment has different effects on different individuals in the same environment, highlighting an underlying, inherited susceptibility to obesity and fat distribution. Twin studies estimate heritability of body mass index (BMI) to be 40 70% in children and adults Admixture mapping studies demonstrate that obesity correlates closely with the percentage of ancestry derived from ethnic groups with elevated prevalence Common variants with high penetrance do not contribute substantially to risk of common forms of obesity

15 Speliotes EK, Willer CJ, Berndt SI, et al. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat Genet 2010;42(November (11)): Interestingly, some of these loci showed strong sex-specific effects in women

16 Epigenetics Many studies focus on the hypothesis that early environmental influences induce epigenetic variation, thereby permanently affecting metabolism and chronic disease risk. For obesity, it has been shown that obese mothers tend to have obese children Evidence indicates that the establishment of the epigenome can be affected by environmental factors during critical developmental periods the FTO locus is a DNA-demethylase enzyme the MC4R gene which has reduced methylation following long-term exposure to a high fat diet the PPAR protein which interacts with histone acetyltransferases during adipogenesis effect of diet on methylation of POMC and Leptin Herrera et al. Maturitas 2011

17 The Microbiome Black box : difficult to culture, identify and characterize anaerobic bacteria The Genomic era: major breakthrough with cultureindependent identification by high throughput gene sequencing and PCR of conserved regions of 16S rrna Outnumber host cells 10:1, DNA 100:1 800 species (increasing!), 7000 strains, number 100 trillion, weight 1-2Kg A vibrant mass of foreign DNA

18 Abundance of GI Tract Microbes <1% 40-60% 1-5% 10-15% <1% 10-20% <1%

19 The Microbiome Functions Self-survival: dependent on maldigested food Symbiotic: produce SCFAs, folate, biotin, vitamin K, thiamine, riboflavin, B12 Affect energy balance, survival in intestinal failure, obesity risk Educate the GALT Contrabiosis: H 2 S, H 2, 2y bile salt production, Strep bovis, H pylori Activate inflammation in IBD, colon cancer

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21 How Can the Microbiome Influence Obesity Risk? increasing dietary energy harvest promoting fat deposition triggering systemic inflammation modifying locomotor activity central effects on satiety But remember diet is the most important determinant of the microbiota and obesity

22 Bacteria influence Energy Balance and therefore Obesity Germ-free mice had 42% less total body fat than their normal counterparts, even though they consumed 29% more food Transplantation of cecal microbiota from normal mice into the germ-free mice resulted in a 57% increase in total body fat and insulin resistance without increase in food consumption or energy expenditure. Copyright 2004, The National Academy of Sciences The gut microbiota as an environmental factor that regulates fat storage Bäckhed F. et.al. PNAS 2004;101:

23 An obesity-associated gut microbiome with increased capacity for energy harvest Peter J. Turnbaugh, Ruth E. Ley, Michael A. Mahowald, Vincent Magrini, Elaine R. Mardis & Jeffrey I. Gordon Nature 444, (21 December 2006) obesity is associated with changes in the relative abundance of the two dominant bacterial divisions, the Bacteroidetes and the Firmicutes. Bacteroidetes and the Firmicutes are chiefly responsible for salvage of undigested carbohydrate Studies confirmed in mice and men

24 Bacterial Composition Influences SCFA production GF germ free, Bt Bacteroides thetaiotaomicron, MS Methanobrevibacter smithii, Dp Desulfovibrio piger Illustrating that Ms increases energy salvage Samuel B. S., Gordon J. I. PNAS 2006;103: Methanogenesis increases then ability to produce SCFA by removing toxic hydrogen

25 Human Studies 12 obese subjects followed for 1 year following dietary modification to a fatrestricted (FAT-R) or carbohydrate-restricted (CARB-R) low-calorie diet. Baseline: obese individuals had fewer Bacteroidetes and more Firmicutes compared with lean controls End: Bacteroidetes increased, Firmicutes decreased in assocn with weight loss rather than caloric intake changes Ley et al. Nature 2006 Stool samples collected from children aged 6 and 12 months. The children were then followed until aged 7 The children who were overweight or obese at age 7 (n = 25) had fewer Bifidobacteria (P = 0.02) and more Staphylococcus aureus (P = 0.013) at 6 and 12 months of age than children who were normal weight (n = 24). This implies that differences in the composition of gut microbiota may precede the development of obesity. Kalliomaki et al. Am J Clin Nutr 2008

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28 ELSA study: 16S based taxonomic pyrosequencing 3,000 to 20,000 sequences per stool samples 100% NA Succinovibrio AA 90% 80% Ruminococcus Phascolarcto bacterium Roseburia 70% 60% 50% 40% 30% Prevotella Bacteroides 20% 10% Dialister Alistipes Nr seq 0% NA1 NA2 NA3 NA4 NA5 NA6 NA7 NA8 NA9 NA10 NA11 NA12 AA1 AA6 AA8 AA >1000 > > >1000 >1000 > Succinovibrio (generally found in herbivorous rumen) Xylanibacter Streptococcus Collinsella Alistipes. Clear microbiome differences between the two groups, AA more diverse Potential effect of the diet, genera more adapted to resistant starch and rapid fermentation?

29 Tilg and Kaser, JCI 2011

30 Conclusion Obesity disparities are related to a combination of Cultural Genetic Microbiota differences