Nutrition, the visceral immune system, and the evolutionary origins of pathogenic obesity

Abstract

The global obesity epidemic is the subject of an immense, diversely specialized research effort. An evolutionary analysis reveals connections among disparate findings, starting with two well-documented facts: Obesity-associated illnesses (e.g., type-2 diabetes and cardiovascular disease), are especially common in: (i) adults with abdominal obesity, especially enlargement of visceral adipose tissue (VAT), a tissue with important immune functions; and (ii) individuals with poor fetal nutrition whose nutritional input increases later in life. I hypothesize that selection favored the evolution of increased lifelong investment in VAT in individuals likely to suffer lifelong malnutrition because of its importance in fighting intraabdominal infections. Then, when increased nutrition violates the adaptive fetal prediction of lifelong nutritional deficit, preferential VAT investment could contribute to abdominal obesity and chronic inflammatory disease. VAT prioritization may help explain several patterns of nutrition-related disease: the paradoxical increase of chronic disease with increased food availability in recently urbanized and migrant populations; correlations between poor fetal nutrition, improved childhood (catch-up) growth, and adult metabolic syndrome; and survival differences between children with marasmus and kwashiorkor malnutrition. Fats and sugars can aggravate chronic inflammation via effects on intestinal bacteria regulating gut permeability to visceral pathogens. The extremes in a nutrition-sensitive trade-off between visceral (immune-function) vs. subcutaneous (body shape) adiposity may have been favored by selection in highly stratified premedicine societies. Altered adipose allocation in populations with long histories of social stratification and malnutrition may be the result of genetic accommodation of developmental responses to poor maternal/fetal conditions, increasing their vulnerability to inflammatory disease.