Modeling the Effect of High Calorie Diet on the Interplay between Adipose Tissue, Inflammation, and Diabetes

Abstract

Background. Type 2 diabetes (T2D) is a chronic metabolic disease potentially leading to serious widespread tissue damage. Human organism develops T2D when the glucose-insulin control is broken for reasons that are not fully understood but have been demonstrated to be linked to the emergence of a chronic inflammation. Indeed such low-level chronic inflammation affects the pancreatic production of insulin and triggers the development of insulin resistance, eventually leading to an impaired control of the blood glucose concentration. On the contrary, it is well-known that obesity and inflammation are strongly correlated. Aim. In this study, we investigate in silico the effect of overfeeding on the adipose tissue and the consequent set up of an inflammatory state. We model the emergence of the inflammation as the result of adipose mass increase which, in turn, is a direct consequence of a prolonged excess of high calorie intake. Results. The model reproduces the fat accumulation due to excessive caloric intake observed in two clinical studies. Moreover, while showing consistent weight gains over long periods of time, it reveals a drift of the macrophage population toward the proinflammatory phenotype, thus confirming its association with fatness.