Dietary carbohydrates modulate metabolic and β-cell adaptation to high-fat diet-induced obesity

Abstract

Obesity is associated with several chronic co-morbidities one of which is type 2 diabetes mellitus (T2DM). The pathogenesis of obesity and T2DM are influenced by alterations in diet macronutrient composition which regulate energy expenditure, metabolic function, glucose homeostasis and pancreatic islet cell biology. Recent studies suggest that increased intake of dietary carbohydrates plays a previously underappreciated role in the promotion of obesity and consequent metabolic dysfunction. Thus, in this study, we utilized mouse models to test the hypothesis that dietary carbohydrates modulate energetic, metabolic and islet adaptions to high fat diets. To address this, we exposed C57BL/6J mice to 12 weeks of 3 eucaloric high fat diets (>60% calories from fat) with varying total carbohydrate (1-20%) and sucrose (0-20%) content. Our results show that severe restriction of dietary carbohydrates characteristic of ketogenic diets reduces body fat accumulation, enhances energy expenditure and reduces prevailing glycemia and insulin resistance compared to carbohydrate-rich high fat diets. Moreover, severe restriction of dietary carbohydrates also results in functional, morphological and molecular changes in pancreatic islets highlighted by restricted capacity for beta cell mass expansion and enhanced functional glucose-responsiveness. These studies support the hypothesis that low carbohydrate/high fat diets provide anti-obesogenic benefits and suggest further evaluation of the effects of these diets on islet biology in humans.