A Designer Diet Induces Thermogenic Adipocytes via Raptor and Prolongs Healthy Lifespan

Abstract

Reduced activity of thermogenic adipocytes leads to increased adiposity and defects in glucose metabolism. Thus, exploring dietary and molecular mechanisms able to stimulate these adipocytes is of paramount medical importance, as such mechanisms can be leveraged as a therapy for obesity and/or type 2 diabetes. Here, we show that a designer diet enriched in soluble essential amino acids can i) promote brown fat thermogenesis, ii) promote uncoupling protein 1 (UCP1)-independent respiration in subcutaneous white adipose tissue, iii) prevent and reverse obesity and dysregulated glucose metabolism, and iv) prolong healthy lifespan in mice. Mechanistically, our data reveal that this nutritional approach induces mTOR complex 1 (mTORC1), and that the regulatory mTORC1-associated protein Raptor in adipocytes is required for the diet-induced beneficial effects. Hence, we identified a dietary regimen able to induce UCP1-dependent and -independent activation of thermogenic adipocytes, demonstrating a putative therapeutic approach for treating obesity and type 2 diabetes.