RT Journal Article SR Electronic T1 Manipulation of Dietary Amino Acids Prevents and Reverses Obesity in Mice Through Multiple Mechanisms That Modulate Energy Homeostasis JF Diabetes JO Diabetes FD American Diabetes Association SP 2324 OP 2339 DO 10.2337/db20-0489 VO 69 IS 11 A1 Ruocco, Chiara A1 Ragni, Maurizio A1 Rossi, Fabio A1 Carullo, Pierluigi A1 Ghini, Veronica A1 Piscitelli, Fabiana A1 Cutignano, Adele A1 Manzo, Emiliano A1 Ioris, Rafael Maciel A1 Bontems, Franck A1 Tedesco, Laura A1 Greco, Carolina M. A1 Pino, Annachiara A1 Severi, Ilenia A1 Liu, Dianxin A1 Ceddia, Ryan P. A1 Ponzoni, Luisa A1 Tenori, Leonardo A1 Rizzetto, Lisa A1 Scholz, Matthias A1 Tuohy, Kieran A1 Bifari, Francesco A1 Di Marzo, Vincenzo A1 Luchinat, Claudio A1 Carruba, Michele O. A1 Cinti, Saverio A1 Decimo, Ilaria A1 Condorelli, Gianluigi A1 Coppari, Roberto A1 Collins, Sheila A1 Valerio, Alessandra A1 Nisoli, Enzo YR 2020 UL http://diabetes.diabetesjournals.org/content/69/11/2324.abstract AB Reduced activation of energy metabolism increases adiposity in humans and other mammals. Thus, exploring dietary and molecular mechanisms able to improve energy metabolism is of paramount medical importance because such mechanisms can be leveraged as a therapy for obesity and related disorders. Here, we show that a designer protein-deprived diet enriched in free essential amino acids can 1) promote the brown fat thermogenic program and fatty acid oxidation, 2) stimulate uncoupling protein 1 (UCP1)-independent respiration in subcutaneous white fat, 3) change the gut microbiota composition, and 4) prevent and reverse obesity and dysregulated glucose homeostasis in multiple mouse models, prolonging the healthy life span. These effects are independent of unbalanced amino acid ratio, energy consumption, and intestinal calorie absorption. A brown fat-specific activation of the mechanistic target of rapamycin complex 1 seems involved in the diet-induced beneficial effects, as also strengthened by in vitro experiments. Hence, our results suggest that brown and white fat may be targets of specific amino acids to control UCP1-dependent and -independent thermogenesis, thereby contributing to the improvement of metabolic health.