PT  - JOURNAL ARTICLE
AU  - Ruocco, Chiara
AU  - Ragni, Maurizio
AU  - Rossi, Fabio
AU  - Carullo, Pierluigi
AU  - Ghini, Veronica
AU  - Piscitelli, Fabiana
AU  - Cutignano, Adele
AU  - Manzo, Emiliano
AU  - Ioris, Rafael Maciel
AU  - Bontems, Franck
AU  - Tedesco, Laura
AU  - Greco, Carolina M.
AU  - Pino, Annachiara
AU  - Severi, Ilenia
AU  - Liu, Dianxin
AU  - Ceddia, Ryan P.
AU  - Ponzoni, Luisa
AU  - Tenori, Leonardo
AU  - Rizzetto, Lisa
AU  - Scholz, Matthias
AU  - Tuohy, Kieran
AU  - Bifari, Francesco
AU  - Di Marzo, Vincenzo
AU  - Luchinat, Claudio
AU  - Carruba, Michele O.
AU  - Cinti, Saverio
AU  - Decimo, Ilaria
AU  - Condorelli, Gianluigi
AU  - Coppari, Roberto
AU  - Collins, Sheila
AU  - Valerio, Alessandra
AU  - Nisoli, Enzo
TI  - Manipulation of Dietary Amino Acids Prevents and Reverses Obesity in Mice Through Multiple Mechanisms That Modulate Energy Homeostasis
AID  - 10.2337/db20-0489
DP  - 2020 Nov 01
TA  - Diabetes
PG  - 2324--2339
VI  - 69
IP  - 11
4099  - http://diabetes.diabetesjournals.org/content/69/11/2324.short
4100  - http://diabetes.diabetesjournals.org/content/69/11/2324.full
SO  - Diabetes2020 Nov 01; 69
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.