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.