Abstract

Circulating microRNAs (miRNAs) have been implicated in controlling whole-body metabolism through intercellular communications. MicroRNA-193b (miR-193b) plays essential roles in white and brown adipocyte adipogenesis and regulating adipokine secretion. We tested whether changes in circulating miR-193b were associated with reductions of adiposity and various fat depots in response to weight-loss dietary and lifestyle interventions in two independent trials. This study included participants of a 2-year weight-loss diet intervention trial (POUNDS Lost) with data on changes in circulating miR-193b-5p from baseline to 6 months after interventions (n=509) . We also assessed changes in circulating miR-193b-5p over 18 months in the CENTRAL weight-loss lifestyle intervention trial (n=111) . At baseline, higher miR-193b was associated with greater adiposity, energy expenditure, ectopic fat depots, and lower adiponectin levels. In response to the interventions, decreases in miR-193b were associated with larger reductions of weight (p <.0001) , waist circumference (p <.0001) , and whole-body total % fat mass (p=0.03) at 6 months in the POUNDS Lost trial. In the CENTRAL trial, decreases in miR-193b were associated with larger reductions of weight (p=0.03) , total (p=0.002) and visceral adipose tissue (p=0.004) , and different fat depots (deep and superficial subcutaneous, and hepatic fat; p <0.for all) . In both trials, every 1 SD decrease of miR-193b was associated with an increased probability for the achievement of successful weight loss (-5% or more weight loss) at the end of interventions (odds ratio [OR]: 1.4; p=0.0in POUNDS Lost; OR 1.9; p=0.02 in CENTRAL) . In conclusion, changes in circulating miR-193b in response to weight-loss diet/lifestyle interventions were significantly associated with the long-term successful weight loss and reductions of fat depots closely related to the risk of diabetes. Disclosure Y.Heianza: None. F.Sacks: None. L.Qi: None. Q.Xue: None. J.Rood: None. K.K.Krohn: None. A.Yaskolka meir: None. M.Blüher: Consultant; AstraZeneca, Lilly, Novo Nordisk A/S, Pfizer Inc., Sanofi, Speaker's Bureau; Bayer AG, Boehringer Ingelheim International GmbH, Novartis AG. P.Kovacs: None. I.Shai: None. G.Bray: None. Funding NIH (DK091718, DK100383, DK115679)

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