Effects of Moderate and Subsequent Progressive Weight Loss on Metabolic Function and Adipose Tissue Biology in Humans with Obesity

• Published in: Cell metabolism 2016-04, Vol.23 (4), p.591-601
• Main Authors: Magkos, Faidon, Fraterrigo, Gemma, Yoshino, Jun, Luecking, Courtney, Kirbach, Kyleigh, Kelly, Shannon C., de las Fuentes, Lisa, He, Songbing, Okunade, Adewole L., Patterson, Bruce W., Klein, Samuel
• Format: Article
• Language: English
• Subjects: Adipose Tissue - metabolism; Adipose Tissue - physiopathology; Adult; Female; Humans; Insulin - metabolism; Insulin Resistance; Insulin-Secreting Cells - metabolism; Insulin-Secreting Cells - pathology; Liver - metabolism; Liver - physiopathology; Male; Middle Aged; Muscles - metabolism; Muscles - physiopathology; Obesity - metabolism; Obesity - physiopathology; Weight Loss
• ISSN: 1550-4131; 1932-7420; 1932-7420
• DOI: 10.1016/j.cmet.2016.02.005

Although 5%–10% weight loss is routinely recommended for people with obesity, the precise effects of 5% and further weight loss on metabolic health are unclear. We conducted a randomized controlled trial that evaluated the effects of 5.1% ± 0.9% (n = 19), 10.8% ± 1.3% (n = 9), and 16.4% ± 2.1% (n = 9) weight loss and weight maintenance (n = 14) on metabolic outcomes. 5% weight loss improved adipose tissue, liver and muscle insulin sensitivity, and β cell function, without a concomitant change in systemic or subcutaneous adipose tissue markers of inflammation. Additional weight loss further improved β cell function and insulin sensitivity in muscle and caused stepwise changes in adipose tissue mass, intrahepatic triglyceride content, and adipose tissue expression of genes involved in cholesterol flux, lipid synthesis, extracellular matrix remodeling, and oxidative stress. These results demonstrate that moderate 5% weight loss improves metabolic function in multiple organs simultaneously, and progressive weight loss causes dose-dependent alterations in key adipose tissue biological pathways. [Display omitted] •Moderate 5% weight loss improves multi-organ insulin sensitivity and β cell function•Additional weight loss of 11%–16% further increases insulin sensitivity in muscle•Progressive weight loss causes stepwise changes in adipose tissue biology Magkos et al. demonstrate the profound therapeutic effects of weight loss on metabolic function in subjects with obesity. Even a moderate 5% weight loss has considerable health benefits, including decreased intra-abdominal and intra-hepatic fat and increased multi-organ insulin sensitivity and β cell function. Additional weight loss further improves many cardiometabolic outcomes.