title: Effects of Moderate and Subsequent Progressive Weight Loss on Metabolic Function and Adipose Tissue Biology in Humans with Obesity.
abstract: 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.
authors.affiliation: Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A(∗)STAR); and Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore 117597, Singapore, Singapore.
authors.forename: Faidon
authors.initials: F
authors.lastname: Magkos
authors.affiliation: Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Gemma
authors.initials: G
authors.lastname: Fraterrigo
authors.affiliation: Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Yoshino
authors.affiliation: Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Courtney
authors.initials: C
authors.lastname: Luecking
authors.affiliation: Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Kyleigh
authors.initials: K
authors.lastname: Kirbach
authors.affiliation: Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Shannon C
authors.initials: SC
authors.lastname: Kelly
authors.affiliation: Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Cardiovascular Division, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: de las Fuentes
authors.affiliation: Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215021, China.
authors.forename: Songbing
authors.initials: S
authors.lastname: He
authors.affiliation: Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Adewole L
authors.initials: AL
authors.lastname: Okunade
authors.affiliation: Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Bruce W
authors.initials: BW
authors.lastname: Patterson
authors.affiliation: Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: sklein@dom.wustl.edu.
authors.forename: Samuel
authors.initials: S
authors.lastname: Klein
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism / Q000503:physiopathology*; D000328:Adult; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000378:metabolism / Q000503:physiopathology; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology*; D015431:Weight Loss
chemical_list: D007328:Insulin