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

Faidon Magkos, Gemma Fraterrigo, Jun Yoshino, Courtney Luecking, Kyleigh Kirbach, Shannon C. Kelly, Lisa De Las Fuentes, Songbing He, Adewole L. Okunade, Bruce W. Patterson, Samuel Klein

Research output: Contribution to journalArticlepeer-review

396 Scopus citations


Summary 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.

Original languageEnglish
Pages (from-to)591-601
Number of pages11
JournalCell Metabolism
Issue number4
StatePublished - Apr 12 2016

Bibliographical note

Funding Information:
This study was supported by National Institutes of Health grants DK 37948, DK 104995, DK 56341 (Nutrition Obesity Research Center), DK20579 (Diabetes Research Center), and RR024992 (Clinical and Translational Science Award), a KL2 Career Development Award (TR 000450), and grants from the Pershing Square Foundation and the Longer Life Foundation. The authors thank Freida Custodio and Jennifer Shew for technical assistance, the research coordinators of the Center for Human Nutrition and the staff of the Clinical Research Unit for their help in performing the studies, and the study subjects for their participation.

Publisher Copyright:
© 2016 Elsevier Inc.

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology


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