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

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 =...

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Published in	Cell metabolism Vol. 23; no. 4; pp. 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	Journal Article
Language	English
Published	United States Elsevier Inc 12.04.2016
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
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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. [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.
AbstractList	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% plus or minus 0.9% (n = 19), 10.8% plus or minus 1.3% (n = 9), and 16.4% plus or minus 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 beta cell function, without a concomitant change in systemic or subcutaneous adipose tissue markers of inflammation. Additional weight loss further improved beta 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. 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.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. 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. 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. 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. Five percent 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. 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.
Author	Magkos, Faidon Kirbach, Kyleigh Kelly, Shannon C. de las Fuentes, Lisa He, Songbing Yoshino, Jun Patterson, Bruce W. Klein, Samuel Fraterrigo, Gemma Luecking, Courtney Okunade, Adewole L.
AuthorAffiliation	1 Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, MO, USA 4 Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China 2 Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (ASTAR); and Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 3 Department of Medicine, Cardiovascular Division, Washington University School of Medicine, St. Louis, MO, USA
AuthorAffiliation_xml	– name: 2 Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (ASTAR); and Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore – name: 1 Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, MO, USA – name: 3 Department of Medicine, Cardiovascular Division, Washington University School of Medicine, St. Louis, MO, USA – name: 4 Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
Author_xml	– sequence: 1 givenname: Faidon surname: Magkos fullname: Magkos, Faidon organization: Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA – sequence: 2 givenname: Gemma surname: Fraterrigo fullname: Fraterrigo, Gemma organization: Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA – sequence: 3 givenname: Jun surname: Yoshino fullname: Yoshino, Jun organization: Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA – sequence: 4 givenname: Courtney surname: Luecking fullname: Luecking, Courtney organization: Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA – sequence: 5 givenname: Kyleigh surname: Kirbach fullname: Kirbach, Kyleigh organization: Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA – sequence: 6 givenname: Shannon C. surname: Kelly fullname: Kelly, Shannon C. organization: Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA – sequence: 7 givenname: Lisa surname: de las Fuentes fullname: de las Fuentes, Lisa organization: Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA – sequence: 8 givenname: Songbing surname: He fullname: He, Songbing organization: Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA – sequence: 9 givenname: Adewole L. surname: Okunade fullname: Okunade, Adewole L. organization: Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA – sequence: 10 givenname: Bruce W. surname: Patterson fullname: Patterson, Bruce W. organization: Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA – sequence: 11 givenname: Samuel surname: Klein fullname: Klein, Samuel email: sklein@dom.wustl.edu organization: Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/26916363$$D View this record in MEDLINE/PubMed
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Snippet	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... 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...
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SubjectTerms	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
Title	Effects of Moderate and Subsequent Progressive Weight Loss on Metabolic Function and Adipose Tissue Biology in Humans with Obesity
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