New insights in the mechanisms of weight-loss maintenance: Summary from a Pennington symposium

Emily W Flanagan¹, Redin Spann¹, Sarah E Berry², Hans-Rudolf Berthoud¹, Stephanie Broyles¹, Gary D Foster^{3

4}, Jonathan Krakoff⁵, Ruth J F Loos^{6

7}, Michael R Lowe⁸, Danielle M Ostendorf^{9

10}, Tiffany M Powell-Wiley^{11

12}, Leanne M Redman¹, Michael Rosenbaum¹³, Philip R Schauer¹, Randy J Seeley¹⁴, Boyd A Swinburn¹⁵, Kevin Hall¹⁶, Eric Ravussin¹

Affiliations

¹ Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.
² Department of Nutritional Sciences, King's College London, London, UK.
³ WW International, New York, New York, USA.
⁴ Center for Weight and Eating Disorders, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁵ Obesity and Diabetes Clinical Research Section, Phoenix Epidemiology & Clinical Research Branch, NIDDK-Phoenix, Phoenix, Arizona, USA.
⁶ Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
⁷ The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁸ Drexel University, Philadelphia, Pennsylvania, USA.
⁹ Department of Medicine, Anschutz Health and Wellness Center, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
¹⁰ Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
¹¹ Social Determinants of Obesity and Cardiovascular Risk Laboratory, Cardiovascular Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
¹² Intramural Research Program, National Institute on Minority Health and Health Disparities, National Institutes of Health, Bethesda, Maryland, USA.
¹³ Division of Molecular Genetics and Irving Center for Clinical and Translational Research, Columbia University Irving Medical Center, New York, New York, USA.
¹⁴ Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
¹⁵ School of Population Health, University of Auckland, Auckland, New Zealand.
¹⁶ National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, USA.

PMID: 37845825
PMCID: PMC10915908
DOI: 10.1002/oby.23905

Review

New insights in the mechanisms of weight-loss maintenance: Summary from a Pennington symposium

Emily W Flanagan et al. Obesity (Silver Spring). 2023 Dec.

. 2023 Dec;31(12):2895-2908.

doi: 10.1002/oby.23905. Epub 2023 Oct 16.

Authors

Affiliations

¹ Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.
² Department of Nutritional Sciences, King's College London, London, UK.
³ WW International, New York, New York, USA.
⁴ Center for Weight and Eating Disorders, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁵ Obesity and Diabetes Clinical Research Section, Phoenix Epidemiology & Clinical Research Branch, NIDDK-Phoenix, Phoenix, Arizona, USA.
⁶ Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
⁷ The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁸ Drexel University, Philadelphia, Pennsylvania, USA.
⁹ Department of Medicine, Anschutz Health and Wellness Center, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
¹⁰ Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
¹¹ Social Determinants of Obesity and Cardiovascular Risk Laboratory, Cardiovascular Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
¹² Intramural Research Program, National Institute on Minority Health and Health Disparities, National Institutes of Health, Bethesda, Maryland, USA.
¹³ Division of Molecular Genetics and Irving Center for Clinical and Translational Research, Columbia University Irving Medical Center, New York, New York, USA.
¹⁴ Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
¹⁵ School of Population Health, University of Auckland, Auckland, New Zealand.
¹⁶ National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, USA.

PMID: 37845825
PMCID: PMC10915908
DOI: 10.1002/oby.23905

Abstract

Obesity is a chronic disease that affects more than 650 million adults worldwide. Obesity not only is a significant health concern on its own, but predisposes to cardiometabolic comorbidities, including coronary heart disease, dyslipidemia, hypertension, type 2 diabetes, and some cancers. Lifestyle interventions effectively promote weight loss of 5% to 10%, and pharmacological and surgical interventions even more, with some novel approved drugs inducing up to an average of 25% weight loss. Yet, maintaining weight loss over the long-term remains extremely challenging, and subsequent weight gain is typical. The mechanisms underlying weight regain remain to be fully elucidated. The purpose of this Pennington Biomedical Scientific Symposium was to review and highlight the complex interplay between the physiological, behavioral, and environmental systems controlling energy intake and expenditure. Each of these contributions were further discussed in the context of weight-loss maintenance, and systems-level viewpoints were highlighted to interpret gaps in current approaches. The invited speakers built upon the science of obesity and weight loss to collectively propose future research directions that will aid in revealing the complicated mechanisms involved in the weight-reduced state.

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Conflict of interest statement

CONFLICT OF INTEREST STATEMENT

Gary D. Foster is an employee and shareholder WW International. Sarah E. Berry reports consultancy and options for ZOE Ltd. The other authors declared no conflict of interest.

Figures

**FIGURE 1**
The proposed interplay between environment, physiology, and behaviors on weight-loss maintenance.

**FIGURE 2**
Central mechanisms influencing weight-loss maintenance. Hedonic and homeostatic mechanisms in the brain work together to regulate energy balance and generate eating behavior. In the obesogenic environment, these mechanisms are altered, leading to increased body weight and working against weight-loss management treatments. CCK, cholecystokinin; FFA, free fatty acids; GIP, gastric inhibitory protein; GLP-1, glucagon-like peptide-1. Created with BioRender.com.

**FIGURE 3**
Environmental factors contributing to energy intake. An example of system-level thinking for weight-loss maintenance. Lower (person-level) changes are increasingly difficult in the presence of higher-level systems (e.g., political policies). System-level changes from top-down are hypothesized to produce largest effects.

**FIGURE 4**
The futile cycle of weight loss and weight-loss maintenance. TG, triglycerides.

See this image and copyright information in PMC

References

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New insights in the mechanisms of weight-loss maintenance: Summary from a Pennington symposium

Affiliations

New insights in the mechanisms of weight-loss maintenance: Summary from a Pennington symposium

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical