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Review ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Genet. | doi: 10.3389/fgene.2019.01015

Physiological and epigenetic features of Yoyo dieting and weight control

  • 1Research Unit Neurobiology of Diabetes, Helmholtz Zentrum München, Germany

Overweight and obesity have become a worldwide epidemic affecting more than 1.9 billion adults and 340 million children. Efforts to curb this global health burden by developing effective long-term non-surgical weight loss interventions continue to fail due to weight regain after weight loss. This weight cycling, often referred to as Yoyo-dieting, is driven by physiological counter-regulatory mechanisms that aim at preserving energy, i.e. decreased energy expenditure, increased energy intake, and impaired brain-periphery communication. Models based on genetically determined set points explained some of the weight control mechanisms, but exact molecular underpinnings remained elusive. Today, gene-environment interactions begin to emerge as likely drivers for the obesogenic memory effect associated with weight cycling. Here, epigenetic mechanisms, including histone modifications, DNA methylation and chromatin remodelling, appear as most likely mechanisms that underpin long-lasting deleterious adaptations or an imprinted obesogenic memory that prevents weight loss maintenance. In this review, we interrogate the role of epigenetic mechanisms for the control and maintenance of body weight. We first summarize human and murine studies on the Yoyo dieting phenomenon and describe physiological adaptations associated with weight loss and weight re-gain. Next, we highlight the specific roles of homeostatic and hedonic food intake control centres in the CNS, and summarize current evidence linking epigenetic mechanisms with CNS reward behavior, obesity and weight cycling. Last, we describe major opportunities and challenges associated with studying epigenetic mechanisms in the CNS with its highly heterogenous cell populations, and provide a summary of recent technological advances that will help to delineate whether an obese memory is based upon epigenetic mechanisms.

Keywords: Weight Loss, yoyo-dieting, CNS, epigenetic mechanims, obesogenic memory

Received: 07 Mar 2019; Accepted: 24 Sep 2019.

Copyright: © 2019 Contreras, Schriever and Pfluger. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Paul T. Pfluger, Research Unit Neurobiology of Diabetes, Helmholtz Zentrum München, Neuherberg, Germany,