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Adaptive Responses to Weight Loss

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Abstract

The recidivism rate following otherwise successful weight loss is over 75 %. Evolutionary pressures have likely favored the enrichment of human genomes for alleles favoring energy ingestion, storage, and conservation.

The predicted consequences of this allelic selection would be what almost anyone who has lost weight knows: “Weight loss is difficult, but it is even harder to keep it off.” Despite the biological pressure favoring the storage of excess calories as fat throughout most of human evolution, conventional wisdom on this point is that “behavioral” issues related to persistence of “bad habits” that provoked weight gain in the first place account for much or all of the overwhelmingly tendency toward weight regain. There is, however, a substantial body of evidence that there are strong biological forces—reflected in both energy expenditure and ingestive behaviors—that resist the maintenance of a reduced body weight.

Classical animal studies of energy homeostasis following hypothalamic lesions, weight perturbation, selective breeding, and during hibernation—plus more recent demonstrations of interactions between peripheral signals reflecting somatic energy stores with cellular–molecular substrates in the CNS regulating energy balance—all support the contention that body weight is regulated. Obese and non-obese humans maintaining a 10 % or greater reduced weight show a decline in energy expenditure (~300–400 kcal/day) beyond that predicted by body weight and composition changes. This disproportionate decline in energy expenditure is due primarily to increased skeletal muscle chemomechanical efficiency, as well as changes in autonomic function (decreased sympathetic and increased parasympathetic nervous system tone) and neuroendocrine function (decreased circulating concentrations of bioactive thyroid hormones and the adipocyte-derived hormone leptin). This decline in energy expenditure is accompanied by changes in energy intake (decreased satiety) that act coordinately to favor weight regain. These specific changes in energy homeostatic systems after weight loss are mediated by hypothalamic and higher CNS responses many of which involve the adipocyte-derived hormone leptin.

Delineation of this biology has multiple practical implications in the treatment of obesity. Dynamic weight loss (negative energy balance) and static reduced weight maintenance (energy balance) are physiologically distinct and will require different treatments.

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Acknowledgments

A large number of indispensable collaborators have contributed significantly to the work presented in this chapter. These collaborators include Drs. Jules Hirsch, Louis Aronne and Karen Segal, and the nursing and nutritional staffs at Rockefeller University Hospital, and the Irving Center for Clinical and Translational Research at Columbia University Medical Center; Drs. Krista Vandenborne, Marty Eastlack, and Jack Leigh at the University of Pennsylvania Medical Center; and Drs. Daniel Bloomfield, Dympna Gallagher, Rochelle Goldsmith, Steven Heymsfield, Joy Hirsch, Anthony Magnano, Laurel Mayer, Louis Weimer, and Richard Smiley at Columbia University Medical Center. Recombinant human leptin for our studies has been provided by Amgen, Inc. (Thousand Oaks California) and Amylin Pharmaceuticals Inc. (San Diego, CA). These studies were supported in part by NIH Grants # DK30583, DK26687, DK37948, DK64773, DKP30 26687, RR00102, RR00645, RR024156, and UL1 TR00040 and the Russell Berrie Foundation.

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Authors and Affiliations

  1. Pediatrics, Division of Molecular Medicine, Irving Institute for Clinical Research, Columbia University Medical Center, New York, NY, USA

    Michael Rosenbaum M.D.

  2. Division of Molecular Genetics, Naomi Berrie Diabetes Center, 6th Floor, 1150 St. Nicholas Avenue, New York, NY, 10032, USA

    Michael Rosenbaum M.D.

  3. Diabetes Research, Pediatrics and Medicine, Division of Molecular Genetics, Naomi Berrie Diabetes Center, Columbia University College of Physicians and Surgeons, New York, NY, USA

    Rudolph L. Leibel M.D.

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  1. Michael Rosenbaum M.D.
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  2. Rudolph L. Leibel M.D.
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Correspondence to Michael Rosenbaum M.D. .

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Editors and Affiliations

  1. Department of Medicine, Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA

    Robert F. Kushner

  2. Endocrinology, University of Colorado School of Medicine, Denver, Colorado, USA

    Daniel H. Bessesen

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Rosenbaum, M., Leibel, R.L. (2014). Adaptive Responses to Weight Loss. In: Kushner, R., Bessesen, D. (eds) Treatment of the Obese Patient. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1203-2_7

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