Review

Leptin and the maintenance of elevated body weight

  • Nature Reviews Neuroscience volume 19, pages 95105 (2018)
  • doi:10.1038/nrn.2017.168
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Abstract

Obesity represents the single most important risk factor for early disability and death in developed societies, and the incidence of obesity remains at staggering levels. CNS systems that modulate energy intake and expenditure in response to changes in body energy stores serve to maintain constant body adiposity; the adipocyte-derived hormone leptin and its receptor (LEPR) represent crucial regulators of these systems. As in the case of insulin resistance, a variety of mechanisms (including feedback inhibition, inflammation, gliosis and endoplasmic reticulum stress) have been proposed to interfere with leptin action and impede the systems that control body energy homeostasis to promote or maintain obesity, although the relative importance and contribution of each of these remain unclear. However, LEPR signalling may be increased (rather than impaired) in common obesity, suggesting that any obesity-associated defects in leptin action must result from lesions somewhere other than the initial LEPR signal. It is also possible that increased LEPR signalling could mediate some of the obesity-associated changes in hypothalamic function.

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Acknowledgements

The authors were supported by the Michigan Diabetes Research Center (P30 DK020572), the American Diabetes Association, the Marilyn H. Vincent Foundation, the US National Institutes of Health (DK56731 and DK78056) and the Cell and Molecular Biology (CMB) Training Grant (T32GM007315). The authors thank D. Olson, D. Sandoval, R. Seeley and members of the Myers laboratory for helpful discussions.

Author information

Affiliations

  1. Graduate Program in Cellular and Molecular Biology, University of Michigan.

    • Warren W. Pan
    •  & Martin G. Myers Jr
  2. Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan.

    • Warren W. Pan
    •  & Martin G. Myers Jr
  3. Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan 48109, USA.

    • Martin G. Myers Jr

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Contributions

M.G.M. was involved in researching data for the article, made a substantial contribution to discussion of content and wrote, reviewed and edited the manuscript before submission. W.W.P. was involved in researching data for the article, made a substantial contribution to the discussion of content and wrote, reviewed and edited the manuscript before submission.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Martin G. Myers Jr.

Glossary

Energy expenditure

The burning of calories by an organism on normal metabolism (basal metabolic rate) and activity.

Hyperphagia

Literally meaning 'eating too much', it is the consumption of more calories than needed to maintain energy homeostasis and results in the deposition of excess calories in adipose tissue.

Energy homeostasis

The process by which the number of calories eaten are matched to the number of calories burned to maintain a constant body weight; also known as energy balance.

White adipose tissue

The tissue commonly thought of as fat; major depots are found under the skin and inside the abdominal cavity.

Orexigenic

A type of stimuli that increases feeding.

Systemic inflammation

An immune response to infection or other insults that increases the activity of immune cells in the body.

Gut microbiome

The bacteria and other microorganisms that colonize the lumen of the gut.