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Review
. 2021 Jan 28;42(1):1-28.
doi: 10.1210/endrev/bnaa027.

Tissue-Specific Effects of Leptin on Glucose and Lipid Metabolism

Sandra Pereira  1 , Daemon L Cline  1 , Maria M Glavas  1 , Scott D Covey  2 , Timothy J Kieffer  1   3   4
Affiliations
Review

Tissue-Specific Effects of Leptin on Glucose and Lipid Metabolism

Sandra Pereira et al. Endocr Rev. .

Abstract

The discovery of leptin was intrinsically associated with its ability to regulate body weight. However, the effects of leptin are more far-reaching and include profound glucose-lowering and anti-lipogenic effects, independent of leptin's regulation of body weight. Regulation of glucose metabolism by leptin is mediated both centrally and via peripheral tissues and is influenced by the activation status of insulin signaling pathways. Ectopic fat accumulation is diminished by both central and peripheral leptin, an effect that is beneficial in obesity-associated disorders. The magnitude of leptin action depends upon the tissue, sex, and context being examined. Peripheral tissues that are of particular relevance include the endocrine pancreas, liver, skeletal muscle, adipose tissues, immune cells, and the cardiovascular system. As a result of its potent metabolic activity, leptin is used to control hyperglycemia in patients with lipodystrophy and is being explored as an adjunct to insulin in patients with type 1 diabetes. To fully understand the role of leptin in physiology and to maximize its therapeutic potential, the mechanisms of leptin action in these tissues needs to be further explored.

Keywords: glucose; leptin; lipid.

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Figures

Graphical Abstract
Graphical Abstract
Figure 1.
Figure 1.
Metabolic effects of direct leptin action in the central nervous system. Abbreviations: AgRP, agouti-related protein; POMC, proopiomelanocortin; SF1, steroidogenic factor-1.
Figure 2.
Figure 2.
Metabolic effects of direct leptin action in adipose tissues, endocrine pancreas, liver, and skeletal muscle. Abbreviations: LepRb, long isoform of the leptin receptor; VLDL, very low density lipoprotein.
Figure 3.
Figure 3.
Metabolic effects of direct leptin action in the cardiovascular and immune systems.
See this image and copyright information in PMC

References

    1. Flier JS. Starvation in the midst of plenty: reflections on the history and biology of insulin and leptin. Endocr Rev. 2019;40(1):1-16. - PMC - PubMed
    1. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994;372(6505):425-432. - PubMed
    1. Harris RB. Direct and indirect effects of leptin on adipocyte metabolism. Biochim Biophys Acta. 2014;1842(3):414-423. - PMC - PubMed
    1. Van Harmelen V, Reynisdottir S, Eriksson P, et al. Leptin secretion from subcutaneous and visceral adipose tissue in women. Diabetes. 1998;47(6):913-917. - PubMed
    1. Trayhurn P, Thomas ME, Duncan JS, Rayner DV. Effects of fasting and refeeding on ob gene expression in white adipose tissue of lean and obese (oblob) mice. FEBS Lett. 1995;368(3):488-490. - PubMed

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