Skip to main page content
U.S. flag
See More

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2013 Jun;7(2):207-22.
doi: 10.1007/s11684-013-0263-5. Epub 2013 Apr 12.

Leptin signaling and leptin resistance

Yingjiang Zhou  1 , Liangyou Rui
Affiliations
Review

Leptin signaling and leptin resistance

Yingjiang Zhou et al. Front Med. 2013 Jun.

Abstract

Leptin is secreted into the bloodstream by adipocytes and is required for the maintenance of energy homeostasis and body weight. Leptin deficiency or genetic defects in the components of the leptin signaling pathways cause obesity. Leptin controls energy balance and body weight mainly through leptin receptor b (LEPRb)-expressing neurons in the brain, particularly in the hypothalamus. These LEPRb-expressing neurons function as the first-order neurons that project to the second-order neurons located within and outside the hypothalamus, forming a neural network that controls the energy homeostasis and body weight. Multiple factors, including inflammation and endoplasmic reticulum (ER) stress, contribute to leptin resistance. Leptin resistance is the key risk factor for obesity. This review is focused on recent advance about leptin action, leptin signaling, and leptin resistance.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1. Leptin signaling pathways
Leptin binds to LEPRb and activates JAK2. JAK2 phosphorylates LEPRb on Tyr985, Tyr1077 and Tyr1138. Phospho-Tyr985, -Tyr1077 and -Tyr1138 bind to downstream molecules and activate the JAK2/STAT3, JAK2/STAT5, PI3K/IRS/AKT, and SHP2/ERK pathways. These pathways act coordinately to regulate energy balance and body weight. LEPRb signaling is regulated both negatively by SOCS3, PTP1B, TCPTP, PTEN and RPTPe and positively by SH2B1. Many factors, including hyperleptinemia, inflammation, ER stress, and defective autophagy, contribute to leptin resistance.
Fig. 2
Fig. 2. Leptin-targetedt neurons and neural circuits
Leptin directly suppresses NPY/AgRP neurons and stimulates POMC/CART neurons in the ARC. ARC neurons project to multiple hypothalamic areas including the DMH, VMH, PVH, and LHA. Leptin also directly activates LEPRb in DMH, VMH, PVH, and LHA neurons. The PVH and LHA are important hypothalamic output pathways that mediate leptin’s anti-obesity action. VTA: ventral tegmental area; NTS: solitary nucleus; IML: intermediolateral cell column.
See this image and copyright information in PMC

References

    1. Kopelman PG. Obesity as a medical problem. Nature. 2000;404(6778):635–643. - PubMed
    1. Finucane MM, Stevens GA, Cowan MJ, Danaei G, Lin JK, Paciorek CJ, Singh GM, Gutierrez HR, Lu Y, Bahalim AN, Farzadfar F, Riley LM, Ezzati M. National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9.1 million participants. Lancet. 2011;377(9765):557–567. - PMC - PubMed
    1. Schwartz MW, Woods SC, Porte D, Jr, Seeley RJ, Baskin DG. Central nervous system control of food intake. Nature. 2000;404(6778):661–671. - 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. Tartaglia LA, Dembski M, Weng X, Deng N, Culpepper J, Devos R, Richards GJ, Campfield LA, Clark FT, Deeds J, Muir C, Sanker S, Moriarty A, Moore KJ, Smutko JS, Mays GG, Wool EA, Monroe CA, Tepper RI. Identification and expression cloning of a leptin receptor, OB-R. Cell. 1995;83(7):1263–1271. - PubMed