Multiple Leptin Signalling Pathways in the Control of Metabolism and Fertility: A Means to Different Ends?
Centre for Neuroendocrinology, Department of Anatomy, University of Otago, Dunedin 9016, New Zealand
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Academic Editor: Juan Roa Rivas
Int. J. Mol. Sci. 2021, 22(17), 9210; https://doi.org/10.3390/ijms22179210
Received: 12 July 2021
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Revised: 13 August 2021
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Accepted: 23 August 2021
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Published: 26 August 2021
(This article belongs to the Special Issue Adipokines in Health and Diseases 2.0)
The adipocyte-derived ‘satiety promoting’ hormone, leptin, has been identified as a key central regulator of body weight and fertility, such that its absence leads to obesity and infertility. Plasma leptin levels reflect body adiposity, and therefore act as an ‘adipostat’, whereby low leptin levels reflect a state of low body adiposity (under-nutrition/starvation) and elevated leptin levels reflect a state of high body adiposity (over-nutrition/obesity). While genetic leptin deficiency is rare, obesity-related leptin resistance is becoming increasingly common. In the absence of adequate leptin sensitivity, leptin is unable to exert its ‘anti-obesity’ effects, thereby exacerbating obesity. Furthermore, extreme leptin resistance and consequent low or absent leptin signalling resembles a state of starvation and can thus lead to infertility. However, leptin resistance occurs on a spectrum, and it is possible to be resistant to leptin’s metabolic effects while retaining leptin’s permissive effects on fertility. This may be because leptin exerts its modulatory effects on energy homeostasis and reproductive function through discrete intracellular signalling pathways, and these pathways are differentially affected by the molecules that promote leptin resistance. This review discusses the potential mechanisms that enable leptin to exert differential control over metabolic and reproductive function in the contexts of healthy leptin signalling and of diet-induced leptin resistance.
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Keywords:
leptin; signalling pathways; fertility; metabolism; leptin resistance; STAT3; PI3K; Akt; CRTC
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MDPI and ACS Style
Evans, M.C.; Lord, R.A.; Anderson, G.M. Multiple Leptin Signalling Pathways in the Control of Metabolism and Fertility: A Means to Different Ends? Int. J. Mol. Sci. 2021, 22, 9210. https://doi.org/10.3390/ijms22179210
AMA Style
Evans MC, Lord RA, Anderson GM. Multiple Leptin Signalling Pathways in the Control of Metabolism and Fertility: A Means to Different Ends? International Journal of Molecular Sciences. 2021; 22(17):9210. https://doi.org/10.3390/ijms22179210
Chicago/Turabian StyleEvans, Maggie C., Rebecca A. Lord, and Greg M. Anderson. 2021. "Multiple Leptin Signalling Pathways in the Control of Metabolism and Fertility: A Means to Different Ends?" International Journal of Molecular Sciences 22, no. 17: 9210. https://doi.org/10.3390/ijms22179210
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