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Cited by 247

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Leptin Deficiency and Diet-Induced Obesity Reduce Hypothalamic Kisspeptin Expression in Mice

Quennell, Janette H., Howell, Christopher S., Roa, Juan, Augustine, Rachael A., Grattan, David R., Anderson, Greg M.·2011·Endocrinology
DOI 10.1210/en.2010-1100
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Abstract

The hormone leptin modulates a diverse range of biological functions, including energy homeostasis and reproduction. Leptin promotes GnRH function via an indirect action on forebrain neurons. We tested whether leptin deficiency or leptin resistance due to a high-fat diet (HFD) can regulate the potent reproductive neuropeptide kisspeptin. In mice with normalized levels of estradiol, leptin deficiency markedly reduced kisspeptin gene expression, particularly in the arcuate nucleus (ARC), and kisspeptin immunoreactive cell numbers in the rostral periventricular region of the third ventricle (RP3V). The HFD model was used to determine the effects of diet-induced obesity and central leptin resistance on kisspeptin cell number and gene expression. DBA/2J mice, which are prone to HFD-induced infertility, showed a marked decrease in kisspeptin expression in both the RP3V and ARC and cell numbers in the RP3V after HFD. This is the first evidence that kisspeptin can be regulated by HFD and/or increased body weight. Next we demonstrated that leptin does not signal (via signal transducer and activator of transcription 3 or 5, or mammalian target of rapamycin) directly on kisspeptin-expressing neurons in the RP3V. Lastly, in leptin receptor-deficient mice, neither GnRH nor kisspeptin neurons were activated during a preovulatory-like GnRH/LH surge induction regime, indicating that leptin's actions on GnRH may be upstream of kisspeptin neurons. These data provide evidence that leptin's effects on reproductive function are regulated by kisspeptin neurons in both the ARC and RP3V, although in the latter site the effects are likely to be indirect.

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Metadata

Authors
Quennell, J. H., Howell, C. S., Roa, J., Augustine, R. A., Grattan, D. R., & Anderson, G. M.
Affiliations
  • Centre for Neuroendocrinology and Departments of Anatomy and Structural Biology (J.H.Q., C.S.H., R.A.A., D.R.G., G.M.A.), University of Otago School of Medical Sciences, Dunedin 9054, New Zealand
  • Physiology (J.R.), University of Otago School of Medical Sciences, Dunedin 9054, New Zealand
Venue
Endocrinology
Publisher
The Endocrine Society
Published
2011-02-15
Volume
152
Issue
4
Pages
1541-1550
ISSN
  • 0013-7227
  • 1945-7170
DOI
10.1210/en.2010-1100
Cited by
247
References
8
Language
en

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CoChat. (2026). Citation check: Leptin Deficiency and Diet-Induced Obesity Reduce Hypothalamic Kisspeptin Expression in Mice. https://app.cochat.ai/papers/10.1210/en.2010-1100
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Quennell, J. H., Howell, C. S., Roa, J., Augustine, R. A., Grattan, D. R., & Anderson, G. M. (2011). Leptin Deficiency and Diet-Induced Obesity Reduce Hypothalamic Kisspeptin Expression in Mice. Endocrinology. https://doi.org/10.1210/en.2010-1100

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