Cited by 552Regulation of Appetite and ObesityHypothalamic control of reproductive hormonesAdipokines, Inflammation, and Metabolic Diseases

Gonadal Hormones Determine Sensitivity to Central Leptin and Insulin

Open access
Clegg, Deborah J., Brown, Lynda M., Woods, Stephen C., Benoit, Stephen C.·2006·Diabetes

Abstract

Males have proportionally more visceral fat and are more likely to develop complications associated with obesity than females, and the male brain is relatively more sensitive to the catabolic action of insulin and less sensitive to that of leptin than the female brain. To understand the underlying mechanism, we manipulated estrogen through ovariectomy (OVX) and estradiol administration. Rats with relatively high systemic estrogen (intact females and OVX females and males administered estrogen subcutaneously) were significantly more sensitive to leptin’s anorexic action in the brain (i3vt), as well as significantly less sensitive to insulin’s i3vt action, than intact males. Administering estradiol directly into the brain of our females increased i3vt leptin sensitivity while decreasing i3vt insulin sensitivity and changed the body fat distribution of our females to resemble that of intact females. These data indicate that estrogen acts within the brain to increase leptin sensitivity, decrease insulin sensitivity, and favor subcutaneous over visceral fat.

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Crossref · 10.2337/diabetes.55.04.06.db05-1339

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  • Estrogen increases leptin sensitivity by controlling the expression of leptin-specific receptors.

    “Estrogen increases leptin sensitivity by controlling the expression of leptin-specific receptors [130–132].”
  • Studies in rodents suggest that systemic oestrogen may decrease the hypophagic effect of central insulin.

    “although studies in rodents suggest that systemic oestrogen may decrease the hypophagic effect of central insulin”

    From Intranasal insulin (2021) · cites this paper as [64]

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  1. Flier JS: Obesity wars: molecular progress confronts an expanding epidemic (Review). Cell 11:6337-350, 2004

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Authors
Clegg, D. J., Brown, L. M., Woods, S. C., & Benoit, S. C.
Affiliations
University of Cincinnati (US)
Venue
Diabetes
Published
2006-04-01
Volume
55
Issue
4
Pages
978-987
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
OpenAlex
W2061084753
Cited by
552
References
106
Citations by year
2026: 10 · 2025: 14 · 2024: 12 · 2023: 14 · 2022: 26 · 2021: 20 · 2020: 30 · 2019: 32 · 2018: 30 · 2017: 31 · 2016: 39 · 2015: 24 · 2014: 32 · 2013: 37 · 2012: 33
FWCI
13.73
Type
journal article
Language
en
Open access
Locations
  • Diabetes (publishedVersion)
  • PubMed (publishedVersion)
  • UCLA - Biblioteca de Ciencias de la Salud (submittedVersion)
Funders
  • University of Cincinnati
  • National Institutes of Health (DK56863)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK17844, DK54080, R01DK054080, P01DK056863, DK-56863)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Keywords
gonadal hormones, estrogen, leptin sensitivity, insulin sensitivity, ovariectomy, estradiol, visceral fat, subcutaneous adipose tissue, sex differences, brain, body fat distribution, obesity
MeSH terms
Animals, Body Weight, Energy Intake, Estradiol, Female, Insulin, Male, Orchiectomy, Ovariectomy, Sex Characteristics, Rats, Long-Evans, Leptin, Rats

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