Gonadal Hormones Determine Sensitivity to Central Leptin and Insulin
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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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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].”
From Estrogen deficiency and the origin of obesity during menopause (2014) · cites this paper as [131]
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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“Additionally, subcutaneous adipose tissue, which accounts for a higher percentage of adipose tissue in females, secretes leptin, and the secreted leptin may activate CNS leptin receptors, and this may directly influence leptin-induced activation of the sympathetic nervous system.”
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Effect of Intranasal Insulin on Cognitive Function: A Systematic Review
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The role of hypothalamic estrogen receptors in metabolic regulation
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Insulin and Estrogen Independently and Differentially Reduce Macronutrient Intake in Healthy Men
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- Authors
- Clegg, D. J., Brown, L. M., Woods, S. C., & Benoit, S. C.
- Affiliations
- University of Cincinnati (US)
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- 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
- bronze
- doi.org
- 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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