The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
Differential Sensitivity to Central Leptin and Insulin in Male and Female Rats
Abstract
The distribution of fat in the body differs between the male and female sexes and is associated with the relative secretion of the two “adiposity” hormones leptin and insulin. We now report that the brains of male and female rats are differentially sensitive to the catabolic actions of small doses of these two hormones. Leptin (1 or 3.5 μg/2 μl) or saline (2 μl) was administered into the third cerebral ventricle of age- and weight-matched male and female rats. Leptin significantly reduced food intake in female and male rats over 4 h; however, leptin reduced 24-h intake in female but not in male rats. When the same rats were administered insulin (1 or 4 mU/2 μl) or saline (2 μl), male but not female rats had a robust reduction in food intake over 24 h. Previous research demonstrates the melanocortins are a central mediator of the effects of both leptin and insulin. However, we found no sex differences in sensitivity to the melanocortin agonist MTII (0.01, 0.1, 0.3, and 1.0 nmol/2 μl). These results suggest that the sex differences in sensitivity to leptin and insulin at the doses that we injected occur upstream of the melanocortin receptors. Because insulin and leptin reflect different fat beds and are differentially distributed in the male and female sexes, the implication is that the male and female sexes regulate adiposity-relevant parameters differently.
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In the citing paper
“Intracerebroventricular injection of insulin markedly reduced food intake in male rodents, whereas feeding was unaffected in female rodents23.”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [23]
In the citing paper
“Of note, experimental studies suggest considerable sex differences in brain insulin sensitivity.”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [23]
In the citing paper
“Male rats, however, are more sensitive to the anorectic action of insulin injected in the brain [32], an observation that translates to humans.”
From Sex differences in metabolic homeostasis, diabetes, and obesity (2015) · cites this paper as [32]
In the citing paper
“Accordingly, female rats are more sensitive to the anorectic action of centrally injected leptin than males [32].”
From Sex differences in metabolic homeostasis, diabetes, and obesity (2015) · cites this paper as [32]
Citations
Cites
Central nervous system control of food intake
Schwartz, M. W., Woods, S. C., Porte, D., Seeley, R. J., & Baskin, D. G. (2000) · Nature · doi:10.1038/35007534 · Cited by 6,451
Self-citationOverweight and obesity in the United States: prevalence and trends, 1960–1994
Flegal, K., Carroll, M., Kuczmarski, R., & Johnson, C. (1998) · International Journal of Obesity · doi:10.1038/sj.ijo.0800541 · Cited by 3,045
Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome
Wajchenberg, B. L. (2000) · Endocrine Reviews · doi:10.1210/edrv.21.6.0415 · Cited by 2,961
Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus
Cowley, M. A., Smart, J. L., Rubinstein, M., Cerdán, M. G., Diano, S., Horvath, T. L., Cone, R. D., & Low, M. J. (2001) · Nature · doi:10.1038/35078085 · Cited by 2,356
Role of melanocortinergic neurons in feeding and the agouti obesity syndrome
Fan, W., Boston, B. A., Kesterson, R. A., Hruby, V. J., & Cone, R. D. (1997) · Nature · doi:10.1038/385165a0 · Cited by 1,924
Leptin enters the brain by a saturable system independent of insulin
Banks, W. A., Kastin, A. J., Huang, W., Jaspan, J. B., & Maness, L. M. (1996) · Peptides · doi:10.1016/0196-9781(96)00025-3 · Cited by 1,222
Signals That Regulate Food Intake and Energy Homeostasis
Woods, S. C., Seeley, R. J., Porte, D., & Schwartz, M. W. (1998) · Science · doi:10.1126/science.280.5368.1378 · Cited by 1,177
Self-citationLeptin Increases Hypothalamic Pro-opiomelanocortin mRNA Expression in the Rostral Arcuate Nucleus
Schwartz, M. W., Seeley, R. J., Woods, S. C., Weigle, D. S., Campfield, L. A., Burn, P., & Baskin, D. G. (1997) · Diabetes · doi:10.2337/diab.46.12.2119 · Cited by 879
Self-citationThe Obesity Epidemic Is a Worldwide Phenomenon
Popkin, B. M., & Doak, C. M. (2009) · Nutrition Reviews · doi:10.1111/j.1753-4887.1998.tb01722.x · Cited by 859
Proopiomelanocortin Neurons Are Direct Targets for Leptin in the Hypothalamus
Cheung, C. C., Clifton, D. K., & Steiner, R. A. (1997) · Endocrinology · doi:10.1210/endo.138.10.5570 · Cited by 769 · cited 8×
“DIABETES, VOL. 52, MARCH 2003 683 D ow nloaded from http://diabetesjournals.org/diabetes/article-pdf/52/3/682/373103/db0303000682.pdf by guest on 04 M arch 2022 I3vt leptin reduces food intake and body weight to a greater extent in female than male rats (experiment 2).”
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Sex and Gender Differences in Risk, Pathophysiology and Complications of Type 2 Diabetes Mellitus
Kautzky-Willer, A., Harreiter, J., & Pacini, G. (2016) · Endocrine Reviews · doi:10.1210/er.2015-1137 · Cited by 2,043
The role of estrogens in control of energy balance and glucose homeostasis
Mauvais-Jarvis, F., Clegg, D. J., & Hevener, A. L. (2013) · Endocrine Reviews · doi:10.1210/er.2012-1055 · Cited by 1,329
Self-citationAnimal models of obesity and diabetes mellitus
Kleinert, M., Clemmensen, C., Hofmann, S. M., Moore, M. C., Renner, S., Woods, S. C., Huypens, P., Beckers, J., de Angelis, M. H., Schürmann, A., et al. (2018) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2017.161 · Cited by 893
Self-citationIntranasal insulin improves memory in humans
Benedict, C., Hallschmid, M., Hatke, A., Schultes, B., Fehm, H. L., Born, J., & Kern, W. (2004) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2004.04.003 · Cited by 699
Sex differences in metabolic homeostasis, diabetes, and obesity
Mauvais-Jarvis, F. (2015) · Biology of Sex Differences · doi:10.1186/s13293-015-0033-y · Cited by 626
“Male rats, however, are more sensitive to the anorectic action of insulin injected in the brain [32], an observation that translates to humans.”
Background
Metadata
- Authors
- Clegg, D. J., Riedy, C. A., Smith, K. A. B., Benoit, S. C., & Woods, S. C.
- Affiliations
- University of Cincinnati (US)
- University of Washington (US)
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2003-03-01
- Volume
- 52
- Issue
- 3
- Pages
- 682-687
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2007895806
- Cited by
- 332
- References
- 42
- Citations by year
- 2026: 1 · 2025: 8 · 2024: 7 · 2023: 8 · 2022: 13 · 2021: 19 · 2020: 23 · 2019: 10 · 2018: 15 · 2017: 15 · 2016: 18 · 2015: 16 · 2014: 15 · 2013: 25 · 2012: 14
- FWCI
- 5.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Cincinnati
- National Institutes of Health
- 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 › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- leptin, insulin, sex differences, dietary intake, melanocortin peptides, melanotan II, melanocortin receptors, adiposity, rats
- MeSH terms
- alpha-MSH, Animals, Body Composition, Body Weight, Brain, Eating, Female, Injections, Intraventricular, Insulin, Male, Sex Characteristics, Receptors, Corticotropin, Rats, Long-Evans, Leptin, Receptors, Melanocortin, Rats
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