The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
Leptin selectively decreases visceral adiposity and enhances insulin action
Open accessAbstract
Intraabdominal adiposity and insulin resistance are risk factors for diabetes mellitus, dyslipidemia, arteriosclerosis, and mortality. Leptin, a fat-derived protein encoded by the ob gene, has been postulated to be a sensor of energy storage in adipose tissue capable of mediating a feedback signal to sites involved in the regulation of energy homeostasis. Here, we provide evidence for specific effects of leptin on fat distribution and in vivo insulin action. Leptin (LEP) or vehicle (CON) was administered by osmotic minipumps for 8 d to pair-fed adult rats. During the 8 d of the study, body weight and total fat mass decreased similarly in LEP and in CON. However, while moderate calorie restriction (CON) resulted in similar decreases in whole body (by 20%) and visceral (by 21%) fat, leptin administration led to a specific and marked decrease (by 62%) in visceral adiposity. During physiologic hyperinsulinemia (insulin clamp), leptin markedly enhanced insulin action on both inhibition of hepatic glucose production and stimulation of glucose uptake. Finally, leptin exerted complex effects on the hepatic gene expression of key metabolic enzymes and on the intrahepatic partitioning of metabolic fluxes, which are likely to represent a defense against excessive storage of energy in adipose depots. These studies demonstrate novel actions of circulating leptin in the regulation of fat distribution, insulin action, and hepatic gene expression and suggest that it may play a role in the pathophysiology of abdominal obesity and insulin resistance.
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“High leptin levels may lead to IR in nonobese PCOS patients by promoting the following events: (i) inhibition of phosphoenolpyruvate carboxykinase, causing decreased hepatic glucose oxidation and increased hepatic glycogen reserve; (ii) fat deposition in skeletal muscle cells; (iii) fat breakdown and free fatty acid production; and (iv) direct inhibition of basal insulin secretion and glucose-stim”
From Circulating Adipokine Levels in Nonobese Women with Polycystic Ovary Syndrome and in Nonobese Control Women: A Systematic Review and Meta-Analysis (2021) · cites this paper as [34]
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Cites
Positional cloning of the mouse obese gene and its human homologue
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Serum Immunoreactive-Leptin Concentrations in Normal-Weight and Obese Humans
Considine, R. V., Sinha, M. K., Heiman, M. L., Kriauciunas, A., Stephens, T. W., Nyce, M. R., Ohannesian, J. P., Marco, C. C., McKee, L. J., Bauer, T. L., et al. (1996) · New England Journal of Medicine · doi:10.1056/nejm199602013340503 · Cited by 6,326
Weight-Reducing Effects of the Plasma Protein Encoded by the obese Gene
Halaas, J. L., Gajiwala, K. S., Maffei, M., Cohen, S. L., Chait, B. T., Rabinowitz, D., Lallone, R. L., Burley, S. K., & Friedman, J. M. (1995) · Science · doi:10.1126/science.7624777 · Cited by 4,451
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Identification and expression cloning of a leptin receptor, OB-R.
Tartaglia, L. A., Dembski, M., Weng, X., Deng, N., Culpepper, J., Devos, R., Richards, G. J., Campfield, L. A., Clark, F. T., Deeds, J., et al. (1995) · Cell · doi:10.1016/0092-8674(95)90151-5 · Cited by 3,496
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Schwartz, M. W., Seeley, R. J., Campfield, L. A., Burn, P., & Baskin, D. G. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118891 · Cited by 1,499
Positional cloning of the mouse obese gene and its human homologue
Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., & Friedman, J. M. (1995) · Nature · doi:10.1038/374479a0 · Cited by 1,125
Metabolic Implications of Body Fat Distribution
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Nonalcoholic Steatohepatitis: Summary of An Aasld Single Topic Conference
Neuschwander‐Tetri, B. A., & Caldwell, S. H. (2003) · Hepatology · doi:10.1053/jhep.2003.50193 · Cited by 2,166
The stomach is a source of leptin
Bado, A., Levasseur, S., Attoub, S., Kermorgant, S., Laigneau, J., Bortoluzzi, M.-N., Moizo, L., Lehy, T., Guerre-Millo, M., MARCHAND‐BRUSTEL, Y. L., et al. (1998) · Nature · doi:10.1038/29547 · Cited by 1,242
“On the other hand, leptin could enter the liver in quantities sufficiently large to affect glucose production and uptake as well as the hepatic expression of genes encoding key metabolic enzyme”
BackgroundManna, P., & Jain, S. K. (2015) · Metabolic Syndrome and Related Disorders · doi:10.1089/met.2015.0095 · Cited by 1,211
Wolf, G., Chen, S., Han, D. C., & Ziyadeh, F. N. (2002) · American Journal of Kidney Diseases · doi:10.1053/ajkd.2002.29865 · Cited by 870
Obesity and Obstructive Sleep Apnea: Pathogenic Mechanisms and Therapeutic Approaches
Schwartz, A. R., Patil, S. P., Laffan, A. M., Polotsky, V., Schneider, H., & Smith, P. L. (2008) · Proceedings of the American Thoracic Society · doi:10.1513/pats.200708-137mg · Cited by 730
Metadata
- Authors
- Barzilai, N., Wang, J., Massilon, D., Vuguin, P., Hawkins, M., & Rossetti, L.
- Affiliations
- Albert Einstein College of Medicine (US)
- Corresponding author
- Rossetti, L
- Venue
- Journal of Clinical Investigation
- Published
- 1997-12-15
- Volume
- 100
- Issue
- 12
- Pages
- 3105-3110
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC508523
- OpenAlex
- W2152760501
- Cited by
- 335
- References
- 34
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2022: 2 · 2021: 7 · 2020: 8 · 2019: 3 · 2018: 4 · 2017: 7 · 2016: 5 · 2015: 12 · 2014: 10 · 2013: 6 · 2012: 11
- FWCI
- 6.31
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Amgen
- Medical Research Council Canada
- National Institutes of Health
- Medical Research Council
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-48321, DK20541, DK-45024)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Keywords
- leptin, visceral fat, intra-abdominal fat, insulin action, insulin resistance, abdominal obesity, body fat distribution, hepatic glucose production, hepatic glucose uptake, hepatic gene expression, energy homeostasis, caloric restriction, hyperinsulinemia
- MeSH terms
- Adipose Tissue, Animals, Blood Glucose, Body Weight, Eating, Glucose, Insulin, Liver, Male, Proteins, Recombinant Proteins, Viscera, Gene Expression, Rats, Sprague-Dawley, Leptin, Mice, Rats
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