DOI: 10.1073/pnas.94.9.4637. Direct antidiabetic effect of leptin through triglyceride depletion of tissues

Direct antidiabetic effect of leptin through triglyceride depletion of tissues

10.1073/pnas.94.9.4637

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Leptin is currently believed to control body composition largely, if not entirely, via hypothalamic receptors that regulate food intake and thermogenesis. Here we demonstrate direct extraneural effects of leptin to deplete fat content of both adipocytes and nonadipocytes to levels far below those of pairfed controls. In cultured pancreatic islets, leptin lowered triglyceride (TG) content by preventing TG formation from free fatty acids (FFA) and by increasing FFA oxidation. In vivo hyperleptinemia, induced in normal rats by adenovirus gene transfer, depleted TG content in liver, skeletal muscle, and pancreas without increasing plasma FFA or ketones, suggesting intracellular oxidation. In islets of obese Zucker Diabetic Fatty rats with leptin receptor mutations, leptin had no effect in vivo or in vitro . The TG content was ≈20 times normal, and esterification capacity was increased 3- to 4-fold. Thus, in rats with normal leptin receptors but not in Zucker Diabetic Fatty rats, nonadipocytes and adipocytes esterify FFA, store them as TG, and later oxidize them intracellularly via an “indirect pathway” of intracellular fatty acid metabolism controlled by leptin. By maintaining insulin sensitivity and preventing islet lipotoxicity, this activity of leptin may prevent adipogenic diabetes.

Bibliography

Shimabukuro, M., Koyama, K., Chen, G., Wang, M.-Y., Trieu, F., Lee, Y., Newgard, C. B., & Unger, R. H. (1997). Direct antidiabetic effect of leptin through triglyceride depletion ofâtissues. Proceedings of the National Academy of Sciences, 94(9), 4637â4641.

Authors 8

Michio Shimabukuro (first)
Kazunori Koyama (additional)
Guoxun Chen (additional)
May-Yun Wang (additional)
Falguni Trieu (additional)
Young Lee (additional)
Christopher B. Newgard (additional)
Roger H. Unger (additional)

References 27 Referenced 486

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:35 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 4 p.m.)
Indexed	1 month ago (Aug. 5, 2025, 9:05 a.m.)
Issued	28 years, 4 months ago (April 29, 1997)
Published	28 years, 4 months ago (April 29, 1997)
Published Online	28 years, 4 months ago (April 29, 1997)
Published Print	28 years, 4 months ago (April 29, 1997)

Funders 0

None

BibTeX

@article{Shimabukuro_1997, title={Direct antidiabetic effect of leptin through triglyceride depletion of tissues}, volume={94}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.94.9.4637}, DOI={10.1073/pnas.94.9.4637}, number={9}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Shimabukuro, Michio and Koyama, Kazunori and Chen, Guoxun and Wang, May-Yun and Trieu, Falguni and Lee, Young and Newgard, Christopher B. and Unger, Roger H.}, year={1997}, month=apr, pages={4637–4641} }

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