Leptin increases FA oxidation in lean but not obese human skeletal muscle: evidence of peripheral leptin resistance
Abstract
The adipocyte-derived hormone leptin has been shown to acutely increase fatty acid (FA) oxidation and decrease esterification in resting rodent skeletal muscle. However, the effects of leptin on human skeletal muscle FA metabolism are completely unknown. In these studies, we have utilized an isolated human skeletal muscle preparation combined with the pulse-chase technique to measure FA metabolism with and without leptin in lean and obese human skeletal muscle. Under basal conditions (in the absence of leptin), muscle from the obese demonstrated significantly elevated levels of total FA uptake (+72%, P = 0.038) and enhanced rates of FA esterification into triacylglycerol (+102%, P = 0.042) compared with lean subjects. In the presence of leptin, lean muscle had elevated rates of endogenous (+103%, P = 0.01) and exogenous (+150%, P = 0.03) palmitate oxidation. When the ratio of esterification to exogenous oxidation was examined, leptin reduced this ratio (−47%, P = 0.032), demonstrating the increased partitioning of FA toward oxidation and away from storage. Contrary to these findings in lean muscle, leptin had no effect on FA metabolism in skeletal muscle of the obese. This study provides the first evidence that leptin increases FA oxidation in skeletal muscle of lean, but not obese humans, thus demonstrating the development of leptin resistance in obese human skeletal muscle.
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Several studies report decreased fat oxidation in skeletal muscle independent of plasma free fatty acid concentration.
“Several studies have reported decreased fat oxidation in skeletal muscle, independent of the plasma FFA concentration [100–102].”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [102]
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Self-citation
- Authors
- Steinberg, G. R., Parolin, M. L., Heigenhauser, G. J. F., & Dyck, D. J.
- Affiliations
- University of Guelph (CA)
- McMaster University (CA)
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2002-07-01
- Volume
- 283
- Issue
- 1
- Pages
- E187-E192
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- OpenAlex
- W2111231879
- Cited by
- 207
- References
- 27
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 6 · 2023: 1 · 2022: 6 · 2021: 3 · 2020: 5 · 2019: 5 · 2018: 3 · 2017: 5 · 2016: 3 · 2015: 6 · 2014: 6 · 2013: 11 · 2012: 14
- FWCI
- 7.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- leptin, fatty acid oxidation, skeletal muscle, leptin resistance, obesity, fatty acid esterification, triglyceride synthesis, fatty acid uptake, palmitate oxidation, human skeletal muscle, energy allocation
- MeSH terms
- Biopsy, Drug Resistance, Esterification, Fatty Acids, Female, Humans, Middle Aged, Obesity, Oxidation-Reduction, Palmitates, Thinness, Body Mass Index, Muscle, Skeletal, Leptin, In Vitro Techniques
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