Journal article
Mitochondrial Lipid Oxidation is Impaired in Cultured Myotubes from Obese Humans
International journal of obesity (2005), Vol.36(8), pp.1025-1031
10/25/2011
DOI: 10.1038/ijo.2011.201
PMCID: PMC3848508
PMID: 22024640
Abstract
Objective: The skeletal muscle of obese humans is characterized by an inability to appropriately respond to alterations in substrate availability. The purpose of this study was to determine if this metabolic inflexibility with obesity is retained in mitochondria of human skeletal muscle cells raised in culture (HSkMC) and to identify potential mechanisms involved.Design: Mitochondrial respiration was measured in permeabilized myotubes cultured from lean and obese individuals before and after a 24-h lipid incubation.Results: Mitochondrial respiration (state 3) in the presence of lipid substrate (palmitoyl carnitine) increased by almost twofold after lipid incubation in HSkMC from lean, but not obese subjects, indicative of metabolic inflexibility with obesity. The 24-h lipid incubation increased mitochondrial DNA (mtDNA) copy number in HSkMC from lean subjects by 16% (P0.05); conversely, mtDNA copy number decreased in myotubes cultured from obese individuals (13%, P0.06). When respiration data were normalized to mtDNA copy number and other indices of mitochondrial content (COX-IV protein content and CS activity), the significant treatment effects of lipid incubation persisted in the lean subjects, suggesting concomitant alterations in mitochondrial function; no similar adjustment was evident in HSkMC from obese individuals.Conclusion: These data indicate that the skeletal muscle of obese individuals inherently lacks metabolic flexibility in response to lipid exposure, which consists of an inability to increase mitochondrial respiration in the presence of lipid substrate and perhaps by an inability to induce mitochondrial proliferation. © 2012 Macmillan Publishers Limited. All rights reserved.
Details
- Title: Subtitle
- Mitochondrial Lipid Oxidation is Impaired in Cultured Myotubes from Obese Humans
- Creators
- Kristen E. Boyle - East Carolina UniversityDonghai Zheng - East Carolina UniversityEthan J. Anderson - East Carolina UniversityP. Darrell Neufer - East Carolina UniversityJoseph A. Houmard - East Carolina University
- Resource Type
- Journal article
- Publication Details
- International journal of obesity (2005), Vol.36(8), pp.1025-1031
- DOI
- 10.1038/ijo.2011.201
- PMID
- 22024640
- PMCID
- PMC3848508
- NLM abbreviation
- Int J Obes (Lond)
- ISSN
- 0307-0565
- eISSN
- 1476-5497
- Grant note
- R01 AG025205 || AG / National Institute on Aging : NIA R01 DK074825 || DK / National Institute of Diabetes and Digestive and Kidney Diseases : NIDDK
- Language
- English
- Date published
- 10/25/2011
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics; Fraternal Order of Eagles Diabetes Research Center; Health, Sport, and Human Physiology
- Record Identifier
- 9984366041102771
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