Oxidation of intramyocellular lipids is dependent on mitochondrial function and the availability of extracellular fatty acids

Eva Corpeleijn*, Nina P. Hessvik, Siril S. Bakke, Klaus Levin, Ellen E. Blaak, G. Hege Thoresen, Michael Gaster, Arild C. Rustan

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

22 Citaten (Scopus)

Samenvatting

Corpeleijn E, Hessvik NP, Bakke SS, Levin K, Blaak EE, Thoresen GH, Gaster M, Rustan AC. Oxidation of intramyocellular lipids is dependent on mitochondrial function and the availability of extracellular fatty acids. Am J Physiol Endocrinol Metab 299: E14-E22, 2010. First published May 4, 2010; doi:10.1152/ajpendo.00187.2010.-Obesity and insulin resistance are related to both enlarged intramyocellular triacylglycerol stores and accumulation of lipid intermediates. We investigated how lipid overflow can change the oxidation of intramyocellular lipids (ICLOX) and intramyocellular lipid storage (ICL). These experiments were extended by comparing these processes in primary cultured myotubes established from healthy lean and obese type 2 diabetic (T2D) individuals, two extremes in a range of metabolic phenotypes. ICLs were prelabeled for 2 days with 100 mu M [C-14] oleic acid (OA). ICLOX was studied using a (CO2)-C-14 trapping system and measured under various conditions of extracellular OA (5 or 100 mu M) and glucose (0.1 or 5.0 mM) and the absence or presence of mitochondrial uncoupling [carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP)]. First, increased extracellular OA availability (5 vs. 100 mu M) reduced ICLOX by 37%. No differences in total lipolysis were observed between low and high OA availability. Uncoupling with FCCP restored ICLOX to basal levels during high OA availability. Mitochondrial mass was positively related to ICLOX, but only in myotubes from lean individuals. In all, a lower mitochondrial mass and lower ICLOX were related to a higher cell-associated OA accumulation. Second, myotubes established from obese T2D individuals showed reduced ICLOX. ICLOX remained lower during uncoupling (P <0.001), even with comparable mitochondrial mass, suggesting decreased mitochondrial function. Furthermore, the variation in ICLOX in vitro was significantly related to the in vivo fasting respiratory quotient of all subjects (P <0.02). In conclusion, the rate of ICLOX is dependent on the availability of extracellular fatty acids and mitochondrial function rather than mitochondrial mass.

Originele taal-2English
Pagina's (van-tot)E14-E22
Aantal pagina's9
TijdschriftAmerican Journal of Physiology - Endocrinology and Metabolism
Volume299
Nummer van het tijdschrift1
DOI's
StatusPublished - jul-2010

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