title: Long-chain acyl-CoA esters as indicators of lipid metabolism and insulin sensitivity in rat and human muscle.
abstract: Long-chain acyl-CoAs (LCACoA) are an activated lipid species that are key metabolites in lipid metabolism; they also have a role in the regulation of other cellular processes. However, few studies have linked LCACoA content in rat and human muscle to changes in nutritional status and insulin action. Fasting rats for 18 h significantly elevated the three major LCACoA species in muscle (P < 0.001), whereas high-fat feeding of rats with a safflower oil (18:2) diet produced insulin resistance and increased total LCACoA content (P < 0.0001) by specifically increasing 18:2-CoA. The LCACoA content of red muscle from rats (4-8 nmol/g) was 4- to 10-fold higher than adipose tissue (0.4-0.9 nmol/g, P < 0.001), suggesting that any contamination of muscle samples with adipocytes would contribute little to the LCACoA content of muscle. In humans, the LCACoA content of muscle correlated significantly with a measure of whole body insulin action in 17 male subjects (r(2) = 0.34, P = 0.01), supporting a link between muscle lipid metabolism and insulin action. These results demonstrate that the LCACoA pool reflects lipid metabolism and nutritional state in muscle. We conclude that the LCACoA content of muscle provides a direct index of intracellular lipid metabolism and its links to insulin action, which, unlike triglyceride content, is not subject to contamination by closely associated adipose tissue.
authors.affiliation: Garvan Institute of Medical Research, St. Vincent's Hospital, Sydney, New South Wales, Australia. b.ellis@garvan.unsw.edu.au
authors.forename: B A
authors.initials: BA
authors.lastname: Ellis
authors.forename: A
authors.initials: A
authors.lastname: Poynten
authors.forename: A J
authors.initials: AJ
authors.lastname: Lowy
authors.forename: S M
authors.initials: SM
authors.lastname: Furler
authors.forename: D J
authors.initials: DJ
authors.lastname: Chisholm
authors.forename: E W
authors.initials: EW
authors.lastname: Kraegen
authors.forename: G J
authors.initials: GJ
authors.lastname: Cooney
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism; D000368:Aged; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003066:Coenzyme A Ligases / Q000378:metabolism; D004952:Esters; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D050356:Lipid Metabolism; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000378:metabolism
chemical_list: D000214:Acyl Coenzyme A; D001786:Blood Glucose; D004952:Esters; D007328:Insulin; D014280:Triglycerides; D003066:Coenzyme A Ligases