title: The long-term regulation of skeletal muscle pyruvate dehydrogenase kinase by dietary lipid is dependent on fatty acid composition.
abstract: The provision of a diet high in saturated and monounsaturated fat for 28 days evoked a significant (1.9-fold) increase in pyruvate-dehydrogenase kinase activity measured in isolated mitochondria from representative slow-twitch (oxidative) skeletal muscles (pooled soleus and adductor longus muscles) from adult rats. The increase observed in response to 28 days of high-fat feeding in slow-twitch skeletal muscle mitochondria was similar in magnitude to that observed in heart mitochondria. Pyruvate-dehydrogenase kinase activity was not increased in response to the provision of the high-fat diet in mitochondria prepared from a representative fast-twitch muscle (tibialis anterior), while the increases evoked by 28 days of high-fat feeding in cardiac and slow-twitch skeletal muscle were prevented by the replacement of 7% of the dietary fatty acids with long-chain omega-3 fatty acids from marine oil. Cardiac myocytes prepared from the high-fat-fed rats showed impaired responses of this enzyme to n-octanoate (1 mM) and N6,2-O-dibutyryladenosine 3',5'-monophosphate (50 microM) individually in cultured cardiac myocytes and of glucose uptake to insulin at low concentrations in freshly prepared cardiac myocytes, compared with control rats maintained on standard low-fat/high-carbohydrate diet. These impairments in responses to agonists were substantially improved by the inclusion of long-chain omega-3 fatty acids in the high-fat diet. The results indicate that pyruvate-dehydrogenase kinase activity in oxidative skeletal muscle is a target for longer-term regulation by high-fat feeding and that the fatty acid composition of the diet, rather than the fat content, is a key influence.
authors.affiliation: Department of Biochemistry, Queen Mary & Westfield, University of London, England.
authors.forename: L G
authors.initials: LG
authors.lastname: Fryer
authors.forename: K A
authors.initials: KA
authors.lastname: Orfali
authors.forename: M J
authors.initials: MJ
authors.lastname: Holness
authors.forename: E D
authors.initials: ED
authors.lastname: Saggerson
authors.forename: M C
authors.initials: MC
authors.lastname: Sugden
mesh_terms: D000818:Animals; D003994:Bucladesine / Q000008:administration & dosage; D002210:Caprylates / Q000008:administration & dosage; D002478:Cells, Cultured; D004041:Dietary Fats / Q000008:administration & dosage*; D005227:Fatty Acids / Q000008:administration & dosage / Q000737:chemistry*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage; D005260:Female; D007328:Insulin / Q000494:pharmacology; D008563:Membrane Lipids / Q000737:chemistry; D008929:Mitochondria, Heart / Q000201:enzymology; D008931:Mitochondria, Muscle / Q000201:enzymology; D018482:Muscle, Skeletal / Q000201:enzymology*; D009206:Myocardium / Q000166:cytology / Q000201:enzymology; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002210:Caprylates; D004041:Dietary Fats; D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D007328:Insulin; D008563:Membrane Lipids; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D003994:Bucladesine; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; C031492:octanoic acid