title: Regulation of cardiac and skeletal muscle malonyl-CoA decarboxylase by fatty acids.
abstract: Malonyl-CoA decarboxylase (MCD) catalyzes the degradation of malonyl-CoA, an important modulator of fatty acid oxidation. We hypothesized that increased fatty acid availability would increase the expression and activity of heart and skeletal muscle MCD, thereby promoting fatty acid utilization. The results show that high-fat feeding, fasting, and streptozotocin-induced diabetes all significantly increased the plasma concentration of nonesterified fatty acids, with a concomitant increase in both rat heart and skeletal muscle MCD mRNA. Upon refeeding of fasted animals, MCD expression returned to basal levels. Fatty acids are known to activate peroxisome proliferator-activated receptor-alpha (PPARalpha). Specific PPARalpha stimulation, through Wy-14643 treatment, significantly increased the expression of MCD in heart and skeletal muscle. Troglitazone, a specific PPARgamma agonist, decreased MCD expression. The sensitivity of MCD induction by fatty acids and Wy-14643 was soleus > extensor digitorum longus > heart. High plasma fatty acids consistently increased MCD activity only in solei, whereas MCD activity in the heart actually decreased with high-fat feeding. Pressure overload-induced cardiac hypertrophy, in which PPARalpha expression is decreased (and fatty acid oxidation is decreased), resulted in decreased MCD mRNA and activity, an effect that was dependent on fatty acids. The results suggest that fatty acids induce the expression of MCD in rat heart and skeletal muscle. Additional posttranscriptional mechanisms regulating MCD activity appear to exist.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, University of Texas-Houston Medical School, Houston, TX 77030, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Young
authors.forename: G W
authors.initials: GW
authors.lastname: Goodwin
authors.forename: J
authors.initials: J
authors.lastname: Ying
authors.forename: P
authors.initials: P
authors.lastname: Guthrie
authors.forename: C R
authors.initials: CR
authors.lastname: Wilson
authors.forename: F A
authors.initials: FA
authors.lastname: Laws
authors.forename: H
authors.initials: H
authors.lastname: Taegtmeyer
mesh_terms: D000818:Animals; D001011:Aorta; D001794:Blood Pressure; D001835:Body Weight; D002262:Carboxy-Lyases / Q000235:genetics* / Q000378:metabolism; D002839:Chromans / Q000494:pharmacology; D003250:Constriction; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology; D004041:Dietary Fats / Q000008:administration & dosage; D005215:Fasting; D005227:Fatty Acids / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005502:Food; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006321:Heart / Q000033:anatomy & histology; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology*; D009206:Myocardium / Q000201:enzymology*; D009929:Organ Size; D011743:Pyrimidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000378:metabolism; D000077288:Troglitazone
chemical_list: D002839:Chromans; D004041:Dietary Fats; D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D011743:Pyrimidines; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; C006253:pirinixic acid; D002262:Carboxy-Lyases; C021532:malonyl-CoA decarboxylase; D000077288:Troglitazone