A null mutation in skeletal muscle FAT/CD36 reveals its essential role in insulin- and AICAR-stimulated fatty acid metabolism.
Fatty acid translocase (FAT)/CD36 is involved in regulating the uptake of long-chain fatty acids into muscle cells. However, the contribution of FAT/CD36 to fatty acid metabolism remains unknown. We examined the role of FAT/CD36 on fatty acid metabolism in perfused muscles (soleus and red and white gastrocnemius) of wild-type (WT) and FAT/CD36 null (KO) mice. In general, in muscles of KO mice, 1) insulin sensitivity and 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) sensitivity were normal, 2) key enzymes involved in fatty acid oxidation were altered minimally or not at all, and 3) except for an increase in soleus muscle FATP1 and FATP4, these fatty acid transporters were not altered in red and white gastrocnemius muscles, whereas plasma membrane-bound fatty acid binding protein was not altered in any muscle. In KO muscles perfused under basal conditions (i.e., no insulin, no AICAR), rates of hindquarter fatty acid oxidation were reduced by 26%. Similarly, in oxidative but not glycolytic muscles, the basal rates of triacylglycerol esterification were reduced by 40%. When muscles were perfused with insulin, the net increase in fatty acid esterification was threefold greater in the oxidative muscles of WT mice compared with the oxidative muscles in KO mice. With AICAR-stimulation, the net increase in fatty acid oxidation by hindquarter muscles was 3.7-fold greater in WT compared with KO mice. In conclusion, the present studies demonstrate that FAT/CD36 has a critical role in regulating fatty acid esterification and oxidation, particularly during stimulation with insulin or AICAR.
Bonen
Arend
A
Department of Human Health and Nutritional Science, University of Guelph, Guelph, Ontario, Canada N1G 2W1. abonen@uoguelph.ca
Han
Xiao-Xia
XX
Habets
Daphna D J
DD
Febbraio
Maria
M
Glatz
Jan F C
JF
Luiken
Joost J F P
JJ
D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D018955:CD36 Antigens / Q000235:genetics*; D004075:Diglycerides / Q000378:metabolism; D004951:Esterification / Q000187:drug effects; D050612:Fatty Acid Transport Proteins / Q000378:metabolism; D005227:Fatty Acids / Q000097:blood / Q000378:metabolism*; D006003:Glycogen / Q000096:biosynthesis; D006614:Hindlimb; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D010084:Oxidation-Reduction; D010168:Palmitates / Q000378:metabolism / Q000493:pharmacokinetics; D010743:Phospholipids / Q000378:metabolism; D012265:Ribonucleotides / Q000494:pharmacology*; D014280:Triglycerides / Q000378:metabolism
D001786:Blood Glucose; D018955:CD36 Antigens; D004075:Diglycerides; D050612:Fatty Acid Transport Proteins; D005227:Fatty Acids; D007328:Insulin; D024101:Mitochondrial Proteins; D010168:Palmitates; D010743:Phospholipids; D012265:Ribonucleotides; C493569:Slc27a1 protein, mouse; C493572:Slc27a4 protein, mouse; D014280:Triglycerides; D000620:Aminoimidazole Carboxamide; D006003:Glycogen; C031143:AICA ribonucleotide