Triacylglycerol accumulation in human obesity and type 2 diabetes is associated with increased rates of skeletal muscle fatty acid transport and increased sarcolemmal FAT/CD36.
We examined whether, in human obesity and type 2 diabetes, long chain fatty acid (LCFA) transport into skeletal muscle is upregulated and contributes to an excess intramuscular triacylglycerol accumulation. In giant sarcolemmal vesicles prepared from human skeletal muscle, LCFA transport rates were upregulated approximately 4-fold and were associated with an increased intramuscular triacylglycerol content in obese individuals and in type 2 diabetics. In these individuals, the increased sarcolemmal LCFA transport rate was not associated with an altered expression of FAT/CD36 or FABPpm. Instead, the increase in the LCFA transport rate was associated with an increase in sarcolemmal FAT/CD36 but not sarcolemmal FABPpm. Rates of fatty acid esterification were increased threefold in isolated human muscle strips obtained from obese subjects, while concomitantly rates of fatty acid oxidation were not altered. Thus, the increased rate of fatty acid transport may contribute to the increased rates of triacylglycerol accumulation in human skeletal muscle. The altered FAT/CD36 trafficking in muscle from obese subjects and type 2 diabetics juxtaposes the known alterations in GLUT4 trafficking, i.e., GLUT4 is known to be retained in its intracellular depots while FAT/CD36 is retained at the sarcolemma. This redistribution of FAT/CD36 to the sarcolemma may contribute to the etiology of insulin resistance in human muscle, and hence, FAT/CD36 provides another potential therapeutic target for the prevention and/or treatment of insulin resistance.
Bonen
Arend
A
Department of Human Biology and Nutritional Sciences, University of Guelph, Guelph, Ontario, N1G 2W1, Canada. abonen@uogulph.ca
Parolin
Michelle L
ML
Steinberg
Gregory R
GR
Calles-Escandon
Jorge
J
Tandon
Narendra N
NN
Glatz
Jan F C
JF
Luiken
Joost J F P
JJ
Heigenhauser
George J F
GJ
Dyck
David J
DJ
D000368:Aged; D001692:Biological Transport; D015992:Body Mass Index; D018955:CD36 Antigens / Q000032:analysis / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D019308:Palmitic Acid / Q000378:metabolism; D012508:Sarcolemma / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism*
D018955:CD36 Antigens; D002352:Carrier Proteins; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D014280:Triglycerides; D019308:Palmitic Acid