Lipid metabolism and adipokine levels in fatty acid-binding protein null and transgenic mice.
Fatty acid-binding proteins (FABPs) facilitate the diffusion of fatty acids within cellular cytoplasm. Compared with C57Bl/6J mice maintained on a high-fat diet, adipose-FABP (A-FABP) null mice exhibit increased fat mass, decreased lipolysis, increased muscle glucose oxidation, and attenuated insulin resistance, whereas overexpression of epithelial-FABP (E-FABP) in adipose tissue results in decreased fat mass, increased lipolysis, and potentiated insulin resistance. To identify the mechanisms that underlie these processes, real-time PCR analyses indicate that the expression of hormone-sensitive lipase is reduced, while perilipin A is increased in A-FABP/aP2 null mice relative to E-FABP overexpressing mice. In contrast, de novo lipogenesis and expression of genes encoding lipoprotein lipase, CD36, long-chain acyl-CoA synthetase 5, and diacylglycerol acyltransferase are increased in A-FABP/aP2 null mice relative to E-FABP transgenic animals. Consistent with an increase in de novo lipogenesis, there was an increase in adipose C16:0 and C16:1 acyl-CoA pools. There were no changes in serum free fatty acids between genotypes. Serum levels of resistin were decreased in the E-FABP transgenic mice, whereas serum and tissue adiponectin were increased in A-FABP/aP2 null mice and decreased in E-FABP transgenic animals; leptin expression was unaffected. These results suggest that the balance between lipolysis and lipogenesis in adipocytes is remodeled in the FABP null and transgenic mice and is accompanied by the reprogramming of adipokine expression in fat cells and overall changes in plasma adipokines.
Hertzel
Ann V
AV
Dept. of Biochemistry, Molecular Biology, and Biophysics, Univ. of Minnesota, 321 Church St. SE, Minneapolis, MN 55455, USA.
Smith
Lisa Ann
LA
Berg
Anders H
AH
Cline
Gary W
GW
Shulman
Gerald I
GI
Scherer
Philipp E
PE
Bernlohr
David A
DA
D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D052242:Adiponectin / Q000097:blood; D000273:Adipose Tissue / Q000201:enzymology / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins; D004822:Epididymis / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D015870:Gene Expression / Q000235:genetics; D020738:Leptin / Q000097:blood; D050356:Lipid Metabolism / Q000235:genetics*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D036361:Peptide Hormones / Q000097:blood* / Q000378:metabolism; D000070778:Perilipin-1; D010750:Phosphoproteins / Q000235:genetics; D052243:Resistin / Q000097:blood
D052242:Adiponectin; D002352:Carrier Proteins; C493411:Fabp4 protein, mouse; C082667:Fabp5 protein, mouse; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D005231:Fatty Acids, Unsaturated; D020738:Leptin; D009363:Neoplasm Proteins; D036361:Peptide Hormones; D000070778:Perilipin-1; D010750:Phosphoproteins; D052243:Resistin