FABPs as determinants of myocellular and hepatic fuel metabolism.
In vitro experiments and expression patterns have long suggested important roles for the genetically related cytosolic fatty acid binding proteins (FABPs) in lipid metabolism. However, evidence for such roles in vivo has become available only recently from genetic manipulation of FABP expression in mice. Here, we summarize the fuel-metabolic phenotypes of mice lacking the genes encoding heart-type FABP (H-/- mice) or liver-type FABP (L-/- mice). Cytosolic extracts from H-/- heart and skeletal muscle and from L-/- liver showed massively reduced binding of long chain fatty acids (LCFA) and, in case of L-/- liver, also of LCFA-CoA. Uptake, oxidation, and esterification LCFA, when measured in vivo and/or ex vivo, were markedly reduced in H-/- heart and muscle and in L-/- liver. The reduced LCFA oxidation in H-/- heart and L-/- liver was not due to reduced activity of PPARa, a fatty acid-sensitive transcription factor that determines the lipid-oxidative capacity in these organs. In H-/- mice, mechanisms of compensation were partially studied and included a redistribution of muscle mitochondria as well as increases of cardiac and skeletal muscle glucose uptakes and of hepatic ketogenesis. In skeletal muscle, the altered glucose uptake included decreased basal but increased insulin-dependent components. Metabolic compensation was only partial, however, since the H-/- mice showed decreased exercise tolerance. In conclusion, the recent studies established H- and L-FABP as major determinants of regional LCFA utilization; therefore the H-/- and L-/- mice are attractive models for studying principles of fuel selection and metabolic homeostasis.
Binas
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Department of Pathobiology, College of Vet. Medicine, Texas A&M University, College Station, TX 77843, USA. bbinas@cvm.tamu.edu
Erol
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E
D000818:Animals; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D008099:Liver / Q000378:metabolism*; D051379:Mice; D009132:Muscles / Q000378:metabolism*
D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D005947:Glucose