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A null mutation in H-FABP only partially inhibits skeletal muscle fatty acid metabolism

¹Department of Pathobiology, College of Veterinary Medicine, Texas A & M University, College Station, Texas 77843; ²Department of Physiology, Maastricht University, 6200 MD Maastricht, The Netherlands; Departments of ³Biology and ⁴Kinesiology and Health Sciences, York University, Toronto, Ontario M3J 1P3; and ⁵Department of Human Biology and Nutritional Sciences, University of Guelph, Guelph, Ontario, N1G 2W1 Canada

Submitted 9 February 2003 ; accepted in final form 25 April 2003

The low-molecular-mass, cytosolic heart-type fatty acid-binding protein (H-FABP) is thought to be required for shuttling FA through the cytosol. Therefore, we examined the effects of an H-FABP-null mutation on FA and carbohydrate metabolism in isolated soleus muscle at rest and during a period of increased metabolic demand (30-min contraction). There were lower concentrations of creatine phosphate (-41%), ATP (-22%), glycogen (-34%), and lactate (-31%) (P < 0.05) in H-FABP-null soleus muscles, but no differences in citrate synthase and -3-hydroxyacyl-CoA dehydrogenase activities or in the intramuscular triacylglycerol (TAG) depots. There was a 43% increase in subsarcolemmal mitochondria in H-FABP-null solei. FA transport was reduced by 30% despite normal content of sarcolemmal long-chain fatty acid transporters fatty acid translocase/CD36 and plasma membrane-associated FABP transport proteins. Compared with wild-type soleus muscles, the H-FABP-null muscles at rest hydrolyzed less TAG (-22%), esterified less TAG (-49%), and oxidized less palmitate (-71%). The H-FABP-null soleus muscles retained a substantial capacity to increase FA metabolism during contraction (TAG esterification by +72%, CO₂ production by +120%), although these rates remained lower (TAG esterification -26% and CO₂ production -64%) than in contracting wild-type soleus muscles. Glycogen utilization during 30 min of contraction did not differ, whereas glucose oxidation was lower at rest (-24%) and during contraction (-32%) in H-FABP-null solei. Although these studies demonstrate that the absence of H-FABP alters rates of FA metabolism, it is also apparent that glucose oxidation is downregulated. The substantial increase in FA metabolism in contracting H-FABP-null muscle may indicate that other FABPs are also present, a possibility that we were not able to completely eliminate.

palmitate; esterification; oxidation; soleus; glucose

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