Increased glucose oxidation in H-FABP null soleus muscle is associated with defective triacylglycerol accumulation and mobilization, but not with the defect of exogenous fatty acid oxidation.
Heart-type fatty acid-binding protein (H-FABP) is a major fatty acid-binding factor in skeletal muscles. Genetic lack of H-FABP severely impairs the esterification and oxidation of exogenous fatty acids in soleus muscles isolated from chow-fed mice (CHOW-solei) and high fat diet-fed mice (HFD-solei), and prevents the HFD-induced accumulation of muscle triacylglycerols (TAGs). Here, we examined the impact of H-FABP deficiency on the relationship between fatty acid utilization and glucose oxidation. Glucose oxidation was measured in isolated soleus muscles in the presence or absence of 1 mM palmitate (simple protocol) or in the absence of fatty acid after preincubation with 1 mM palmitate (complex protocol). With the simple protocol, the mutation slightly reduced glucose oxidation in CHOW-muscles, but markedly increased it in HFD-muscles; unexpectedly, this pattern was not altered by the addition of palmitate, which reduced glucose oxidation in both CHOW- and HFD-solei irrespective of the mutation. In the complex protocol, the mutation first inhibited the synthesis and accumulation of TAGs and then their mobilization; with this protocol, the mutation increased glucose oxidation in both CHOW- and HFD-solei. We conclude: (i) H-FABP mediates a non-acute inhibition of muscle glucose oxidation by fatty acids, likely by enabling both the accumulation and mobilization of a critical mass of muscle TAGs; (ii) H-FABP does not mediate the acute inhibitory effect of extracellular fatty acids on muscle glucose oxidation; (iii) H-FABP affects muscle glucose oxidation in opposing ways, with inhibition prevailing at high muscle TAG contents.
Adhikari
Sean
S
Department of Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, 1197 Raymond Stotzer Pkwy, College Station, TX 77843, USA.
Erol
Erdal
E
Binas
Bert
B
D000818:Animals; D004032:Diet; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism*; D010084:Oxidation-Reduction; D014280:Triglycerides / Q000378:metabolism*
C493409:Fabp3 protein, mouse; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D014280:Triglycerides; D006003:Glycogen; D005947:Glucose