Fatty acid transport proteins chronically relocate to the transverse-tubules in muscle from obese Zucker rats but are resistant to further insulin-induced translocation.

Objectives: Recently, we have demonstrated that FA transport proteins are located within the t-tubule fraction of rodent muscle, and that insulin stimulation causes their translocation to this membrane fraction. Chronic relocation of the FA transport protein FAT/CD36 to the sarcolemma is observed in obese rodents and humans, and correlates with intramuscular lipid accumulation and insulin resistance. It is not known whether in an obese, insulin resistant state FA transporters also chronically relocate to the t-tubules. Furthermore, it is not known whether the insulin-stimulated translocation of the various FA transport proteins to the t-tubules is impaired in insulin resistance.

Methods: Sarcolemmal and t-tubule membrane fractions were isolated via differential centrifugation from muscles of lean and obese female Zucker rats during basal or insulin stimulated conditions. FA transport proteins were measured via western blot on both membrane fractions.

Results: Our results demonstrate that in muscle from insulin resistant Zucker rats, FAT/CD36, FABPpm and FATP1 are all increased on the t-tubules in the basal state (+72%, +120%, and +69%, respectively), potentially contributing to the accumulation of intramuscular lipids. Insulin failed to increase the content of the FA transport proteins on either the t-tubule or sarcolemma above the elevated basal levels, analogous to the well characterized impairment of insulin-stimulated GLUT4 translocation to both membrane domains in obesity.

Conclusion: FA transport proteins chronically relocate to the t-tubule domain in insulin resistant muscle, potentially contributing to lipid accumulation. Further translocation of the FA transport proteins to this domain during insulin stimulation, however, is impaired.