Accumulation of saturated intramyocellular lipid is associated with insulin resistance

Intramyocellular lipid (IMCL) accumulation has been linked to both insulin-resistant and insulin-sensitive (athletes) states. Biochemical analysis of intramuscular triglyceride composition is confounded by extramyocellular triglycerides in biopsy samples, and hence the specific composition of IMCLs is unknown in these states. ¹H magnetic resonance spectroscopy (MRS) can be used to overcome this problem. Thus, we used a recently validated ¹H MRS method to compare the compositional saturation index (CH₂:CH₃) and concentration independent of the composition (CH₃) of IMCLs in the soleus and tibialis anterior muscles of 16 female insulin-resistant lipodystrophic subjects with that of age- and gender-matched athletes (n = 14) and healthy controls (n = 41). The IMCL CH₂:CH₃ ratio was significantly higher in both muscles of the lipodystrophic subjects compared with controls but was similar in athletes and controls. IMCL CH₂:CH₃ was dependent on the IMCL concentration in the controls and, after adjusting the compositional index for quantity (CH₂:CH_3adj), could distinguish lipodystrophics from athletes. This CH₂:CH_3adj marker had a stronger relationship with insulin resistance than IMCL concentration alone and was inversely related to VO_2max The association of insulin resistance with the accumulation of saturated IMCLs is consistent with a potential pathogenic role for saturated fat and the reported benefits of exercise and diet in insulin-resistant states.