Accumulation of saturated intramyocellular lipid is associated with insulin resistance

J Lipid Res. 2019 Jul;60(7):1323-1332. doi: 10.1194/jlr.M091942. Epub 2019 May 2.

Abstract

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:CH3adj), could distinguish lipodystrophics from athletes. This CH2:CH3adj marker had a stronger relationship with insulin resistance than IMCL concentration alone and was inversely related to VO2max 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.

Keywords: exercise; fatty acids; in vivo; lipid composition; lipodystrophies; muscle; spectroscopy; triglycerides.

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Choline-Phosphate Cytidylyltransferase / genetics
  • Exercise / physiology
  • Fatty Acids / metabolism*
  • Female
  • Heart Rate / physiology
  • Humans
  • Insulin / metabolism
  • Insulin Resistance / genetics
  • Insulin Resistance / physiology*
  • Lamin Type A / genetics
  • Lipodystrophy / genetics
  • Lipodystrophy / metabolism
  • Magnetic Resonance Spectroscopy
  • Male
  • Muscle, Skeletal / metabolism*
  • Triglycerides / metabolism

Substances

  • Fatty Acids
  • Insulin
  • LMNA protein, human
  • Lamin Type A
  • Triglycerides
  • Choline-Phosphate Cytidylyltransferase
  • PCYT1A protein, human