Intramyocellular lipid levels are associated with peripheral, but not hepatic, insulin sensitivity in normal healthy subjects

Abstract

A B S T R A C T Increased levels of IMCL (intramyocellular lipid) have been shown to be associated with reduced steady-state glucose infusion rates during a hyperinsulinaemic-euglycaemic clamp (M-value). The aim of the present study was to explore how IMCL levels relate to the insulin-mediated suppression of endogenous glucose production [hepatic S I (insulin sensitivity)] and increase in glucose disposal (peripheral S I ). In the present study, 11 healthy young adults (7 male, 4 female; aged 21-31 years) undertook, in random order, an hyperinsulinaemic-euglycaemic clamp combined with stable glucose isotope enrichment to measure peripheral and hepatic S I , a 1 H-MRS (protonmagnetic resonance spectroscopy) scan to determine IMCL levels and a DXA (dual-energy X-ray absorptiometry) scan to assess body composition. IMCL levels (range, 3.2-10.7) were associated with whole-body fat mass (r = 0.787, P = 0.004), fat mass corrected for height (r = 0.822, P = 0.002) and percentage of central fat mass (r = 0.694, P = 0.02), but were not related to whole-body FFM (fat-free mass; r = − 0.472, P = 0.1). IMCL levels correlated closely with the M-value (r = − 0.727, P = 0.01) and FFM-corrected peripheral S I (r = − 0.675, P = 0.02), but were not related to hepatic S I adjusted for body weight (r = 0.08, P = 0.8). The results of the present study suggest that IMCL accumulation may be a sensitive marker for attenuations in peripheral, but not hepatic, S I in normal populations. Given the close relationship of IMCL levels to whole-body and central abdominal fat mass, relative increases in the flux of lipids from adipose tissue to the intramyocellular compartment may be an integral part of the mechanisms underlying reductions in S I