Ectopic Fat Accumulation and Distant Organ-Specific Insulin Resistance in Japanese People with Nonalcoholic Fatty Liver Disease

ObjectiveThe aim of this study was to examine the association between ectopic fat and organ-specific insulin resistance (IR) in insulin-target organs in patients with nonalcoholic fatty liver disease (NAFLD).MethodsOrgan-specific IR in the liver (hepatic glucose production (HGP)×fasting plasma insulin (FPI) and suppression of HGP by insulin [%HGP]), skeletal muscle (insulin-stimulated glucose disposal [Rd]), and adipose tissue (suppression of FFA by insulin [%FFA]) was measured in 69 patients with NAFLD using a euglycemic hyperinsulinemic clamp with tracer infusion ([6,6-2H2]glucose). Liver fat, intramyocellular lipid (IMCL), and body composition were measured by liver biopsy, proton magnetic resonance spectroscopy, and bioelectrical impedance analysis, respectively.ResultsHGP×FPI was significantly correlated with Rd (r = −0.57, Pr = 0.38, Pr = 0.27, Pr = −0.47, Pr = 0.43, Pr = −0.32, Pr = −0.16, P = 0.26). Fat mass and its percentage were associated with HGP×FPI (r = 0.50, Pr = 0.48, Pr = −0.59, Pr = −0.52, Pr = −0.21, P = 0.10; r = −0.001, P = 0.99, respectively).ConclusionUnexpectedly, fat accumulation in the skeletal muscle and adipose tissue was not associated with organ-specific IR. Instead, liver fat was associated not only with hepatic IR but also with skeletal muscle IR, suggesting a central role of fatty liver in systemic IR and that a network exists between liver and skeletal muscle.