Ectopic fat accumulation and distant organ-specific insulin resistance in Japanese people with nonalcoholic fatty liver disease.

Abstract

OBJECTIVE:

The 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).

METHODS:

Organ-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.

RESULTS:

HGP × FPI was significantly correlated with Rd (r =  -0.57, P<0.001), %HGP with %FFA (r = 0.38, P<0.01), and Rd with %FFA (r = 0.27, P<0.05). Liver steatosis score was negatively associated with Rd (r =  -0.47, P<0.001) as well as with HGP × FPI (r = 0.43, P<0.001). Similarly, intrahepatic lipid was negatively associated with Rd (r =  -0.32, P<0.05). IMCL was not associated with Rd (r =  -0.16, P = 0.26). Fat mass and its percentage were associated with HGP × FPI (r = 0.50, P<0.001; r = 0.48, P<0.001, respectively) and Rd (r =  -0.59, P<0.001; r =  -0.52, P<0.001, respectively), but not with %FFA (r =  -0.21, P = 0.10; r =  -0.001, P = 0.99, respectively).

CONCLUSION:

Unexpectedly, 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.

• Authors: Ken-ichiro Kato, Toshinari Takamura, Yumie Takeshita, Yasuji Ryu, Hirofumi Misu, Tsuguhito Ota, Kumpei Tokuyama, Shoichiro Nagasaka, Munehide Matsuhisa, Osamu Matsui, Shuichi Kaneko
• Journal: PloS one (PLoS One) Vol. 9 Issue 3 Pg. e92170 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 24651470 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Insulin
• Glucose

Topics

• Adiposity
• Asian People
• Diabetes Mellitus, Type 2 (blood, complications)
• Fasting (blood)
• Female
• Glucose (biosynthesis)
• Humans
• Insulin (blood)
• Insulin Resistance
• Japan
• Liver (metabolism, pathology)
• Male
• Middle Aged
• Non-alcoholic Fatty Liver Disease (blood, complications, pathology)
• Organ Specificity
• Regression Analysis