Hemin prevents insulin resistance in skeletal muscle not in liver in high fat-fed mice

Presentation Number: MON-850
Date of Presentation: June 17th, 2013

So-Young Park*1, Tae-Jin Ju2, Yong-woon Kim2, Kyu Chang Won3, Jong-yeon Kim2 and Hyo-Jeong Kim4
1College of Medicine, Yeungnam Un, Namgu, Daegu, Korea, Republic of (South), 2College of Medicine, Yeungnam University, 3Yeungnam Univ Hosp, Daegu, Korea, Republic of (South), 4School of Medicine, Eulji University, Seoul, Korea, Republic of (South)

Abstract

HO-1 inducer hemin is known to suppress insulin resistance. However, it is not known whether hemin prevents high fat diet-induced insulin resistance. In this study, we examined whether hemin prevents insulin resistance in high fat-fed mice using hyperinsulinemic-euglycemic clamp study. Mice were divided into Chow diet (CD), CD+Hemin (CDH), High-fat diet (HFD) and HFD+hemin (HFDH). High-fat diet was fed for 4 weeks and hemin in dimethylsulfoxide (DMSO) was injected intraperitoneally (50 μmol/kg) every day during high-fat feeding. Body weight and fat mass were increased after 4-week high fat feeding in HFD. However, hemin injection abrogated increase in body weight and fat mass by high fat diet. Food intake was not different between HFD and HFDH. Although plasma fatty acid and triglycerides levels were increased by high fat diet both in HFD and HFDH compared with CD, they were significantly lower in HFDH compared with HFD. High-fat diet decreased glucose infusion rate (GIR) and whole body glucose uptake in HFD, whereas it did not decreased GIR and whole body glucose uptake in HFDH compared with CD. Moreover, GIR and whole body glucose uptake in HFDH were significantly higher than those in HFD. High-fat diet decreased skeletal muscle glucose uptake in HFD compared with CD. However, skeletal muscle glucose uptake in HFDH was not decreased. Basal hepatic glucose production (HGP) was not different among the groups. High fat feeding increased insulin-stimulated HGP both in HFD and HFDH compared with CD and there was no difference between two groups. While skeletal muscle triglyceride levels were increased in HFD compared with CD, it was not increased in HFDH. Gene expression of antioxidant enzymes were reduced in the skeletal muscle of HFD, which was partially suppressed in HFDH. Gene expression of cytokines in skeletal muscle was increased in HFD and hemin injection suppressed the increment. Liver triglyceride levels were increased in HFD and hemin had no effect on triglyceride level. Altered gene expression of cytokines and antioxidants enzymes in HFD was not reversed by hemin injection in liver. These results suggest that hemin has a protective effect on skeletal muscle insulin resistance by high fat diet but has no effect on liver .

 

Nothing to Disclose: SYP, TJJ, YWK, KCW, JYK, HJK