Liver-specific G0/G1switch gene 2 (G0s2) expression promotes hepatic insulin resistance by exacerbating hepatic steatosis in male Wistar rats.
BACKGROUND
Hepatic steatosis is strongly associated with insulin resistance. It has been reported that G0/G1switch gene 2 (G0s2) inhibits the lipolytic activity of adipose triglyceride lipase, which is a major lipase in the liver as well as in adipocytes. Moreover, G0s2 protein content is increased in the livers of high-fat diet (HFD)-fed rats. In the present study, we investigated the effect of hepatic G0s2 on insulin sensitivity in male Wistar rats.


METHODS
Male Wistar rats were fed a 60% HFD for 4 weeks. After 3 weeks of feeding, rats were injected with adenovirus-expressing green fluorescent protein (Ad-GFP; control) or adenovirus-expressing mouse G0s2 (Ad-G0s2). On Day 7 after injection, a euglycemic-hyperinsulinemic clamp study was performed in rats fasted for 8 h.


RESULTS
Body weight and fasting glucose levels were not significantly different between the Ad-GFP and Ad-G0s2 groups. During the clamp study, the glucose infusion rate required for euglycemia decreased significantly by 16% in the Ad-G0s2 compared with Ad-GFP group. The insulin-suppressed hepatic glucose output increased significantly in the Ad-G0s2 group, but the insulin-stimulated glucose disposal rate was not significantly different between the two groups. Consistent with the clamp data, insulin-stimulated phosphorylation of Akt decreased significantly in livers of rats injected with Ad-G0s2. Furthermore, Oil Red O-staining indicated that overexpression of G0s2 protein in the liver promoted hepatic steatosis by 2.5-fold in HFD-fed rats.


CONCLUSIONS
The results of the present study indicate that hepatic G0s2 protein may promote hepatic insulin resistance by exacerbating hepatic steatosis.
Department of Nephrology, Hypertension, Diabetology, Endocrinology, and Metabolism, Fukushima Medical University, Fukushima, Japan.
Yoshiyuki
Y
Sugaya
Department of Nephrology, Hypertension, Diabetology, Endocrinology, and Metabolism, Fukushima Medical University, Fukushima, Japan.
Hiroaki
H
Satoh
D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics*; D059305:Diet, High-Fat; D005234:Fatty Liver / Q000235:genetics / Q000473:pathology*; D005951:Glucose Tolerance Test; D057809:HEK293 Cells; D006801:Humans; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D018797:Cell Cycle Proteins; C508073:G0S2 protein, human
G0/G1 switch gene 2 (G0s2); G0/G1开关基因2(G0s2); hepatic insulin resistance; hepatic steatosis; 肝脏胰岛素抵抗; 肝脏脂肪变性