Yoshiyuki Sugaya1, Hiroaki Satoh1. 1. Department of Nephrology, Hypertension, Diabetology, Endocrinology, and Metabolism, Fukushima Medical University, Fukushima, Japan.
Abstract
BACKGROUND: Hepatic steatosis is strongly associated with insulin resistance. It has been reported that G0 /G1 switch 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. CONCLUSION: The results of the present study indicate that hepatic G0s2 protein may promote hepatic insulin resistance by exacerbating hepatic steatosis.
BACKGROUND:Hepatic steatosis is strongly associated with insulin resistance. It has been reported that G0 /G1 switch 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 mouseG0s2 (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. CONCLUSION: The results of the present study indicate that hepatic G0s2 protein may promote hepatic insulin resistance by exacerbating hepatic steatosis.
Authors: Pedro Sousa-Victor; Joana Neves; Wendy Cedron-Craft; P Britten Ventura; Chen-Yu Liao; Rebeccah R Riley; Ilya Soifer; Nicholas van Bruggen; Ganesh A Kolumam; Saul A Villeda; Deepak A Lamba; Heinrich Jasper Journal: Nat Metab Date: 2019-01-14