Abstract:

Objective To investigate the effects of ovariectomy on the blood glucose， adipose tissue content and liver lipid deposition in the normal or hyperinsulinemia mice. Methods Twenty 6-week-old female loss of skeletal muscle-specific insulin-like growth factor-1 receptor function（MKR） hyperinsulinemia mice were randomly divided into MKR sham operation group （MKR group） and MKR ovariectomy group （MKR OVX group），with 10 mice in each group；twenty wild-type （WT） FVB/N mice were randomly divided into WT sham operation group（WT group） and WT ovariectomy group（WT OVX group），with 10 mice in each group. After two weeks of recovery feeding， the body weights and blood glucose levels of the mice in various groups were monitored. Glucose tolerance abilities and insulin sensitivities of the mice in various groups were detected by glucose tolerance test（GTT） and insulin tolerance test（ITT）. The mice were sacrificed 12 weeks after surgery，and the weights of liver and adipose of the mice in various groups were weighed.The pathomorphology of liver and gonadal adipose tissue of the mice in various groups were observed by HE staining，glycogen staining and oil red O staining. The expression levels of lipid metabolization-related gene mRNA in gonadal adipose tissue of the mice in various groups were detected by real-time fluorescence quantitative PCR（RT-qPCR） method. Western blotting method was used to detect the expression levels of hormone sensitive lipase（HSL） in gonadal adipose tissue of the mice in various groups. Results The body weight of the mice in MKR group was significantly decreased compared with WT group （P<0.05）； compared with MKR group， the body weight of the mice in MKR OVX group was significantly increased （P<0.05）， but compared with WT and WT OVX groups，the body weight of the mice in MKR OVX group was decreased （P<0.05）. In MKR OVX group， the blood glucose of the mice was gradually increased， and severe glucose intolerance and insulin resistance appeared. Compared with WT group， liver steatosis was found and glycogen was decreased in WT OVX group （P<0.05）， while the liver steatosis degree was increased and glycogen was decreased significantly in MKR OVX group.Compared with WT group，the gonadal adipose index and mesenteric adipose index of the mice in WT OVX group were increased（P<0.05）；compared with MKR group，the gonadal adipose index and perirenal adipose index of the mice in MKR OVX group was increased（P<0.05）.The HE staining results showed that the adipocytes in MKR group were significantly shunk compared with WT group， and the adipocytes were enlarged in WT OVX group and MKR OVX group，the adipocytes in MKR OVX group were still shunk compared with WT group and WT OVX group. Compared with WT group， the expression levels of HSL mRNA and protein in gonadal adipose tissue of the mice in MKR group were increased （P<0.05）， while the expression levels of HSL mRNA and protein in gonadal adipose tissue of the mice in WT OVX group and MKR OVX group were decreased（P<0.05）. Conclusion Ovariectomy can lead to dysglycemia， adipose tissue mass increasing and lipid deposition in the liver in the mice. High endogenous insulin levels and insulin resistance can further aggravate the dysglycemia caused by ovariectomy.

Key words: Hyperinsulinemia, Ovariectomy, Loss of skeletal muscle-specific insulin-like growth factor-1 receptor function mice, Glucose and lipid metabolism