Tao Yuan1, Juan Li1, Wei-Gang Zhao1, Yong Fu1, Shuai-Nan Liu2, Quan Liu3, Zhu-Fang Shen3. 1. Key Laboratory of Endocrinology,Ministry of Health,Department of Endocrinology,PUMC Hospital, CAMS and PUMC,Beijing 100730,China. 2. 2. State Key Laboratory of Bioactive Substances and Functions of Natural Medicines,Institute of Materia Medica, CAMS and PUMC,Beijing 100050,China. 3. State Key Laboratory of Bioactive Substances and Functions of Natural Medicines,Institute of Materia Medica, CAMS and PUMC,Beijing 100050,China.
Abstract
OBJECTIVE: To study the potential mechanisms via which estrogen exerts its effects on the insulin sensitivity in mice. METHODS: Totally 36 female C57BL/6J mice aged 6 weeks were randomly divided into six groups:normal diet (NOR) group, normal diet with ovariectomy (NOR+OVX) group, normal diet with ovariectomy and estrogen replacement (NOR+OVX+E2) group,high-fat diet (HF) group, high-fat diet with ovariectomy (HF+OVX) group, and high-fat diet with ovariectomy and estrogen replacement (HF+OVX+E2) group. There were six mice in each group. After the ovariectomy based on the grouping, the mice were given normal diet or high-fat diet for 20 weeks. The intervention groups were given estrogen (5 μg/d,subcutaneous injection) for 20 days. Then,the body weight,visceral fat weight,oral glucose tolerance and insulin sensitivity (by euglycemic hyperinsulinemic clamp test), and serum leptin, adiponectin,and resistin levels were compared among these six groups. RESULTS: Compared with HF group, the HF+OVX group had significantly higher body weight and visceral fat weight and lower glucose tolerance, which were significantly improved after estrogen replacement therapy (all P<0.05). However, these indicators showed no significant differences among groups with normal diets (all P>0.05). The insulin sensitivity of ovariectomized mice was significantly decreased in both high-fat and normal diet groups and was also improved significantly after estrogen replacement (P<0.05). The serum leptin was increased and adiponectin was decreased significantly in ovariectomized mice, and the improvements of these two adipokines were also statistically significant after estrogen therapy (P<0.05): however,the serum resistin level was not significantly different among these 6 groups (P>0.05). CONCLUSIONS: Estrogen replacement therapy can improve insulin resistance by lowering body weight. In addition, it can exert its effect directly on adipose tissue,improve the levels of adipokines,reduce the amount of visceral fat, and improve insulin sensitivity in mice.
OBJECTIVE: To study the potential mechanisms via which estrogen exerts its effects on the insulin sensitivity in mice. METHODS: Totally 36 female C57BL/6J mice aged 6 weeks were randomly divided into six groups:normal diet (NOR) group, normal diet with ovariectomy (NOR+OVX) group, normal diet with ovariectomy and estrogen replacement (NOR+OVX+E2) group,high-fat diet (HF) group, high-fat diet with ovariectomy (HF+OVX) group, and high-fat diet with ovariectomy and estrogen replacement (HF+OVX+E2) group. There were six mice in each group. After the ovariectomy based on the grouping, the mice were given normal diet or high-fat diet for 20 weeks. The intervention groups were given estrogen (5 μg/d,subcutaneous injection) for 20 days. Then,the body weight,visceral fat weight,oral glucose tolerance and insulin sensitivity (by euglycemic hyperinsulinemic clamp test), and serum leptin, adiponectin,and resistin levels were compared among these six groups. RESULTS: Compared with HF group, the HF+OVX group had significantly higher body weight and visceral fat weight and lower glucose tolerance, which were significantly improved after estrogen replacement therapy (all P<0.05). However, these indicators showed no significant differences among groups with normal diets (all P>0.05). The insulin sensitivity of ovariectomized mice was significantly decreased in both high-fat and normal diet groups and was also improved significantly after estrogen replacement (P<0.05). The serum leptin was increased and adiponectin was decreased significantly in ovariectomized mice, and the improvements of these two adipokines were also statistically significant after estrogen therapy (P<0.05): however,the serum resistin level was not significantly different among these 6 groups (P>0.05). CONCLUSIONS: Estrogen replacement therapy can improve insulin resistance by lowering body weight. In addition, it can exert its effect directly on adipose tissue,improve the levels of adipokines,reduce the amount of visceral fat, and improve insulin sensitivity in mice.
Authors: Sebastian I Arriola Apelo; Amy Lin; Jacqueline A Brinkman; Emma Meyer; Mark Morrison; Jay L Tomasiewicz; Cassidy P Pumper; Emma L Baar; Nicole E Richardson; Mohammed Alotaibi; Dudley W Lamming Journal: Elife Date: 2020-07-28 Impact factor: 8.140
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