Abstract
The lower incidence of metabolic diseases of women than men and the increasing morbidity of metabolic disorders of menopausal women indicated that hormones produced by ovaries may affect homeostasis of glucose and lipid metabolism, but the underlying mechanisms remain unclear. To explore the functions of ovaries on regulating glucose and lipid metabolism in females, 8 weeks old C57BL/6 mice were preformed ovariectomy and administrated with normal food diet (NFD) or high fat diet (HFD). Six weeks after ovariectomy, blood biochemical indexes were tested and the morphology and histology of livers were checked. The expression levels of genes related to glucose and lipid metabolism in liver were detected through transcriptome analysis, qPCR and western blot assays. 16S rDNA sequence was conducted to analyze the gut microbiota of mice with ovariectomy and different diets. The serum total cholesterol (TC) was significantly increased in ovariectomized (OVX) mice fed with NFD (OVXN), and serum low density lipoprotein-cholesterol (LDL-C) was significantly increased in both OVXN mice and OVX mice fed with HFD (OVXH). The excessive glycogen storage was found in livers of 37.5% mice from OVXN group, and lipid accumulation was detected in livers of the other 62.5% OVXN mice. The OVXN group was further divided into OVXN-Gly and OVXN-TG subgroups depending on histological results of the liver. Lipid drops in livers of OVXH mice were more and larger than other groups. The expression level of genes related with lipogenesis was significantly increased and the expression level of genes related with β-oxidation was significantly downregulated in the liver of OVXN mice. Ovariectomy also caused the dysbiosis of intestinal flora of OVXN and OVXH mice. These results demonstrated that hormones generated by ovaries played important roles in regulating hepatic glucose and lipid metabolism and communicating with the gut microbiota in females.
Highlights
The prevalence of glucose and lipid metabolic disorders is increasing worldwide [1, 2] and metabolic diseases are more prevalent in men than in age-matched women [3,4,5]
The concentration of serum LDLC in the SH group was significantly higher than that of SN group, the total cholesterol (TC) concentration in the serum was no significant difference between these two groups (Figure 1D); and the low density lipoprotein-cholesterol (LDL-C) concentration in the serum of OVX mice fed with HFD (OVXH) group was significantly increased compared with the OVXN group (Figure 1D)
The concentration of ALT and AST in the serum of ovariectomized mice was not affected (Figures S1D, E). These results demonstrated that both ovariectomy and high fat diet (HFD) could induce the increase of the serum LDL-C in females, the increase of the body weight of female mice was only caused by ovariectomy within six weeks after operation
Summary
The prevalence of glucose and lipid metabolic disorders is increasing worldwide [1, 2] and metabolic diseases are more prevalent in men than in age-matched women [3,4,5]. Several studies have confirmed that estrogen deficiency would increase metabolic dysfunctions, including obesity, type 2 diabetes and the metabolic syndrome, even certain cancers [9,10,11]. It has been confirmed that menopause was one of risk factors for glucose and lipid metabolic disorders, including type 2 diabetes, metabolic syndrome and CDV [15]. Kim et al [21] reported the obesity and nonalcoholic fatty liver disease (NALFD) phenotype in ovariectomized female mice. These studies indicated that ovaries had important functions in maintaining the homeostasis of glucose and lipid metabolism, and it would be very meaningful to elucidate the molecular mechanisms of ovaries on regulating metabolism in females
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