Effect of obeticholic acid on glucolipid homeostasis in high-fat fed C57BL/6J mice

doi:10.16352/j.issn.1001-6325.2023.05.0755

Abstract

Abstract: Objective To investigate the effects of obeticholic acid (OCA) on glucolipid metabolism in high-fat fed C57BL/6J mice. Methods After 12 weeks of high-fat diet (HFD) feeding, C57BL/6J mice were randomly divided into two groups: model group (model) and OCA intervention group (10 mg/kg, gavage for six weeks), with 10 in each. The C57BL/6J mice were fed with normal diet for 12 weeks as the control group. The model group and the control group were given 0.5% sodium carboxymethyl cellulose (CMC-Na) by gavage. During the experiment, oral glucose and insulin tolerance tests were conducted. At the end of the experiment, the liver function related indicators were measured in serum, and the liver weight was recorded. The lipid-related indicators were measured in liver, and HE staining microscopy was performed. RT-qPCR was used to detected the expression of genes related to lipid metabolism in liver. Results After glucose loading and insulin injection, the blood glucose at each time point and area under curve (AUC) of the model group were significantly higher than those of the control group (P＜0.01). Abnormal glucose tolerance in OCA intervention group was reversed(P＜0.05) and the insulin sensitivity of the model group mice was improved(P＜0.05). The serum level of triglyceride (TG), total cholesterol (TC), free fatty acid (FFA), low density lipoprotein total cholesterol (LDL-C), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the model group was all significantly higher than those in the control group (P＜0.01), and HDL-C level was evidently lower than that in the control group (P＜0.01). The OCA intervention group could significantly reduce the serum levels of TG, TC, FFA, LDL-C, ALT, AST (P＜0.01) and increase the serum HDL-C content in the model group (P＜0.01). The contents of TG, TC, and FFA in the liver of the model group were significantly higher than those in the control group (P＜0.01), and OCA intervention group did alleviate the hepatic steatosis in the model group (P＜0.05). Compared with the control group, the expression of FXR/SREBP pathway related genes in model group was abnormal (P＜0.01), and OCA intervention reversed abnormal expression of FXR/SREBP pathway related genes in model group (P＜0.05). Conclusions OCA may improve the lipid metabolism disorder in the liver of HFD mice by regulating the FXR/SREBP pathway, thus improve the impaired glucose tolerance and insulin resistance in HFD mice.

Key words: obeticholic acid, high-fat diet, C57BL/6J mice, glycolipid metabolism, hepatic steatosis

CLC Number:

R965

WANG Xing, GUO Nan. Effect of obeticholic acid on glucolipid homeostasis in high-fat fed C57BL/6J mice[J]. Basic & Clinical Medicine, 2023, 43(5): 755-761.

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URL: http://journal11.magtechjournal.com/Jwk_jcyxylc/EN/10.16352/j.issn.1001-6325.2023.05.0755

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