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Optimized Analysis of In Vivo and In Vitro Hepatic Steatosis
Published on: March 11, 2017
Selective Inhibition of 11β-Hydroxysteroid Dehydrogenase Type 1 Attenuates High-Fat Diet-Induced Hepatic Steatosis in
Huashan Li1, Jianying Sheng1, Jing Wang1
1Jiangsu Key Laboratory of Neuropsychiatric Diseases and Cambridge-Suda (CAM-SU) Genomic Resource Center, Medical College of Soochow University, Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.
Introduction:
The effect of 11β-hydroxysteroid dehydrogenase type1 (11β-HSD1) inhibition on hepatic steatosis is incompletely understood. Here, we aimed to determine the therapeutic effect of BVT.2733, a selective 11β-HSD1 inhibitor, on hepatic steatosis.
Materials And Methods:
C57B/6J mice were randomly divided into a low-fat diet (LFD) fed group and a high-fat diet (HFD) fed group. Mice were fed with HFD for 28 weeks which induced obesity and severe hepatic steatosis. The two groups were further divided into four groups as follows: LFD, LFD with BVT.2733, HFD, and HFD with BVT.2733. Mice in LFD+BVT and HFD+BVT groups were intraperitoneally injected with BVT.2733 daily for 30 days. Effects of BVT.2733 on mice body weight, serum lipid profile, serum free fatty acids (FFAs), glucocorticoid levels, gene expression in adipose and liver tissues were assessed.
Results:
Injection of a low dose of BVT.2733 (50 mg/kg/day) reduced body weight and hyperlipidemia, but did not improve glucose tolerance and insulin resistance in diet-induced obese mice. The low dose of BVT.2733 attenuated hepatic steatosis, liver injury, and liver lipolytic gene expression in diet-induced obese mice. Besides, the low dose of BVT.2733 reduced fat mass and lipolysis in visceral adipose tissues, hepatic FFAs, and serum corticosterone levels in diet-induced obese mice.
Conclusion:
Our study shows that moderate inhibition of 11β-HSD1 by BVT.2733 reduces FFAs and corticosterone synthesis in fatty tissues, thereby attenuates the delivery of corticosterone and FFAs to the liver. Collectively, this prevents high-fat diet-induced hepatic steatosis.
Insights
Selective 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibition with BVT.2733 reduced hepatic steatosis in mice. This therapeutic effect was achieved by decreasing free fatty acids and corticosterone synthesis in fatty tissues.
Area of Science:
- Biochemistry
- Endocrinology
- Metabolic Diseases
Background:
- Hepatic steatosis pathogenesis is incompletely understood.
- 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) plays a role in metabolic regulation.
- Selective 11β-HSD1 inhibition is a potential therapeutic strategy for hepatic steatosis.
Purpose of the Study:
- To determine the therapeutic effect of BVT.2733, a selective 11β-HSD1 inhibitor, on diet-induced hepatic steatosis in mice.
- To investigate the impact of BVT.2733 on body weight, lipid profiles, and glucose metabolism.
- To assess the effects of BVT.2733 on gene expression in adipose and liver tissues.
Main Methods:
- C57B/6J mice were fed a high-fat diet (HFD) for 28 weeks to induce obesity and hepatic steatosis.
- Mice received daily intraperitoneal injections of BVT.2733 (50 mg/kg/day) or vehicle for 30 days.
- Evaluated body weight, serum lipid profiles, free fatty acids (FFAs), glucocorticoid levels, and tissue gene expression.
Main Results:
- BVT.2733 treatment reduced body weight, hyperlipidemia, hepatic steatosis, and liver injury in HFD-fed mice.
- The inhibitor decreased fat mass and lipolysis in visceral adipose tissue.
- BVT.2733 lowered hepatic FFAs and serum corticosterone levels, but did not improve glucose tolerance or insulin resistance.
Conclusions:
- Moderate 11β-HSD1 inhibition by BVT.2733 attenuates hepatic steatosis.
- The mechanism involves reduced FFAs and corticosterone synthesis in fatty tissues.
- This prevents the delivery of corticosterone and FFAs to the liver, mitigating HFD-induced hepatic steatosis.
