Amelioration of hepatic steatosis is associated with modulation of gut microbiota and suppression of hepatic miR-34a in Gynostemma pentaphylla (Thunb.) Makino treated mice

Ning Jia; Xiaoyan Lin; Shizhan Ma; Shujian Ge; Shumin Mu; Chongbo Yang; Shulong Shi; Ling Gao; Jin Xu; Tao Bo; Jiajun Zhao

doi:10.1186/s12986-018-0323-6

Amelioration of hepatic steatosis is associated with modulation of gut microbiota and suppression of hepatic miR-34a in Gynostemma pentaphylla (Thunb.) Makino treated mice

Nutr Metab (Lond). 2018 Dec 5:15:86. doi: 10.1186/s12986-018-0323-6. eCollection 2018.

Authors

Ning Jia^{1

2

3

4}, Xiaoyan Lin⁵, Shizhan Ma^{2

3

4}, Shujian Ge⁶, Shumin Mu⁷, Chongbo Yang^{2

3

4}, Shulong Shi^{1

2

3

4}, Ling Gao^{3

4

8}, Jin Xu^{2

3

4}, Tao Bo⁸, Jiajun Zhao^{1

2

3

4}

Affiliations

¹ 1Shandong University of Traditional Chinese Medicine, Jinan, 250355 China.
² 2Department of Endocrinology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, 250021 China.
³ Shandong Provincial Key Laboratory of Institute of Endocrinology and Lipid Metabolism, Jinan, 250021 China.
⁴ Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, 250021 China.
⁵ 6Department of Pathology, Shandong Provincial Hospital affiliated to Shandong University, 324, Jing 5 Rd, Jinan, 250021 China.
⁶ 7Department of Scientific Research, Shandong Provincial Hospital affiliated to Shandong University, 324, Jing 5 Rd, Jinan, 250021 China.
⁷ 8Department of Endocrinology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250014 China.
⁸ 5Scientific Center, Shandong Provincial Hospital affiliated to Shandong University, 324, Jing 5 Rd, Jinan, 250021 China.

Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) is a chronic and progressive liver disease with an increased risk of morbidity and mortality. However, so far no specific pharmacotherapy has been approved. Gynostemma pentaphylla (Thunb.) Makino (GP) is a traditional Chinese medicine that is widely used against hyperlipemia as well as hyperglycemia. This study aims to evaluate the effect of GP on NAFLD and explore the possible mechanism.

Methods: High-fat-diet induced NAFLD mice model were orally administrated with GP at dose of 11.7 g/kg or equivalent volume of distilled water once a day for 16 weeks. Body weight, food intake and energy expenditure were assessed to evaluate the general condition of mice. The triglycerides, total cholesterol content in the liver and liver histopathology, serum lipid profile and serum insulin level, fecal microbiome, hepatic microRNAs and relative target genes were analyzed.

Results: Mice in GP treatment group displayed improved hepatic triglycerides content with lower lipid droplet in hepatocyte and NAFLD activity score. Besides, GP treatment altered the composition of gut microbiota and the relative abundance of some of the key components that are implicated in metabolic disorders, especially phylum Firmicutes (Eubacterium, Blautia, Clostridium and Lactobacillus). Several hepatic microRNAs were downregulated by GP treatment such as miR-130a, miR-34a, miR-29a, miR-199a, among which the expression miR-34a was altered by more than four-fold compared to that of HFD group (3:14). The correlation analysis showed that miR-34a was strongly related to the change of gut microbiota especially phylum Firmicutes (R = 0.796). Additionally, the target genes of miR-34a (HNF4α, PPARα and PPARα) were restored by GP both in mRNA and protein levels.

Conclusion: Our results suggested that GP modulated the gut microbiota and suppressed hepatic miR-34a, which was associated with the amelioration of hepatic steatosis.

Keywords: Gut microbiota; Gynostemma pentaphylla (Thunb.) Makino; Lipid metabolism; Non-alcoholic fatty liver disease; miR-34a.