Abstract

The gut microbiota plays a critical role in obesity and lipid metabolism disorder. Chokeberry (Aronia melanocarpa L.) are rich in polyphenols with various physiological and pharmacological activities. We determined serum physiological parameters and fecal microbial components by using related kits, liquid chromatography-mass spectrometry (LC-MS) and 16S rRNA gene sequencing every 10 days. Real-time PCR analysis was used to measure gene expression of bile acids (BAs) and lipid metabolism in liver and adipose tissues. We analyzed the effects of different Chokeberry polyphenol (CBPs) treatment time on obesity and lipid metabolism in high fat diet (HFD)-fed rats. The results indicated that CBPs treatment prevents obesity, liver steatosis and improves dyslipidemia in HFD-fed rats. CBPs modulated the composition of the gut microbiota with the extended treatment time, reducing the Firmicutes/Bacteroidetes ratio (F/B ratio) and increasing the relative abundance of Bacteroides, Prevotella, Akkermansia and other bacterial species associated with anti-obesity properties. We found that CBPs treatment gradually decreased the total BAs pool and particularly reduced the relative content of cholic acid (CA), deoxycholic acid (DCA) and enhanced the relative content of chenodeoxycholic acid (CDCA). These changes were positively correlated Bacteroides, Prevotella and negatively correlated with Clostridium, Eubacterium, Ruminococcaceae. In liver and white adipose tissues, the gene expression of lipogenesis, lipolysis and BAs metabolism were regulated after CBPs treatment in HFD-fed rats, which was most likely mediated through FXR and TGR-5 signaling pathway to improve lipid metabolism. In addition, the mRNA expression of PPARγ, UCP1 and PGC-1α were upregulated markedly in interscapular brown adipose tissue (iBAT) after CBPs treatment. We confirmed that CBPs could reduce the body weight of HFD-fed rats by accelerating energy homeostasis and thermogenesis in iBAT. Finally, the fecal microbiota transplantation (FMT) experiment results demonstrated that FMT from CBPs-treated rats failed to reduce the weight of HFD-fed rats. However, FMT from CBPs-treated rats improved dyslipidemia and reshaped gut microbiota in HFD-fed rats. In conclusion, CBPs treatment improved obesity and complications by regulating gut microbiota in HFD-fed rats. The gut microbiota plays an important role in BAs metabolism after CBPs treatment, and BAs have therefore emerged as major effectors in microbe-host signaling events that influence host lipid metabolism, energy metabolism and thermogenesis.

Highlights

  • Obesity, a state of chronic subclinical inflammation, is the key element associated with the development of various metabolic disorders [1, 2]

  • Lipid metabolism disorders is intimately present in obesity, which are accompanied by symptoms of dyslipidemia that include exceeding serum levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), and lower level of high density lipoprotein cholesterol (HDL-C)

  • This study revealed that dietary supplementation of Chokeberry polyphenol (CBPs) regulates the mRNA expression related to lipogenesis, lipolysis, energy homeostasis and thermogenesis in liver and adipose tissues, which was most likely mediated through FXR and TGR-5 signaling pathway to improve lipid metabolism

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Summary

Introduction

A state of chronic subclinical inflammation, is the key element associated with the development of various metabolic disorders [1, 2]. Lipid metabolism disorders is intimately present in obesity, which are accompanied by symptoms of dyslipidemia that include exceeding serum levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), and lower level of high density lipoprotein cholesterol (HDL-C). These symptoms are induced by the dysregulation of hepatic lipid metabolism [3, 4]. Statins therapy is associated with some adverse effects including myotoxicity, diabetes mellitus, central nervous system complaints and hepatotoxicity [8, 9], which limits effectiveness in the treatment of patients with cardiovascular diseases

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