CST, an Herbal Formula, Exerts Anti-Obesity Effects through Brain-Gut-Adipose Tissue Axis Modulation in High-Fat Diet Fed Mice.

Abuzar Ansari,Seong-Gyu Ko,Jing-Hua Wang,Shambhunath Bose,Yun-Kyung Song,Hojun Kim,Mukesh Kumar Yadav

doi:10.3390/molecules21111522

Abstract

The brain, gut, and adipose tissue interact to control metabolic pathways, and impairment in the brain-gut-adipose axis can lead to metabolic disorders, including obesity. Chowiseungcheng-tang (CST), a herbal formulation, is frequently used to treat metabolic disorders. Here, we investigated the anti-obesity effect of CST and its link with brain-gut-adipose axis using C57BL/6J mice as a model. The animals were provided with a normal research diet (NRD) or high-fat diet (HFD) in absence or presence of CST or orlistat (ORL) for 12 weeks. CST had a significant anti-obesity effect on a number of vital metabolic and obesity-related parameters in HFD-fed mice. CST significantly decreased the expression levels of genes encoding obesity-promoting neuropeptides (agouti-related peptide, neuropeptide Y), and increased the mRNA levels of obesity-suppressing neuropeptides (proopiomelanocortin, cocaine-and amphetamine-regulated transcript) in the hypothalamus. CST also effectively decreased the expression level of gene encoding obesity-promoting adipokine (retinol-binding protein-4) and increased the mRNA level of obesity-suppressing adipokine (adiponectin) in visceral adipose tissue (VAT). Additionally, CST altered the gut microbial composition in HFD groups, a phenomenon strongly associated with key metabolic parameters, neuropeptides, and adipokines. Our findings reveal that the anti-obesity impact of CST is mediated through modulation of metabolism-related neuropeptides, adipokines, and gut microbial composition.

Highlights

Obesity is a major global public health problem, closely associated with the onset and development of other diseases and disorders such as chronic inflammation, type 2 diabetes, insulin resistance, cardiovascular disease, neurodegenerative disorder, cancer as well as aging [1]
Very few studies have been carried out to understand the mechanisms of action of herbal medicines against obesity
The function of this axis is regulated by the interaction among neuropeptides, adipokines, and gut microbiota

Summary

Introduction

Obesity is a major global public health problem, closely associated with the onset and development of other diseases and disorders such as chronic inflammation, type 2 diabetes, insulin resistance, cardiovascular disease, neurodegenerative disorder, cancer as well as aging [1]. Genetic and epigenetic factors are major determinants of obesity [3], accumulating evidence indicates that the gut microbiota vital in energy homeostasis significantly influence obesity and the related metabolic disorders [4]. The inter-organ communication among the brain, gut, and adipose tissue, collectively termed the ‘brain-gut-adipose tissue axis’ is hypothesized as crucial in controlling several metabolic functions [6,7]. Inter-organ communication is significantly disordered, which contributes to the changes in energy intake and energy expenditure, facilitates lipid deposition, and induces insulin resistance. Brain-derived neuropeptides influence the bidirectional communication between the components of brain-gut axis [8], while adipocyte-derived adipokines are integrally involved in energy homeostasis, neuroendocrine and immune functions [9]

Methods

Results

Conclusion