Etanercept Ameliorates Cardiac Fibrosis in Rats with Diet-Induced Obesity.

Chia-Chen Hsu,Chao-Tien Hsu,Mang-Hung Lin,Yingxiao Li,Kai-Chun Cheng,Juei-Tang Cheng,Shang-Wen Chen

doi:10.3390/ph14040320

Abstract

Diet-induced obesity (DIO) is considered the main risk factor for cardiovascular diseases. Increases in the plasma levels of tumor necrosis factor alpha (TNF-α) is associated with DIO. Etanercept, a TNF-α inhibitor, has been shown to alleviate cardiac hypertrophy. To investigate the effect of etanercept on cardiac fibrosis in DIO model, rats on high fat diet (HFD) were subdivided into two groups: the etanercept group and vehicle group. Cardiac injury was identified by classic methods, while fibrosis was characterized by histological analysis of the hearts. Etanercept treatment at 0.8 mg/kg/week twice weekly by subcutaneous injection effectively alleviates the cardiac fibrosis in HFD-fed rats. STAT3 activation seems to be induced in parallel with fibrosis-related gene expression in the hearts of HFD-fed rats. Decreased STAT3 activation plays a role in the etanercept-treated animals. Moreover, fibrosis-related genes are activated by palmitate in parallel with STAT3 activation in H9c2 cells. Etanercept may inhibit the effects of palmitate, but it is less effective than a direct inhibitor of STAT3. Direct inhibition of STAT3 activation by etanercept seems unlikely. Etanercept has the ability to ameliorate cardiac fibrosis through reduction of STAT3 activation after the inhibition of TNF-α and/or its receptor.

Highlights

Obesity is a growing public concern around the world
We found that etanercept is effective to ameliorate cardiac fibrosis in diet-induced obese rats through blockade of tumor necrosis factor-α (TNF)-α to result in reduction of STAT3 activation
We found that etanercept ameliorates the cardiac fibrosis induced by high fat diet (HFD) in rats as assessed by biochemical indicators or pathological determinations

Summary

Introduction

Obesity is a growing public concern around the world. Obesity is considered the main risk factor for many diseases, including cardiovascular diseases, fatty liver, type II diabetes, and cancer [1]. Obesity is linked to the current pandemic of coronavirus disease 2019 (COVID-19) [2]. Individuals with obesity showed significant increases in morbidity and mortality from COVID-19 [3]. In addition to genetic factors, the environmental parameters, including excessive food intake and a sedentary lifestyle, participate in the induction of obesity [4]. The Western-type diet, characterized by a high dietary intake of saturated fats and sucrose, induces atherosclerosis and hyperglycemia [5]

Methods

Results

Discussion

Conclusion