Abstract

The accumulation and differentiation of adipocytes contribute to the development of obesity and metabolic diseases. It is well-known that interactions of transcription factors such as peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer binding protein α (C/EBPα), and endoplasmic reticulum (ER) stress are required for adipogenesis. Recently, use of nonthermal atmospheric plasma (NTP) is expanding from the biomedical field into various other fields. In this study, we investigated whether nonthermal plasma-treated solution (NTS) has an inhibitory effect on adipogenesis and elucidated its mechanisms. Our results demonstrated that NTS significantly inhibited pre-adipocyte differentiation into adipocytes based on Oil Red O staining and triglyceride accumulation. Moreover, NTS treatment suppressed the mRNA and protein expression levels of key adipogenic transcription factors, and adipocyte-specific genes. NTS also down-regulated endoplasmic reticulum stress-related proteins. Consistent with in vitro studies, an animal study using a mouse model of diet-induced obesity showed that NTS treatment reduced body weight and fat, ER stress/UPR, triglyceride, and adipogenic marker level without altering food intake. These findings indicate that NTS inhibits adipogenic differentiation, and provide a mechanistic explanation of the inhibitory effect of NTS on adipogenesis. Taken together, our results suggest that NTS might be useful to treat obesity and obesity-related diseases.

Highlights

  • Obesity is one of the most common metabolic disorders worldwide; it has been suggested that obesity is directly related to increased prevalence of various adult diseases such as type 2 diabetes, hypertension, hyperlipidemia, heart disease, and cancer[1]

  • These results suggest that endoplasmic reticulum (ER) stress and unfolding protein response (UPR) activation are among the essential components of adipogenesis

  • Results of this study demonstrated that nonthermal plasma-treated solution (NTS) inhibited the expression of adipogenic transcription factor and adipocyte-associated genes, lipid accumulation, and triglyceride contents in pre-adipocytes, suggesting that NTS might be useful for inhibiting obesity

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Summary

Introduction

Obesity is one of the most common metabolic disorders worldwide; it has been suggested that obesity is directly related to increased prevalence of various adult diseases such as type 2 diabetes, hypertension, hyperlipidemia, heart disease, and cancer[1]. Obesity is a metabolic disease that occurs due to unbalanced intake and consumption of calories It is characterized by increased adipose cell size (hypertrophy) or number (hyperplasia)[2]. CCAAT/enhancer binding protein α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ) are two well-known adipogenic transcription factors that regulate adipogenic differentiation[3,4,5]. C/EBP transcription factors stimulate the expression of PPARγ and C/EBPα, which cross-regulate each other to induce adipocyte-specific expression of genes such as FAT, FAS, and ACC6,7. This gene expression stimulates the formation of mature adipocytes with triglyceride accumulation and lipid droplet formation. It has been suggested that during adipogenesis ER stress markers such as protein kinase RNA-like endoplasmic reticulum kinase (PERK), inositol requiring enzyme 1 (IRE1), and activating transcription factor 6 (ATF6) are upregulated in adipocytes and adipose tissue[11,12,13]

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