Abstract
Long-term cytokine-mediated inflammation is a risk factor for obesity and type 2 diabetes mellitus (T2DM). Our previous studies reveal significant associations between promoter single nucleotide polymorphisms (SNPs) of interleukin (IL)-4 and T2DM, as well as between SNPs in genes encoding IL-4/IL-4 receptor and high density lipoproteins. Our animal study reveals that IL-4 regulates glucose/lipid metabolism by promoting glucose tolerance and inhibiting lipid deposits. The above results strongly suggest the involvement of IL-4 in energy homeostasis. In the present study, we focus on examining the regulatory mechanism of IL-4 to lipid metabolism. Our results show that IL-4 inhibits adipogenesis by downregulating the expression of peroxisome proliferator-activated receptor-γ and CCAAT/enhancer-binding protein-α. Additionally, IL-4 promotes lipolysis by enhancing the activity and translocation of hormone sensitive lipase (HSL) in mature adipocytes, which suggests that IL-4 plays a pro-lipolytic role in lipid metabolism by boosting HSL activity. Our results demonstrate that IL-4 harbors pro-lipolysis capacity by inhibiting adipocyte differentiation and lipid accumulation as well as by promoting lipolysis in mature adipocytes to decrease lipid deposits. The above findings uncover the novel roles of IL-4 in lipid metabolism and provide new insights into the interactions among cytokine/immune responses, insulin sensitivity, and metabolism.
Highlights
Long-term cytokine-mediated inflammation is a risk factor for obesity and type 2 diabetes mellitus (T2DM)
Results of Oil Red O (ORO) staining showed that lipid accumulation in differentiated cells was inhibited by ف30% in the presence of IL-4 treatment (Fig. 1A, B)
To further verify the inhibitory effects of IL-4 toward adipogenesis, we examined whether TZD treatment could rescue the differentiation of IL-4-treated adipocytes
Summary
Long-term cytokine-mediated inflammation is a risk factor for obesity and type 2 diabetes mellitus (T2DM). Obesity is characterized by an expansion of white adipose tissue (WAT) mass resulting from increased adipocyte number and/or size [1]. It is a key risk factor leading to type 2 diabetes mellitus (T2DM) and hyperlipidemia, and has become a pan-endemic health problem with rapidly growing global incidence [2, 3]. Abundant studies have linked the increased production of inflammatory cytokines, such as tumor necrosis factor-␣ (TNF-␣), interleukin (IL)-6, and certain adipokines, during the inflammatory process to obesity, as well as to the development of insulin resistance [6,7,8].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
