%0 Journal Article
%T Follistatin-Like 1: A Potential Mediator of Inflammation in Obesity
%A Nengguang Fan
%A Haiyan Sun
%A Yufan Wang
%A Yifei Wang
%A Lijuan Zhang
%A Zhenhua Xia
%A Liang Peng
%A Yanqiang Hou
%A Weiqin Shen
%A Rui Liu
%A Jiajing Yin
%A Yongde Peng
%J Mediators of Inflammation
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/752519
%X Obesity is associated with a state of chronic low-grade inflammation, which contributes to insulin resistance and type 2 diabetes. However, the molecular mechanisms that link obesity to inflammation are not fully understood. Follistatin-like 1 (FSTL1) is a novel proinflammatory cytokine that is expressed in adipose tissue and secreted by preadipocytes/adipocytes. We aimed to test whether FSTL1 could have a role in obesity-induced inflammation and insulin resistance. It was found that FSTL1 expression was markedly decreased during differentiation of 3T3-L1 preadipocytes but reinduced by TNF-¦Á. Furthermore, a significant increase in FSTL1 levels was observed in adipose tissue of obese ob/ob mice, as well as in serum of overweight/obese subjects. Mechanistic studies revealed that FSTL1 induced inflammatory responses in both 3T3-L1 adipocytes and RAW264.7 macrophages. The expression of proinflammatory mediators including IL-6, TNF-¦Á, and MCP-1 was upregulated by recombinant FSTL1 in a dose-dependent manner, paralleled with activation of the IKK¦Â-NF¦ÊB and JNK signaling pathways in the two cell lines. Moreover, FSTL1 impaired insulin signaling in 3T3-L1 adipocytes, as revealed by attenuated phosphorylation of both Akt and IRS-1 in response to insulin stimulation. Together, our results suggest that FSTL1 is a potential mediator of inflammation and insulin resistance in obesity. 1. Introduction Obesity has reached epidemic proportions worldwide and affects both adults and children [1]. Accumulating evidence indicates that obesity is associated with chronic low-grade inflammation, characterized by increased proinflammatory cytokine production and accumulation of macrophages in adipose tissue [2¨C4]. Initially viewed as a major site for energy storage, recently it has become evident that adipose tissue is also an important endocrine and immune organ, which secretes a variety of bioactive molecules termed as adipokines [5]. During the development of obesity, the secretory function of adipose tissue changes dramatically. Whereas the secretion of proinflammatory cytokines such as TNF- and IL-6 is increased, the production of anti-inflammatory adipokines/cytokines is reduced [6, 7]. The imbalance between pro- and anti-inflammatory mediators contributes to the chronic inflammation in obesity, which in turn leads to insulin resistance and other obesity-associated diseases [6, 7]. To date, many proinflammatory cytokines, in addition to TNF- and IL-6, have been linked to obesity-induced inflammation and insulin resistance [6¨C8]. Follistatin-like 1 (FSTL1) is a secreted
%U http://www.hindawi.com/journals/mi/2013/752519/