title: Follistatin-like 1: a potential mediator of inflammation in obesity.
abstract: 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-α. 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-α, and MCP-1 was upregulated by recombinant FSTL1 in a dose-dependent manner, paralleled with activation of the IKKβ-NFκB 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.
authors.affiliation: Department of Endocrinology, Shanghai First People's Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai 200080, China ; Department of Endocrinology, Shanghai Songjiang Center Hospital, 746 Zhongshan Zhong Road, Shanghai 201600, China.
authors.forename: Nengguang
authors.initials: N
authors.lastname: Fan
authors.affiliation: Department of Endocrinology, Shanghai First People's Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai 200080, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Endocrinology, Shanghai First People's Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai 200080, China.
authors.forename: Yufan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, Shanghai First People's Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai 200080, China.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, Shanghai Songjiang Center Hospital, 746 Zhongshan Zhong Road, Shanghai 201600, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology, Shanghai Songjiang Center Hospital, 746 Zhongshan Zhong Road, Shanghai 201600, China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Xia
authors.affiliation: Department of Laboratory Medicine, Shanghai Songjiang Center Hospital, 746 Zhongshan Zhong Road, Shanghai 201600, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Peng
authors.affiliation: Department of Laboratory Medicine, Shanghai Songjiang Center Hospital, 746 Zhongshan Zhong Road, Shanghai 201600, China.
authors.forename: Yanqiang
authors.initials: Y
authors.lastname: Hou
authors.affiliation: Department of Medical Examination, Shanghai Songjiang Center Hospital, 746 Zhongshan Zhong Road, Shanghai 201600, China.
authors.forename: Weiqin
authors.initials: W
authors.lastname: Shen
authors.affiliation: Department of Endocrinology, Shanghai First People's Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai 200080, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Endocrinology, Shanghai First People's Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai 200080, China.
authors.forename: Jiajing
authors.initials: J
authors.lastname: Yin
authors.affiliation: Department of Endocrinology, Shanghai First People's Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai 200080, China.
authors.forename: Yongde
authors.initials: Y
authors.lastname: Peng
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000276:immunology; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D038702:Follistatin-Related Proteins / Q000032:analysis / Q000502:physiology*; D006801:Humans; D051550:I-kappa B Kinase / Q000502:physiology; D007249:Inflammation / Q000209:etiology*; D018836:Inflammation Mediators / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000502:physiology; D009765:Obesity / Q000150:complications*; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D038702:Follistatin-Related Proteins; D018836:Inflammation Mediators; D007328:Insulin; D016328:NF-kappa B; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D051550:I-kappa B Kinase