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.

Cardiac Myocyte-Derived Follistatin-Like 1 Prevents Renal Injury in a Subtotal Nephrectomy Model

“…15 Treatment of cultured adipocytes with TNF-a leads to increased expression of Fstl1. 56 Thus, it is plausible that Fstl1 is a counter-regulatory, anti-inflammatory cardiokine that is induced by stress, in particular ischemia and inflammation, and mitigates this damage in the heart and remote tissues. In the present study, plasma Fstl1 levels were increased after subtotal nephrectomy in control mice, whereas this increase was largely abolished in cardiac-specific Fstl1-KO mice.…”

Beyond the bone: Bone morphogenetic protein signaling in adipose tissue

“…It was enriched in 3T3‐L1 preadipocytes and decreased as adipogenesis induction occurs; conversely, it reappeared when adipocytes were dedifferentiated . A significant increase of follistatin‐like was observed in adipose tissue of ob / ob mice as well as in the serum of overweight and obese individuals . Mice with deletion of Follistatin‐like 3 had enhanced glucose tolerance and insulin sensitivity and their perigonadal visceral fat pad was reduced in size …”

Structural and functional study of FK domain of Fstl1

“…7 Fstl1 has been implicated in several human diseases. Findings on Fstl1 in cardiovascular disease, 7,8 cancer, [9][10][11] arthritis, [12][13][14][15][16] lung fibrosis, 17 and obesity 18,19 emphasize its potential as both biomarkers and targets for the management of the disease process. Although the functions and mechanisms of Fstl1 have not been completely understood, a growing body of literatures have identified the critical roles of Fstl1 in the regulation of cell survival, 20,21 proliferation, 22,23 differentiation, 20,22 migration, 23,24 as well as inflammation, 16 and immune modulation.…”