WISP1 Is a Novel Adipokine Linked to Inflammation in Obesity

Abstract

WISP1 (Wnt1-inducible signaling pathway protein-1, also known as CCN4) is a member of the secreted extracellular matrix–associated proteins of the CCN family and a target gene of the Wingless-type (WNT) signaling pathway. Growing evidence links the WNT signaling pathway to the regulation of adipogenesis and low-grade inflammation in obesity. We aimed to validate WISP1 as a novel adipokine. Human adipocyte differentiation was associated with increased WISP1 expression and secretion. Stimulation of human macrophages with WISP1 led to a proinflammatory response. Circulating WISP1 and WISP1 subcutaneous adipose tissue expression were regulated by weight changes in humans and mice. WISP1 expression in visceral and subcutaneous fat tissue was associated with markers of insulin resistance and inflammation in glucose-tolerant subjects. In patients with nonalcoholic fatty liver disease, we found no correlation among disease activity score, liver fat content, and WISP1 expression. Insulin regulated WISP1 expression in adipocytes in vitro but had no acute effect on WISP1 gene expression in subcutaneous fat tissue in overweight subjects who had undergone hyperinsulinemic clamp experiments. The data suggest that WISP1 may play a role in linking obesity to inflammation and insulin resistance and could be a novel therapeutic target for obesity.

Wisp1 mediates Bmp3-stimulated mesenchymal stem cell proliferation

“…Using DNA microarray, we first identified genes that were differentially regulated by Bmp3. Prominently among the upregulated genes was Wisp1, the increased expression of which is known to be associated with human adipocyte differentiation (Murahovschi et al 2015). Wisp1 is also a pro-survival factor, because it stimulates proliferation of several non-adipose cell types, including cardiac fibroblasts (Venkatachalam et al 2009), lung epithelial cells (Königshoff et al 2009), osteogenic cells (Inkson et al 2009).…”

“…Given that Wisp1 was upregulated following Bmp3 treatment and is a known pro-survival factor in various nonadipose cell types (Inkson et al 2009, Königshoff et al 2009, Venkatachalam et al 2009, Schlegelmilch et al 2014, coupled with previous findings that human adipocyte differentiation was associated with elevated Wisp1 expression (Murahovschi et al 2015), we examined the involvement of Wisp1 in mediating Bmp3-induced MSC proliferation. We first determined if Bmp3-induced upregulation of Wisp1 expression preceded Bmp3-stimulated cell proliferation by conducting a time-dependent experiment.…”

WISP1i

“…Expression of WISP1 also is increased during human adipocyte differentiation (Murahovschi et al 2015). WISP1 expression is altered by weight change in humans and increases during insulin resistance in glucosetolerant individuals (Murahovschi et al 2015), suggestive that WISP1 may represent an important reparative process in individuals with DM.…”

“…Expression of WISP1 also is increased during human adipocyte differentiation (Murahovschi et al 2015). WISP1 expression is altered by weight change in humans and increases during insulin resistance in glucosetolerant individuals (Murahovschi et al 2015), suggestive that WISP1 may represent an important reparative process in individuals with DM. However, WISP1 expression has recently been linked to gestational diabetes with additional studies required to determine its role in this disorder (Sahin Ersoy et al 2016).…”

It’s all in your gut and mind

“…Finally, as this is JCCS, let's not overlook interesting and relevant studies on CCN2 and WISP1-CCN4 and WISP2, contributing to our understanding of adipogenesis and inflammation in adipose tissue, an immune cell contribution (Tan et al 2013;Murahovschi et al 2014;Gruneberg et al 2014), and the still underappreciated concept of hormetic effects of everyday polyphenols, like resveratrol in red wine, on obesity (Scapagnini et al 2014).…”