WISP1 Is a Marker of Systemic and Adipose Tissue Inflammation in Dysmetabolic Subjects With or Without Type 2 Diabetes

Abstract

Context:Wnt1-inducible signaling pathway protein 1 (WISP1) is a novel adipokine participating in adipose tissue (AT) dysfunction; so far, no data on WISP1 in diabetes are available.Objectives:To evaluate plasma WISP1 in subjects with type 2 diabetes (T2D) and its correlates linked to AT inflammation.Design and Participants:For this cross-sectional study, 97 consecutive dysmetabolic patients were recruited at the diabetes outpatient clinics of Sapienza University in Rome; 71 of them had T2D, with (n = 35) or without (n = 36) obesity, and 26 were obese patients without diabetes. Twenty-one normal-weight nondiabetic individuals were enrolled as a control group. Study participants underwent clinical workup and blood sampling for metabolic/inflammatory characterization; magnetic resonance imaging (MRI) data on subcutaneous AT and visceral AT (VAT) area, hepatic fat content, and VAT homogeneity were available for most diabetic patients.Results:Plasma WISP1 significantly increased throughout classes of obesity and correlated with greater VAT area, interleukin-8 (IL-8), and lower adiponectin levels, without differing between diabetic and nondiabetic participants. Higher IL-8 was the main determinant of increased WISP1. MRI-assessed VAT inhomogeneity was associated with higher WISP1, IL-8 and C-reactive protein levels, independent of obesity; high WISP1 strongly predicted VAT inhomogeneity (P < 0.001).Conclusions:WISP1 levels are increased in obese persons and are directly related to adiposity, independent of glycemic status or insulin resistance; moreover, they are strongly associated with increased plasma IL-8 and signal abnormalities of VAT. The overall data add insights to the mechanisms underlying metabolic alterations and may open a scenario for innovative therapeutic approaches for diabetes prevention and care.

The novel adipokine WISP1 associates with insulin resistance and impairs insulin action in human myotubes and mouse hepatocytes

“…In vitro studies on primary hSkMCs as well as the mouse hepatocyte cell line AML12 showed that recombinant WISP1 directly impaired insulin action by inhibiting the Akt signalling pathway. The increased WISP1 expression in VAT of obese men is in line with previous reports from our group and others [13][14][15]26] suggesting that WISP1 expression is regulated by body weight. High-fat feeding in mice increased the expression of WISP1 in adipose tissue [13,27] while diet-induced weight loss in humans lowered WISP1 expression in adipose tissue [13].…”

“…A study in women with gestational diabetes and insulin resistance showed increased circulating levels of WISP1 and identified BMI and insulin resistance as determinants of WISP1 levels [14]. Another very recently published study observed a direct relationship between circulating WISP1 levels and visceral adiposity and signs of insulin resistance, independently of glucose tolerance [15].…”

Association of WISP1/CCN4 with Risk of Overweight and Gestational Diabetes Mellitus in Chinese Pregnant Women

“…Two previous studies examined the association between circulating WISP1 and adult obesity status. One showed that WISP1 was sub-stantially overexpressed in visceral fat from obese subjects and reflected insulin resistance and inflammation of adipose tissue [18], whereas another study found that WISP1 levels increased in obese persons and were directly associated with adiposity, independent of glycemic status or insulin resistance [17]. In contrast, our findings demonstrated that prepregnancy overweight/obesity interacted with GDM to affect circulatory concentration of WISP1 (Figure 1(b)).…”

“…WISP1 is involved in a wide range of biological functions and pathological processes, such as cell growth, differentiation, and survival [13,14]. And overexpressed WISP1 has been observed in several diseases including GDM [15], hypertension [16], obesity [17,18], lung fibroblasts [19], and several types of cancer [20]. WISP1 is widely expressed in normal tissues, particularly in human adipose tissue.…”

Remodeling adipose tissue inflammasome for type 2 diabetes mellitus treatment: Current perspective and translational strategies

“…The proinflammatory potential of the adipokine was exhibited in vitro, when macrophages treated with WISP1 caused increased secretion of proinflammatory cytokines in a dose‐dependent fashion and polarized them to M1 phenotype . Serum concentration of the adipokine is elevated in obesity, irrespective of glycemia or insulin resistance status . This observation was reinforced in a different study, where WISP1 levels were found elevated in obese men irrespective of glycemic status compared with nonobese men .…”