An Update to the WISP-1/CCN4 Role in Obesity, Insulin Resistance and Diabetes

Abstract

Insulin resistance refers to the diminished response of peripheral tissues to insulin and is considered the major risk factor for type 2 diabetes. Although many possible mechanisms have been reported to develop insulin resistance, the exact underlying processes remain unclear. In recent years, the role of adipose tissue as a highly active metabolic and endocrine organ, producing proteins called adipokines and their multidirectional activities has gained interest. The physiological effects of adipokines include energy homeostasis and insulin sensitivity regulation. In addition, an excess of adipose tissue is followed by proinflammatory state which results in dysregulation of secreted cytokines contributing to insulin resistance. Wingless-type (Wnt) inducible signalling pathway protein-1 (WISP-1), also known as CCN4, has recently been described as a novel adipokine, whose circulating levels are elevated in obese and insulin resistant individuals. Growing evidence suggests that WISP-1 may participate in the impaired glucose homeostasis. In this review, we characterize WISP-1 and summarize the latest reports on the role of WISP-1 in obesity, insulin resistance and type 2 diabetes.

Association Between Umbilical Cord Levels of Glypican-1, Glypican-3, Syndecan-1, WISP1, Leptin and Birth Weight of Small, Appropriate, and Large for Gestational Age Infants

“… 17 , 18 WISP1 has been associated with oncogenesis, bone metabolism, and fibrosis of the kidney, lung, and liver. 9 Studies conducted with obese children and adults reported higher circulating WISP1 levels compared with the normal weight healthy controls. 19 , 20 Several studies evaluated serum levels of WISP1 in patients with type 2 diabetes mellitus and reported conflicted results.…”

“… 19 ,21, 22 In addition to its role in obesity, WISP1 was also linked to adipose tissue and systemic inflammation. 9 Ersoy et al 23 reported that body mass index and HOMA-IR independently and positively predicted WISP1 levels in patients with polycystic ovary syndrome. Also, serum WISP1 levels were found higher in pregnant women with GDM than those of the non-GDM healthy pregnant women.…”

Integrated lipid metabolomics and proteomics analysis reveal the pathogenesis of polycystic ovary syndrome

“…CCN4,known as airfoil-free (Wnt) -induced signaling pathway protein-1 (WISP-1), lately been reported as a novel adipokine obese and insulin resistant people have higher quantities of it in their blood.WISP1 is a downstream target protein of Wnt/ β-catenin. Human adipose-derived stem cells' ability to differentiate into adipocytes can be impacted by the control of the Wnt/-catenin signaling pathway, according to research conducted on animals [ 37 ]. WISP1 has been reported to avoid neuronal cell damage and apoptotic degeneration by activating the PI3K/Akt pathway during oxidative damage.…”

Recent progress on the role of cellular communication network factors (CCN) 3, 4 and 6 in regulating adiposity, liver fibrosis and pancreatic islets

“…A recent review has further expanded the role of CCN4 into obesity, adipose inflammation, insulin resistance, as well as in bone protection, and kidney fibrosis (Mirr and Owecki 2021). Regarding the correlation of CCN4 levels with diabetes mellitus, there are still conflicting reports.…”