Metabolic Effects of CCN5/WISP2 Gene Deficiency and Transgenic Overexpression in Mice

Abstract

CCN5/WISP2 is a matricellular protein, the expression of which is under the regulation of Wnt signaling and IGF-1. Our initial characterization supports the notion that CCN5 might promote the proliferation and survival of pancreatic β-cells and thus improve the metabolic profile of the animals. More recently, the roles of endogenous expression of CCN5 and its ectopic, transgenic overexpression on metabolic regulation have been revealed through two reports. Here, we attempt to compare the experimental findings from those studies, side-by-side, in order to further establish its roles in metabolic regulation. Prominent among the discoveries was that a systemic deficiency of CCN5 gene expression caused adipocyte hypertrophy, increased adipogenesis, and lipid accumulation, resulting in insulin resistance and glucose intolerance, which were further exacerbated upon high-fat diet feeding. On the other hand, the adipocyte-specific and systemic overexpression of CCN5 caused an increase in lean body mass, improved insulin sensitivity, hyperplasia of cardiomyocytes, and increased heart mass, but decreased fasting glucose levels. CCN5 is clearly a regulator of adipocyte proliferation and maturation, affecting lean/fat mass ratio and insulin sensitivity. Not all results from these models are consistent; moreover, several important aspects of CCN5 physiology are yet to be explored.

Comprehensive bioinformatics analysis reveals biomarkers of DNA methylation-related genes in varicose veins

“…That WISP2 has been reported to be possibly regulated by the typical Wnt and TGF-β pathways for treatment of obesity and metabolic diseases, and developing new therapeutic strategies (Grünberg et al, 2018). In addition, it is regulated by the Wnt signaling pathway and IGF-1 to improve the metabolic status of animals (Alami and Liu, 2021). It can promote several types of tumors; for example, ovarian cancer cell proliferation by targeting ERK and YAP (Shi et al, 2020).…”

CCN proteins: opportunities for clinical studies—a personal perspective

“…As inflammation figures prominently in all diseases increasing the presence of CCN5 in such tissues sites could have therapeutic value. Alami and Liu (2021) reviewed CCN5 from databases regarding ansgenic mice provided a survey of CCN5. In their Fig.…”

“…Alami and Liu (2021) reviewed CCN5 from databases regarding ansgenic mice provided a survey of CCN5. In their Fig.…”

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

“…Among them, we have demonstrated a significant induction of CCN5/WISP2 gene expression in pancreatic β‐cells by insulin‐like growth factor 1 (IGF‐1), it’s in vitro stimulation on β‐cell proliferation and survival (Chowdhury et al 2014; Kaddour et al 2019), and reviewed possible molecular mechanisms of action of CCN5 within the pancreatic islets (Liu et al 2017). More recently, we reviewed the metabolic consequences of CCN5 gene deficiency and transgenic overexpression in mice (Alami and Liu 2021). A systemic deficiency of CCN5 gene expression caused adipocyte hypertrophy, increased adipogenesis, and lipid accumulation, which resulted in insulin resistance and glucose intolerance, that were further exacerbated upon high‐fat diet feeding (Kim et al 2018).…”

“…IPF and DMD are related to pulmonary fibrosis and increase in connective tissue (fibrosis), respectively, which accompanies muscular disfunction of the affected skeletal myofibers and their force transmission. Additional and more detailed coverage of its pro-fibrotic roles in heart and lung can be found in these recent reports and review (Dorn et al 2018;Alami and Liu 2021;Sun et al 2021).…”