Ccn5, also known as WNT1 inducible signaling pathway protein 2 (WISP2), is a matricellular protein. Its expression is regulated by Wnt signaling and IGF-1. Ccn5 plays important roles in various biological processes, affecting mesenchymal stem cell (MSCs) proliferation and differentiation, and is an important regulator of fibrosis. It is involved in the canonical WNT and TGFβ pathways, and is regulated by the adipogenic commitment factor BMP4 [1,3].

Systemic deficiency of the Ccn5 gene in mice caused adipocyte hypertrophy, increased adipogenesis, lipid accumulation, insulin resistance, and glucose intolerance, which were exacerbated by a high-fat diet. In contrast, adipocyte-specific and systemic overexpression of Ccn5 led to an increase in lean body mass, improved insulin sensitivity, cardiomyocyte hyperplasia, increased heart mass, and decreased fasting glucose levels. These findings from gene knockout (KO) and over-expression mouse models indicate that Ccn5 is a regulator of adipocyte proliferation and maturation, influencing the lean/fat mass ratio and insulin sensitivity [2].

In conclusion, Ccn5 is a crucial regulator in metabolic processes, especially in adipocyte biology and insulin sensitivity. The use of Ccn5 KO and over-expression mouse models has revealed its significance in metabolic diseases such as obesity and type 2 diabetes, providing potential targets for developing new treatment strategies in these disease areas.