Abstract
We previously identified a novel gene encoding Favine/CCDC3 (NCBI protein entry NP_083080), a possible secretory factor, the mRNA of which is highly expressed in adipose tissue and the aorta. The Favine mRNA levels are increased in the course of differentiation of rat primary adipocytes and are more elevated in the adipose tissue of genetically obese and diet-induced obese mice than in lean mice. However, its biological function has not yet been elucidated until now. Here, we tested the hypothesis that Favine is involved in lipid metabolism in adipocytes. We found that overexpression of Favine promoted 3T3-L1 adipocyte differentiation. To further investigate the function of Favine in vivo, we generated Favine knock-out (KO) mice. Favine KO mice exhibited a lean phenotype as they aged. The weights of white adipose tissue and liver were less, and adipocyte size was smaller in Favine KO mice compared with wild-type littermates (WT). Expression levels of lipogenic genes, such as fatty-acid synthase (FAS), acetyl-CoA carboxylase α (ACC1), and diacylglycerol O-acyltransferase-2 (Dgat2), were decreased in adipose tissue of Favine KO mice. In 1-year-old mice, Favine deficiency decreased the number of inflammatory cells in white adipose tissue and diminished hepatic steatosis. In vitro, deficiency of Favine attenuated differentiation of primary adipocytes. Taken together, these data demonstrate that Favine has adipogenic and lipogenic effects on adipocytes.
Highlights
Coiled-coil domain-containing 3 (Ccdc3) mRNA is highly expressed in adipose tissue and vessels, but its function remains unknown
We previously identified a novel gene encoding Favine/ CCDC3 (NCBI protein entry NP_083080), a possible secretory factor, the mRNA of which is highly expressed in adipose tissue and the aorta
Retrovirus-mediated Overexpression of Favine Enhanced Adipogenesis and Lipogenesis in 3T3-L1 Cells—To elucidate the functions of Favine in adipocytes, we generated 3T3-L1 cells stably expressing Favine. 3T3-L1 cells were transduced with pMXs-Favine-IRES-green fluorescent protein (GFP) retrovirus (Favine-L1 cells) or pMXs-IRES-GFP retrovirus (Mock-L1 cells)
Summary
Coiled-coil domain-containing 3 (Ccdc3) mRNA is highly expressed in adipose tissue and vessels, but its function remains unknown. We previously identified a novel gene encoding Favine/ CCDC3 (NCBI protein entry NP_083080), a possible secretory factor, the mRNA of which is highly expressed in adipose tissue and the aorta. The Favine mRNA levels are increased in the course of differentiation of rat primary adipocytes and are more elevated in the adipose tissue of genetically obese and diet-induced obese mice than in lean mice. The expression levels of Favine mRNA are increased in murine adipose tissue of genetic and diet-induced obesity models and induced in the course of differentiation of rat primary adipocytes. Ugi et al [13] observed that human omental Favine mRNA is correlated to body mass index and waist circumference These observations suggest that Favine is involved in lipid accumulation, the function of Favine has not been elucidated. We show for the first time that Favine has adipogenic and lipogenic effects by gain-of-function study in murine 3T3-L1 preadipocyte cell line and loss-of-function study in mice
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