Fad24 Causes Hyperplasia in Adipose Tissue and Improves Glucose Metabolism

Abstract

We have previously reported that a novel gene, factor for adipocyte differentiation (fad) 24, promotes adipogenesis in vitro. To examine the role of fad24 in adipogenesis in vivo and the development of obesity, transgenic mice overexpressing fad24 were generated using mouse fad24 cDNA under the control of a chicken beta-actin promoter and cytomegalovirus enhancer. The comparison of the ability of fibroblasts from fad24 transgenic embryos to differentiate into adipocytes with that of fibroblasts from wild-type embryos revealed that fad24 overexpression promotes adipogenesis in embryonic fibroblasts. The weight and histology of white adipose tissues, and serum adipocytokine levels were compared between fad24 transgenic mice and wild-type mice, and we found that fad24 overexpression increased the number of smaller adipocytes, caused hyperplasia rather than hypertrophy in white adipose tissue and increased the serum adiponectin level in mice fed both normal chow and a high-fat diet. Glucose and insulin tolerance tests indicated that the activity for glucose metabolism is improved in fad24 transgenic mice fed normal chow in comparison with that in wild-type mice. Our findings suggest that fad24 is a positive regulator of adipogenesis in vivo. Moreover, the increase in the number of smaller adipocytes caused by the overexpression of fad24 appears to enhance glucose metabolic activity, perhaps by increasing the serum adiponectin level.