Fad24 Causes Hyperplasia in Adipose Tissue and Improves Glucose Metabolism

Yoshikazu Johmura, Kayoko Watanabe, Keishi Kishimoto, Takashi Ueda, Shoichi Shimada, Shigehiro Osada, Makoto Nishizuka, Masayoshi Imagawa
2009 Biological and Pharmaceutical Bulletin  
Obesity is a major risk factor for type 2 diabetes, hypertension, hyperlipidemia, and also arteriosclerosis. 1) The incidence of obesity has been increasing worldwide, and new approaches to treatment are desired. The increase in adipose tissue mass in obese individuals is thought to result from two distinct processes: the formation of new adipocytes from precursor cells (adipocyte differentiation) and an increase in adipocyte size due to fat storage (adipocyte hypertrophy). 2,3) Therefore,
more » ... standing the molecular mechanisms regulating these processes should provide valuable information in the fight to combat the worldwide epidemic of obesity. Over the past two decades, the molecular regulation of adipocyte differentiation has been extensively characterized using the 3T3-L1 and 3T3-F442A preadipocyte cell lines. Notably, attention has centered on the roles of the nuclear receptor peroxisome proliferator-activated receptor g (PPARg) and members of the CCAAT/enhancer-binding protein (C/EBP) family in the mid-and late stages of adipocyte differentiation. 4) These transcription factors are also known to influence adipocyte differentiation in vivo. Moreover, it is becoming clear that adipogenesis is regulated by an elaborate network of transcription factors, transcriptional cofactors, cell-cycle regulators, and signaling intermediates from numerous pathways. 5,6) However, the earliest step in adipogenesis remains largely unknown, although others have recently reported regulators that are important during this period. 7-10) Previously, we isolated 102 genes induced to express at the beginning of the differentiation of 3T3-L1 cells, using the polymerase chain reaction (PCR)-subtraction-cloning method. 11,12) One of them was a novel gene, factor for adipocyte differentiation (fad) 24. Gain-of-function and lossof-function experiments indicated that fad24 promotes 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 b b-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.
doi:10.1248/bpb.32.1656 pmid:19801824 fatcat:pvveufdsvnh4blj24cpzdh54jy