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Publication : CREG1 stimulates brown adipocyte formation and ameliorates diet-induced obesity in mice.

First Author  Hashimoto M Year  2019
Journal  FASEB J Volume  33
Issue  7 Pages  8069-8082
PubMed ID  30917000 Mgi Jnum  J:292429
Mgi Id  MGI:6442986 Doi  10.1096/fj.201802147RR
Citation  Hashimoto M, et al. (2019) CREG1 stimulates brown adipocyte formation and ameliorates diet-induced obesity in mice. FASEB J 33(7):8069-8082
abstractText  Increased formation of brown and beige adipocytes is critical for adaptive thermogenesis to maintain homeothermy in cold or to circumvent diet-induced obesity (DIO). Cellular repressor of adenovirus early region 1A-stimulated genes 1 (CREG1) exhibits the ability to stimulate brown adipogenesis, including the induction of uncoupling protein 1 (UCP1), in vitro. Thus, we aimed to clarify whether CREG1 promotes brown adipocyte formation and inhibits DIO at the whole-animal level. In mouse brown adipose tissue (BAT), CREG1 expression was markedly increased in cold but was decreased under thermoneutrality, suggesting CREG1 involvement in BAT thermogenesis. Moreover, in BAT and white adipose tissue, expression of UCP1 and fibroblast growth factor-21 and browning were both significantly higher in adipocyte P2-Creg1-transgenic (Tg) mice than in wild-type (WT) littermates. Following stimulation with a beta3-adrenergic agonist, energy consumption was elevated in the Tg mice, which showed increased resistance to DIO and improvement of obesity-associated complications including fatty liver relative to WT mice. The CREG1 stimulatory effect on brown adipogenesis was confirmed in Tg-BAT primary cultures. It was also found that CREG1 binds to retinoid X receptor alpha, which interacts with thyroid hormone receptor for brown adipogenesis. Our findings demonstrate that CREG1 stimulates brown adipocyte formation and browning, ameliorating obesity and its related pathology in vivo.-Hashimoto, M., Kusudo, T., Takeuchi, T., Kataoka, N., Mukai, T., Yamashita, H. CREG1 stimulates brown adipocyte formation and ameliorates diet-induced obesity in mice.
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