抄録
Noradrenaline released from sympathetic nerve terminals causes lipolysis and thermogenesis via activation of β3- adrenergic receptor, subsequent signaling and uncoupling protein (UCP) in brown adipocytes, regulating body temperature and energy balance. Watanabe et al. (2006, Nature, 439, 486) recently suggested cholic acid intake prevents obesity in high fat diet-fed mice via enhancement of the expression of D2, an enzyme that converts T4 (thyroxin) to T3. We have studied whether this preventive effect of cholic acid on obesity formation is caused by enhanced thermogenesis via β3-adrenergic lipolysis and α1- and β3-adrenergic Ca2+ signaling. Changes in intracellular Ca2+ ([Ca2+]i), mitochondrial membrane potential and heat production were recorded by fluorometry and thermography in mice fed with high fat diet, high fat diet with cholic acids or chow for 7-9 weeks. Expression of proteins and mRNA of adrenergic receptor were also examined. Abnormal increases in body weight by high fat diet were prevented by cholic acid intake. Cholic acids-fed mice showed a greater heat production, greater FCCP-, α1- and β3-adrenergic rises in [Ca2+]i, tighter mitochondria-endoplasimic reticulum couplings and greater expression of α1- and β3-adrenoceptor proteins in brown adipocytes. Thus, cholic acid intake prevents high fat diet-induced obesity by increasing energy expenditure via increased adrenergic signaling in brown adipocytes. [J Physiol Sci. 2008;58 Suppl:S105]
