Narishima Ryota, Yamasaki Masahiro, Hasegawa Shinya, Fukui Tetsuya
Department of Health Chemistry, Hoshi University, Tokyo, Japan.
Obesity (Silver Spring). 2009 Mar;17(3):611-5. doi: 10.1038/oby.2008.566. Epub 2008 Dec 11.
Obesity causes various physiological disorders between the central nervous system and peripheral tissues. Ketone bodies have a neuro-protective role and are strongly affected by obesity-related metabolic disorders. To clarify the effects of obesity on ketone body utilization in brain, we examined the mRNA localization of acetoacetyl-CoA synthetase (AACS), which activates ketone bodies for the synthesis of fatty acid and cholesterol, in various brain regions of Zucker fatty rats by in situ hybridization. The AACS mRNA level was increased in the paraventricular thalamic nucleus (PVT) but not affected in the cerebrum and hippocampus in Zucker fatty rats. In contrast, the AACS mRNA level was reduced in the arcuate hypothalamic nucleus (Arc) and ventromedial hypothalamic nucleus (VMH) in the hypothalamus. Succinyl-CoA:3-oxoacid CoA-transferase (SCOT) mRNA level was decreased only in the PVT but not affected in the Arc and VMH. These data raise the possibility that AACS is regulated by the leptin signaling pathway in the hypothalamus but not in the PVT. As AACS was expressed in neural-like cells, ketone bodies are assumed to be utilized for the synthesis of lipidic substances and to cause metabolic disorders in the nervous system.
肥胖会导致中枢神经系统与外周组织之间出现各种生理紊乱。酮体具有神经保护作用，并受到肥胖相关代谢紊乱的强烈影响。为了阐明肥胖对大脑中酮体利用的影响，我们通过原位杂交技术检测了在Zucker肥胖大鼠的各个脑区中，使酮体活化以合成脂肪酸和胆固醇的乙酰乙酰辅酶A合成酶（AACS）的mRNA定位。在Zucker肥胖大鼠中，丘脑室旁核（PVT）中的AACS mRNA水平升高，但大脑和海马体中的AACS mRNA水平未受影响。相比之下，下丘脑弓状核（Arc）和腹内侧下丘脑核（VMH）中的AACS mRNA水平降低。琥珀酰辅酶A：3-氧代酸辅酶A转移酶（SCOT）的mRNA水平仅在PVT中降低，而在Arc和VMH中未受影响。这些数据提示，AACS在下丘脑而非PVT中受瘦素信号通路调控。由于AACS在神经样细胞中表达，因此推测酮体可用于合成脂质物质并导致神经系统代谢紊乱。
