Investigation in the mechanism of regulation of voluntary exercise and abdominal visceral fat accumulation by monoamines.

我们建立了一种新的动物模型，称为SPORTS（自发跑步德岛四国）大鼠，显示高肾上腺素（Epi）水平。本研究的目的是研究在体内Epi对乙酰辅酶A羧化酶（ACC）和腹部内脏脂肪积累的影响。我们将6周龄雄性对照组和运动组大鼠分为两组，分别饲喂正常饲料和高脂高糖饲料（HFS）16周。各组之间的食物摄入量没有差异，但在两个饮食组中，SPORTS大鼠的体重增加均显着低于对照组大鼠。饮食治疗10周后，葡萄糖耐量试验（GTT）显示，SPORTS大鼠的胰岛素敏感性增加。此外，SPORTS大鼠的腹部脂肪和血浆甘油三酯（TG）含量均较低。在SPORTS大鼠的腹部脂肪中，观察到ACC Ser-79磷酸化升高，并被β-肾上腺素能受体（AR）拮抗剂普萘洛尔或AMP活化蛋白激酶（AMPK）抑制剂化合物C抑制。结果表明，高水平的Epi通过β-AR和AMPK信号通路诱导SPORTS大鼠腹部内脏脂肪中ACC磷酸化，这可能有助于减少腹部内脏脂肪堆积，提高胰岛素敏感性。我们的研究结果表明，β-AR调节的ACC活性可能是治疗生活方式相关疾病（如肥胖）的靶点。

We established a new animal model called SPORTS (Spontaneously-Running Tokushima-Shikoku) rats, which show high-epinephrine (Epi) levels. The aim of this study was to investigate the in vivo effect of Epi on acetyl-CoA carboxylase (ACC) and abdominal visceral fat accumulation. We divided both 6-week male control and SPORTS rats into two groups, which were fed either normal diet or high fat and sucrose (HFS) diet for 16 weeks. Food intake was not different among the groups, but SPORTS rats showed significantly lower weight gain than control rats in both diet groups. After 10 weeks of diet treatment, glucose tolerance tests (GTTs) revealed that SPORTS rats had increased insulin sensitivity. Furthermore, SPORTS rats had lower quantities of both abdominal fat and plasma triglyceride (TG). In abdominal fat, elevated ACC Ser-79 phosphorylation was observed in SPORTS rats and suppressed by an antagonist of β-adrenergic receptor (AR), propranolol, or an inhibitor of AMP-activated protein kinase (AMPK), Compound C. From these results, high level of Epi induced ACC phosphorylation mediated through β-AR and AMPK signaling pathways in abdominal visceral fat of SPORTS rats, which may contribute to reduce abdominal visceral fat accumulation and increase insulin sensitivity. Our results suggest that β-AR-regulated ACC activity would be a target for reating lifestyle-related diseases, such as obesity.