Abstract：
High-calorie diets and chronic stress are major contributors to the development of obesity and metabolic disorders. These two risk factors regulate the activity of the sympathetic nervous system (SNS). The present study showed a key role of the cannabinoid type 1 receptor (CB1) in dopamine β-hydroxylase (dbh)-expressing cells in the regulation of SNS activity. In a diet-induced obesity model, CB1 deletion from these cells protected mice from diet-induced weight gain by increasing sympathetic drive, resulting in reduced adipogenesis in white adipose tissue and enhanced thermogenesis in brown adipose tissue. The deletion of CB1 from catecholaminergic neurons increased the plasma norepinephrine levels, norepinephrine turnover, and sympathetic activity in the visceral fat, which coincided with lowered neuropeptide Y (NPY) levels in the visceral fat of the mutant mice compared with the controls. Furthermore, the mutant mice showed decreased plasma corticosterone levels. Our study provided new insight into the mechanisms underlying the roles of the endocannabinoid system in regulating energy balance, where the CB1 deletion in dbh-positive cells protected from diet-induced weight gain via multiple mechanisms, such as increased SNS activity, reduced NPY activity, and decreased basal hypothalamic-pituitary-adrenal (HPA) axis activity.
摘要：
高热量饮食和慢性压力是肥胖和代谢紊乱发展的主要原因。这两个危险因素调节交感神经系统（SNS）的活动。本研究表明，多巴胺β-羟化酶（dbh）表达细胞中大麻素1型受体（CB1）在SNS活性调节中的关键作用。在饮食诱导的肥胖模型中，从这些细胞中删除CB1通过增加交感神经驱动来保护小鼠免受饮食诱导的体重增加，导致白色脂肪组织的脂肪生成减少，棕色脂肪组织的产热增强。儿茶酚胺能神经元中CB1的缺失增加了血浆去甲肾上腺素水平，去甲肾上腺素周转,内脏脂肪的交感神经活动，与对照组相比，突变小鼠内脏脂肪中神经肽Y（NPY）水平降低。此外，突变小鼠显示血浆皮质酮水平降低。我们的研究为内源性大麻素系统在调节能量平衡中的作用机制提供了新的见解。dbh阳性细胞中的CB1缺失通过多种机制保护免受饮食诱导的体重增加，例如增加SNS活动，NPY活性降低，基础下丘脑-垂体-肾上腺（HPA）轴活性降低。
