Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University of Mainz, 55128 Mainz, Germany.
Department of Zoology, Indira Gandhi National Tribal University, Amarkantak, Anuppur 484887, India.
Int J Mol Sci. 2022 Oct 20;23(20):12635. doi: 10.3390/ijms232012635.
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 ()-expressing cells in the regulation of SNS activity. In a diet-induced obesity model, 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 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.
高热量饮食和慢性应激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）的活性。本研究表明，大麻素 1 型受体（CB1）在多巴胺 β-羟化酶（）表达细胞中在调节 SNS 活性中起关键作用。在饮食诱导的肥胖模型中，从这些细胞中缺失可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，从而导致白色脂肪组织中的脂肪生成减少和棕色脂肪组织中的产热增加。儿茶酚胺能神经元中 缺失会增加血浆去甲肾上腺素水平、去甲肾上腺素周转率和内脏脂肪中的交感神经活性，这与突变小鼠内脏脂肪中的神经肽 Y（NPY）水平降低相一致。此外，突变小鼠的血浆皮质酮水平降低。我们的研究提供了内源性大麻素系统在调节能量平衡中的作用的机制的新见解，其中 dbh 阳性细胞中的 CB1 缺失通过多种机制（如增加 SNS 活性、降低 NPY 活性和降低基础下丘脑-垂体-肾上腺（HPA）轴活性）来防止饮食诱导的体重增加。
