Cannabinoid CB1 Receptor Deletion from Catecholaminergic Neurons Protects from Diet-Induced Obesity

• Published in: International journal of molecular sciences 2022-10, Vol.23 (20), p.12635
• Main Authors: Srivastava, Raj Kamal, Ruiz de Azua, Inigo, Conrad, Andrea, Purrio, Martin, Lutz, Beat
• Format: Article
• Language: English
• Subjects: Adipocytes; Adipogenesis; Adipose tissue; Adipose tissue (brown); Adrenergic receptors; Body fat; Body weight gain; Cannabinoid CB1 receptors; Cannabinoids; catecholaminergic neurons; CB1 receptor; Clonal deletion; Corticosterone; Diet; Dopamine; Endocannabinoid system; Energy; Energy balance; Gene expression; Homeostasis; Hormones; Hydroxylase; Hypothalamic-pituitary-adrenal axis; Hypothalamus; Metabolic disorders; Metabolic syndrome; Mutants; Neurons; Neuropeptide Y; Norepinephrine; Obesity; Phosphorylation; Pituitary; Plasma; Proteins; Risk analysis; Risk factors; Rodents; Sympathetic nervous system; Thermogenesis
• ISSN: 1422-0067; 1661-6596; 1422-0067
• 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 (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.