Ablation of carotid body activity reverses diabesity by improving white and brown adipose tissue sympathetic innervation and metabolism

Summary Finding novel pathological mechanisms that lead to innovative strategies to treat obesity and its associated illness are critically needed. The carotid bodies (CB) are metabolic sensors whose dysfunction contributes to insulin resistance and glucose intolerance development. Herein, we find that the ablation of CB activity, through resection of carotid sinus nerve (CSN) promotes weight loss and restores metabolic function in high fat (HF) rodents, by increasing WAT basal metabolism and by restoring WAT and BAT sympathetic activation. Moreover, we found that CSN resection rescues adipose tissue sympathetic/catecholamine resistance present in obesity states. Additionally, we found that the CB signals integrated in the paraventricular nucleus of the hypothalamus are decreased in obesity states and that CSN denervation in HF animals restore neuronal activity in this region. By inducing energy expenditure via the increase in WAT and BAT metabolism, CB modulation might be used as a therapeutic target for obesity and dysmetabolism. Highlights Ablation of carotid body (CB) activity promotes weight loss Carotid body modulates white and brown adipose tissue metabolism Ablation of CB activity rescues adipose tissue sympathetic resistance in obesity Carotid sinus nerve resection restored the altered neuronal activity induced by obesity in the paraventricular nucleus of the hypothalamus