Reversal of Diabesity Through Modulating Sympathetic Inputs to Adipose Tissue Following Carotid Body Resection

Abstract

Background and Aims: The development of innovative strategies to treat diabesity and its comorbidities is of major societal importance. The carotid bodies (CB), classically defined as O2 sensors, are also metabolic sensors whose dysfunction contributes to the genesis and progression of metabolic disturbances. Here, we tested the hypothesis that the CBs are key players in the neural hypothalamic-sympathetic circuit controlling glucose and energy homeostasis. Moreover, we investigated if abolishment of CB activity has an anti-diabesity effect in Wistar rats and C75BL/6J mice, associated with increased visceral white and brown adipose tissue (AT) metabolism and the restoration of sympathetic activity within these tissues. Results: We demonstrate that resection of the carotid sinus nerve, the CB-sensitive nerve, promotes weight loss and restores metabolic function in obese rats and mice by enhancing tyrosine hydroxylase expression at the paraventricular nucleus of the hypothalamus and its efferent sympathetic neurons to the AT. Moreover, we found that CSN resection increases sympathetic integration and catecholaminergic action in the AT in a manner that restores or even increases AT metabolism. Conclusion: We provide groundbreaking and innovative data showing a new circuit involving the CB-hypothalamus-sympathetic efferents and the AT in controlling glucose and energy homeostasis and so a novel pathway for managing diabesity.