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Reversal of Diabesity Through Modulating Sympathetic Inputs to Adipose Tissue Following Carotid Body Resection
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Resumo(s)
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.
Descrição
21\u2010CE18\u20100016 from France and the Horizons Europe PASGRAS project (ref 101080329). Moreover, it was supported by the Research Unit UID/04462: iNOVA4Health\u2014Programa de Medicina Translacional, by the Associated Laboratory LS4FUTURE (LA/P/0087/2020), and BM was funded with a PhD Grant (PD/BD/128336/2017) and JFS, FOM with contracts CEEC IND/02428/2018 and CEECIND/04266/2017, all financially supported by Funda\u00E7\u00E3o para a Ci\u00EAncia e Tecnologia/Minist\u00E9rio da Educa\u00E7\u00E3o, Ci\u00EAncia e Inova\u00E7\u00E3o, Portugal. Funding:
Publisher Copyright:
© 2025 The Author(s). Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.
Palavras-chave
adipose tissue carotid body catecholaminergic signaling energy expenditure metabolic diseases sympathetic nervous system Physiology