Introduction: Therapeutic options to treat obesity are scarce(1). We previously demonstrated that carotid body (CB) is involved in the genesis of metabolic disturbances by showing that the abolishment of its activity, through resection of carotid sinus nerve (CSN) prevents and reverses metabolic dysfunction(2,3). Furthermore, CSN resection decreased weight gain and body fat mass in an obese animal model(4). Herein, we investigated if these effects are related with a recovery of white (WAT) and brown (BAT) adipose tissues metabolism and a restauration of sympathetic integration. Methods: Experiments were performed in male Wistar rats and C75BL/6 J mice submitted to a high-fat diet (60% lipids) for 10 weeks or 12 weeks, respectively. HF animals were compared with aged-matched controls submitted to standard diet (CTL). After diet period, groups were randomly divided and half submitted to CSN resection or to a sham procedure. Animals were kept under the respective diets for 9 and 3 weeks, respectively. Insulin sensitivity, glucose tolerance, caloric intake and body weight were monitored. At a terminal experiment WAT and BAT depots were collected for: 1) analysis of proteins involved in adipose tissue metabolism (UCP1, PPARγ and PGC1α) by immunohistochemistry and western blot; 2) tissue oxygen consumption rate (OCR) by seahorse in basal conditions and in response to Norepinephrine [15mM] or Dopamine [100nM]; 3) catecholamine levels by HPLC and; 4) sympathetic innervation by light-sheet microscopy. Laboratory care was in accordance with the European Union Directive 2010/63/EU and approved by NOVA Medical School Ethics Committee. Results: HF diet decreased, both in WAT and BAT: 1) the mitochondrial density, by 30% and 21%, respectively and 2) UCP1 expression by 34% and 21%, respectively. It also decreased PGC1α expression by 27%, in WAT, with no alterations observed on PPARγ expression. CSN resection increased, both in WAT and BAT: 1) mitochondrial density by 61 and 50%, respectively and 2) UCP1 expression by 63 and 45%, respectively; It also increased WAT PGC1α and PPARγ expression by 51% and 73% . Moreover, HF diet decreased WAT basal activity by 51% while did not impact BAT basal OCR. CSN resection promoted an increase of 77% above control levels. HF diet also decreased WAT activation promoted by NE and dopamine by 57 and 44%, respectively, while in BAT, HF prompted a decrease of 20% in response to NE with no alterations in OCR after Dopamine injection. CSN resection totally restored the effect of HF diet on NE and dopamine activation of adipose tissue depots. Catecholamine levels, in WAT, were decrease by 47%, with HF diet, while CSN resection increased it by 29%. These results are coincident with the results obtained with light-sheet microscopy were we observed a decrease on sympathetic innervation after HF diet whereas CSN promotes a recovery of innervation. Conclusion: Herein we demonstrated for the 1st time that CB controls adipose tissue metabolism, both WAT and BAT and that the beneficial effects of CSN resection on weight gain and dysmetabolism are related with an improvement of adipose tissue metabolism/thermogenesis accompanied by a restauration of sympathetic integration.