Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCA238

Poster Communications

Carotid sinus nerve resection reduces weight gain and improves metabolic function in high-fat animals via an increase in brown adipose tissue function and decrease in its inflammation

C. S. Prego1, B. S. F.Melo1, J. F. Sacramento1, S. V. Conde1

1. CEDOC, Nova Medical School, Lisboa, Portugal.

Background and aim: Obesity has reached epidemic proportions, being defined by WHO as the "21st Century World Epidemic"(1) and the therapeutic solutions to treat this pandemic clearly scarce. Recently, the carotid body (CB), a chemoreceptor organ classically defined as an oxygen sensor, has been shown to be involved in metabolic deregulation. It was demonstrated that an overactivation of the CB is present in animal models of prediabetes and type 2 diabetes and that the abolishment of CB activity, through the resection of the carotid sinus nerve (CSN) prevents and reverses insulin resistance and glucose intolerance (2,3), an effect mainly due to the restore of glucose uptake by the adipose tissue (3). Also, we have shown that CSN resection decreased weight gain and total body fat mass and increased the amount of brown adipose tissue (BAT) in rats submitted to a high-fat diet (4). Taking this into account, the main goal of this work was to investigate if the effect of CSN on weight gain and metabolic function in obesity is due to an increase in BAT amount and function. Materials and Methods: Experiments have been performed in male Wistar rats randomly divided into 2 groups and submitted to 10 weeks of hypercaloric (HF, 5.1Kcal/g) or control (CTL, 2.56Kcal/g) diet. After 10 weeks of diet, animals were submitted to either bilateral CSN ablation or to a sham surgery. After CSN surgery, animals were maintained on their respective diets for 9 weeks and at the end of which they were anesthetized with pentobarbital (60 mg/kg i.p.) and tissues were collected, weighed and stored for further analysis. Caloric intake and body weight were monitored throughout the experiments. The number of mitochondrias and their activity were investigated in BAT by the use of Mitotracker and by UCP1 expression through immunohistochemistry. The expression of proteins involved in insulin signalling pathways, tissue hypoxia factors and inflammation was evaluated by Western blot. In a parallel experiment using the same animal model of obesity, in vivo glucose uptake was evaluated by an intravenous glucose tolerance test (IVGTT). Results: HF diet decreased insulin receptor (IR) expression by 68% and increase IL-1 and IL-6 expression by 30% and by 179% in BAT. Bilateral CSN resection increases IR expression in BAT by 68% and by 157% in control and HF animals, respectively and decreased significantly the inflammation markers, IL-1 and IL-6 by 57% and 47%, respectively. Moreover, CSN resection improved glucose uptake in BAT by 125% in control animal and by 67% in HF animals. Conclusion: We can conclude that CSN denervation positively impacts weight gain and metabolic function in a hypercaloric obese animal model via an improvement of BAT function and glucose uptake and a reduction in BAT inflammation.

Where applicable, experiments conform with Society ethical requirements