Long-Term Hypercaloric Diet Consumption Exacerbates Age-Induced Dysmetabolism and Carotid Body Dysfunction: Beneficial Effects of CSN Denervation

Abstract

Carotid bodies (CBs) are metabolic sensors whose dysfunction is involved in the genesis of dysmetabolic states. Ageing induces significant alterations in CB function also prompting to metabolic deregulation. On the other hand, metabolic disease can accelerate ageing processes. Taking these into account, we evaluated the effect of long-term hypercaloric diet intake and CSN resection on age-induced dysmetabolism and CB function. Experiments were performed in male Wistar rats subjected to 14 or 44 weeks of high-fat high-sucrose (HFHSu) or normal chow (NC) diet and subjected to either carotid sinus nerve (CSN) resection or a sham procedure. After surgery, the animals were kept on a diet for more than 9 weeks. Metabolic parameters, basal ventilation, and hypoxic and hypercapnic ventilatory responses were evaluated. CB type I and type II cells, HIF-1α and insulin receptor (IR), and GLP-1 receptor (GLP1-R)-positive staining were analyzed by immunofluorescence. Ageing decreased by 61% insulin sensitivity in NC animals, without altering glucose tolerance. Short-term and long-term HFHSu intake decreased insulin sensitivity by 55 and 62% and glucose tolerance by 8 and 29%, respectively. CSN resection restored insulin sensitivity and glucose tolerance. Ageing decreased spontaneous ventilation, but short-term or long-term intake of HFHSu diet and CSN resection did not modify basal ventilatory parameters. HFHSu diet increased hypoxic ventilatory responses in young and adult animals, effects attenuated by CSN resection. Ageing, hypercaloric diet, and CSN resection did not change hypercapnic ventilatory responses. Adult animals showed decreased type I cells and IR and GLP-1R staining without altering the number of type II cells and HIF-1α. HFHSu diet increased the number of type I and II cells and IR in young animals without significantly changing these values in adult animals. CSN resection restored the number of type I cells in HFHSu animals and decreased IR-positive staining in all the groups of animals, without altering type II cells, HIF-1α, or GLP-1R staining. In conclusion, long-term hypercaloric diet consumption exacerbates age-induced dysmetabolism, and both short- and long-term hypercaloric diet intakes promote significant alterations in CB function. CSN resection ameliorates these effects. We suggest that modulation of CB activity is beneficial in exacerbated stages of dysmetabolism.

Circulating Dopamine Is Regulated by Dietary Glucose and Controls Glucagon-like 1 Peptide Action in White Adipose Tissue

“…The observed plasma dopamine peak (around 1.5 nmol/L) is consistent with Maffei et al report using mixed meal-gavage Sprague-Dawley rats [6]. Intriguingly, higher doses of glucose (supraphysiologic)-200 mg/kg and 500 Peripheral dopamine has a role in blood pressure, gastrointestinal motility, glucose homeostasis, and body weight control [3,[13][14][15]. Initially thought to be exclusively produced at the level of the sympathetic nerves, pancreas, or adrenal medulla, dopamine in peripheral circulation is nowadays also acknowledged to be secreted by the gut [2,10,13].…”

Acute effects of insulin and insulin‐induced hypoglycaemia on carotid body chemoreceptor activity and cardiorespiratory responses in dogs

“…Intracarotid administration of NaCN produced an immediate and transient increase in whereas insulin‐mediated increase in was delayed (2–5 min) but sustained, reaching maximum response at 15–20 min, suggesting two independent mechanisms to drive ventilation in dog. A similar time profile for insulin‐mediated increase in was observed in rodents with intracarotid administration, which is in accordance with the time scale necessary for the activation of tyrosine kinase receptors, namely, the insulin receptors (Ribeiro et al., 2013 ; Melo et al., 2022 ). On the other hand, NaCN acts by inhibiting cytochrome oxidase in the type‐1 glomus cells in the carotid body to elicit the ventilatory response (Wang et al., 2017 ).…”

Overnutrition during Pregnancy and Lactation Induces Gender-Dependent Dysmetabolism in the Offspring Accompanied by Heightened Stress and Anxiety

“…By PD60, the male offspring, irrespective of maternal diet, displayed a significant increase in the area under the curve of the ipITT. This effect at PD60 suggests that the effects of age on insulin sensitivity that are clearly described in adulthood are already seen at early ages [ 37 ]. Regarding the female offspring, a different pattern emerged.…”

“…These dynamic changes suggest a time-dependent modulation of insulin sensitivity in females. Hormonal fluctuations, metabolic adaptation, or other sex-specific factors may contribute to these variations in insulin sensitivity during different developmental stages [ 37 ]. Moreover, the absence of effects of maternal dysmetabolism on insulin sensitivity with development contrasts with the documented impact of maternal obesity on insulin resistance later in life in animals [ 38 ] and humans [ 39 ].…”