Melo Bernardete F, Sacramento Joana F, Capucho Adriana M, Sampaio-Pires Dinis, Prego Cláudia S, Conde Silvia V
CEDOC, CEDOC, NOVA Medical School, NMS, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisboa, Portugal.
Front Physiol. 2022 May 4;13:889660. doi: 10.3389/fphys.2022.889660. eCollection 2022.
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.
颈动脉体（CBs）是代谢传感器，其功能障碍与代谢紊乱状态的发生有关。衰老会引起CB功能的显著改变，也会促使代谢失调。另一方面，代谢疾病会加速衰老过程。考虑到这些因素，我们评估了长期高热量饮食摄入和切除颈动脉窦神经（CSN）对衰老引起的代谢紊乱和CB功能的影响。实验在雄性Wistar大鼠中进行，这些大鼠接受14周或44周的高脂肪高蔗糖（HFHSu）或正常饲料（NC）饮食，并接受颈动脉窦神经切除或假手术。手术后，动物继续进食超过9周。评估了代谢参数、基础通气以及低氧和高碳酸血症通气反应。通过免疫荧光分析了CB I型和II型细胞、缺氧诱导因子-1α（HIF-1α）、胰岛素受体（IR）以及胰高血糖素样肽-1受体（GLP-1R）的阳性染色。衰老使NC组动物的胰岛素敏感性降低了61%，而葡萄糖耐量未改变。短期和长期摄入HFHSu分别使胰岛素敏感性降低了55%和62%，葡萄糖耐量降低了8%和29%。切除CSN可恢复胰岛素敏感性和葡萄糖耐量。衰老降低了自主通气，但短期或长期摄入HFHSu饮食以及切除CSN并未改变基础通气参数。HFHSu饮食增加了幼年和成年动物的低氧通气反应，而CSN切除减弱了这种作用。衰老、高热量饮食和切除CSN均未改变高碳酸血症通气反应。成年动物的I型细胞数量以及IR和GLP-1R染色减少，而II型细胞数量和HIF-1α未改变。HFHSu饮食增加了幼年动物I型和II型细胞数量以及IR，但成年动物的这些值无显著变化。切除CSN可恢复HFHSu组动物的I型细胞数量，并减少所有组动物的IR阳性染色，而II型细胞、HIF-1α或GLP-1R染色未改变。总之，长期高热量饮食会加剧衰老引起的代谢紊乱，短期和长期摄入高热量饮食均会导致CB功能的显著改变。切除CSN可改善这些影响。我们认为，调节CB活性在代谢紊乱的加重阶段有益。
