RESUMEN
OBJECTIVES: Heat-sensory neurons from the dorsal root ganglia (DRG) play a pivotal role in detecting the cutaneous temperature and transmission of external signals to the brain, ensuring the maintenance of thermoregulation. However, whether these thermoreceptor neurons contribute to adaptive thermogenesis remains elusive. It is also unknown whether these neurons play a role in obesity and energy metabolism. METHODS: We used genetic ablation of heat-sensing neurons expressing calcitonin gene-related peptide α (CGRPα) to assess whole-body energy expenditure, weight gain, glucose tolerance, and insulin sensitivity in normal chow and high-fat diet-fed mice. Exvivo lipolysis and transcriptional characterization were combined with adipose tissue-clearing methods to visualize and probe the role of sensory nerves in adipose tissue. Adaptive thermogenesis was explored using infrared imaging of intrascapular brown adipose tissue (iBAT), tail, and core temperature upon various stimuli including diet, external temperature, and the cooling agent icilin. RESULTS: In this report, we show that genetic ablation of heat-sensing CGRPα neurons promotes resistance to weight gain upon high-fat diet (HFD) feeding and increases energy expenditure in mice. Mechanistically, we found that loss of CGRPα-expressing sensory neurons was associated with reduced lipid deposition in adipose tissue, enhanced expression of fatty acid oxidation genes, higher exvivo lipolysis in primary white adipocytes, and increased mitochondrial respiration from iBAT. Remarkably, mice lacking CGRPα sensory neurons manifested increased tail cutaneous vasoconstriction at room temperature. This exacerbated cold perception was not associated with reduced core temperature, suggesting that heat production and heat conservation mechanisms were engaged. Specific denervation of CGRPα neurons in intrascapular BAT did not contribute to the increased metabolic rate observed upon global sensory denervation. CONCLUSIONS: Taken together, these findings highlight an important role of cutaneous thermoreceptors in regulating energy metabolism by triggering counter-regulatory responses involving energy dissipation processes including lipid fuel utilization and cutaneous vasodilation.
Asunto(s)
Péptido Relacionado con Gen de Calcitonina/genética , Péptido Relacionado con Gen de Calcitonina/metabolismo , Obesidad/metabolismo , Células Receptoras Sensoriales/metabolismo , Termogénesis/genética , Termogénesis/fisiología , Tejido Adiposo Pardo/metabolismo , Tejido Adiposo Pardo/patología , Tejido Adiposo Blanco/metabolismo , Tejido Adiposo Blanco/patología , Animales , Regulación de la Temperatura Corporal/genética , Regulación de la Temperatura Corporal/fisiología , Frío , Dieta Alta en Grasa/efectos adversos , Metabolismo Energético/genética , Metabolismo Energético/fisiología , Femenino , Resistencia a la Insulina , Lipólisis/genética , Lipólisis/fisiología , Masculino , Ratones , NeuronasRESUMEN
Acute kidney injury is a complication of open-heart surgery that carries a poor prognosis. Studies have shown that postoperative renal function deterioration in cardiovascular surgery patients increases in-hospital mortality and adversely affects long-term survival. Identifying individuals at risk for developing AKI and aggressive early intervention is extremely important to optimize outcomes. This paper provides an overview of the etiology, prognostic markers, risk factors, and prevention of AKI and treatments that may favorably affect outcomes.
Asunto(s)
Lesión Renal Aguda/etiología , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Lesión Renal Aguda/epidemiología , Salud Global , Cardiopatías/cirugía , Mortalidad Hospitalaria/tendencias , Humanos , Incidencia , Complicaciones PosoperatoriasRESUMEN
The risk of developing CVD is high among CKD patients and, as a result, cardiovascular-related complications account for high morbidity and mortality. Multiple factors contribute to CVD in CKD patients, including hypertension, anemia, inflammation, hyperlipidemia, calcium-phosphorus-parathyroid hormone imbalance, and hyperuricemia. Each one of these complications needs to be identified and treated in an attempt to improve survival. Early markers of CVD such as microalbuminuria and uric acid levels need to be added to the routine annual evaluation, particularly among high-risk individuals such as diabetics, hypertensives, smokers, and the elderly. Likewise, the use of eGFR is highly recommended as a screening tool in those individuals.