experimental-approach-to-examine-leptin-signaling-carotid-bodies-its

Experimental Approach to Examine Leptin Signaling in the Carotid Bodies and its Effects on Control of Breathing

An adipocyte-produced hormone leptin is a potent respiratory stimulant, which may play an important role in defending respiratory function in obesity. The ...

Hospital Universitario Virgen del Rocío/Universidad de Sevilla

Non-invasive ventilation in amyotrophic lateral sclerosis in outpatients and inpatients. Different perspectives?

Gamma glutamyl transferase in 1744 patients with obstructive sleep apnea.

Obesity leads to sleep-disordered breathing (SDB) manifested by recurrent upper airway obstructions termed obstructive sleep apnea (OSA) and carbon dioxide retention due to hypoventilation. The objective of this work was to characterize breathing during sleep in C57BL6/J mice with diet-induced obesity (DIO). Arterial blood gas was measured in nine obese and nine lean mice during wakefulness. Nine male mice with DIO and six lean male C57BL/6J mice were head mounted with electroencephalogram (EEG) and electromyogram (EMG) electrodes. Sleep recordings were performed in the whole body plethysmography chamber; upper airway obstruction was characterized by the presence of inspiratory flow limitation in which airflow plateaus with increases in inspiratory effort. Obese mice showed significantly lower pH and higher partial pressure of arterial CO2 (PaCO2) in arterial blood gas compared to lean mice, 7.35 ± 0.04 versus 7.46 ± 0.06 (p < 0.001) and 38 ± 8 mm Hg versus 30 ± 5 mm Hg (p < 0.001). Obese mice had similar levels of minute ventilation to lean mice during sleep and wakefulness, despite higher body weight and temperature, indicating an increase in the metabolic rate and hypoventilation. Obese mice also showed baseline hypoxemia with decreased mean oxyhemoglobin saturation across sleep/wake states. Obese mice had a higher prevalence of flow-limited breathing compared to lean mice during sleep. However, the oxygen desaturation index in lean and obese mice did not differ. We conclude that DIO in mice leads to hypoventilation. Obesity also increases the frequency of inspiratory limited breaths, but it does not translate into progression of OSA.

Sleep-disordered breathing in C57BL/6J mice with diet-induced obesity.

Leptin is a potent respiratory stimulant. A long functional isoform of leptin receptor, LepR , was detected in the carotid body (CB), a key peripheral hypoxia sensor. However, the effect of leptin on minute ventilation (V ) and the hypoxic ventilatory response (HVR) has not been sufficiently studied. We report that LepR is present in approximately 74% of the CB glomus cells. Leptin increased carotid sinus nerve activity at baseline and in response to hypoxia in vivo. Subcutaneous infusion of leptin increased V and HVR in C57BL/6J mice and this effect was abolished by CB denervation. Expression of LepR in the carotid bodies of LepR deficient obese db/db mice increased V during wakefulness and sleep and augmented the HVR. We conclude that leptin acts on LepR in the CBs to stimulate breathing and HVR, which may protect against sleep disordered breathing in obesity.

Leptin acts in the carotid bodies to increase minute ventilation during wakefulness and sleep and augment the hypoxic ventilatory response.

Vascular damage must be diagnosed early in patients with hypertension. In this regard, endothelial dysfunction (ED) is an early sign of vascular disease and a predictor of cardiovascular diseases. In obstructive sleep apnea (OSA), intermittent hypoxia triggers ED, but mechanisms are not clear. In this context, it has been described that BK channels regulates arterial tone and that chronic and intermittent hypoxia downregulates the expression of the BK channel β1-subunit facilitating vasoconstriction. Thus, we investigated the relationship among hypoxemia, ED, and mRNA expression of the β1-subunit in patients with severe OSA. We aimed to assess (1) ED in non-hypertensive patients with OSA using laser-Doppler flowmetry, (2) BK β1-subunit mRNA expression, and (3) the impact of continuous positive airway pressure (CPAP) treatment on ED and β1-subunit regulation.

Article	Year
Non-invasive ventilation in amyotrophic lateral sclerosis in outpatients and inpatients. Different perspectives? Archivos de bronconeumologia\| PubMed ID: 25446872	2016
Gamma glutamyl transferase in 1744 patients with obstructive sleep apnea. Sleep & breathing = Schlaf & Atmung\| PubMed ID: 26156888	2016
Sleep-disordered breathing in C57BL/6J mice with diet-induced obesity. Sleep\| PubMed ID: 29767787	2018
Leptin acts in the carotid bodies to increase minute ventilation during wakefulness and sleep and augment the hypoxic ventilatory response. The Journal of physiology\| PubMed ID: 30285278	2019
Relationship between the endothelial dysfunction and the expression of the β1-subunit of BK channels in a non-hypertensive sleep apnea group. PloS one\| PubMed ID: 31216297	2019

Candela Caballero-Eraso

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