Involvement of overweight and lipid metabolism in the development of pulmonary hypertension under conditions of chronic intermittent hypoxia

Abstract

There is growing evidence that exposure to hypoxia, regardless of the source, elicits several metabolic responses in individuals. These responses are constitutive and are usually observed under hypoxia but vary according to the type of exposure. The aim of this review was to describe the involvement of obesity and lipid metabolism in the development of high-altitude pulmonary hypertension and in the development of acute mountain sickness under chronic intermittent hypoxia. Overweight or obesity, which are common in individuals with long-term chronic intermittent hypoxia exposure (high-altitude miners, shift workers, and soldiers), are thought to play a major role in the development of acute mountain sickness and high-altitude pulmonary hypertension. This association may be rooted in the interactions between obesity-related metabolic and physical alterations, such as increased waist circumference and neck circumference, among others, which lead to critical ventilation impairments; these impairments aggravate hypoxemia at high altitude, thereby triggering high-altitude diseases. Overweight and obesity are strongly associated with higher mean pulmonary artery pressure in the context of long-term chronic intermittent hypoxia. Remarkably, de novo synthesis of triglycerides by the sterol regulatory element-binding protein-1c pathway has been demonstrated, mainly due to the upregulation of stearoyl-CoA desaturase-1, which is also associated with the same outcomes. Therefore, overweight, obesity, and other metabolic conditions may hinder proper acclimatization. The involved mechanisms include respiratory impairment, alteration of the nitric oxide pathways, inflammatory status, reactive oxygen species imbalance, and other metabolic changes; however, further studies are required.

TMT-Based Plasma Proteomics Reveals Dyslipidemia Among Lowlanders During Prolonged Stay at High Altitudes

“…We also observed a moderate correlation of diastolic blood pressure (DBP) with LDL (R-squared = 0.46, p = 0.04) for HA-D7 group. Persistent hypoxia at high altitude induces HIF-1α that upregulates stearoyl-CoA desaturase (SCD)-1 in the sterol regulatory element-binding protein (SREBP)-1c pathway resulting in increased hepatic de novo TGs synthesis (Siques et al, 2020). In contrast, we observed the lowest HDL levels for HA-D150.…”

Oxygen Supply System Management in an Overweight Adult after 12 Months in Antarctica—Study Case

“…Along with significant decrease in oxygen consumption at rest per 1 kg of body mass when the subject was overweight it can suggest the influence of the long-term chronic intermittent hypoxia. Siques P. et al [ 39 ] indicated that overweight and obesity impair the activity of adaptive mechanisms during the process of acclimatization in the mountains. According to San Martin R. et al [ 40 ] obesity, or being overweight, plays a major role in the development of the high-altitude illnesses (acute mountain sickness, hypoxic pulmonary hypertension, and chronic mountain sickness).…”

Hipertension pulmonar de altura

“…La gran altitud es definida convencionalmente por encima de 2500 m s. n. m. ó 8 250 pies; a partir de ese nivel, los niveles de saturación de oxígeno en la sangre arterial comienzan a caer en la mayoría de las personas (52) . La hipoxia hipobárica ocurre cuando al ascender a la altura existe menor presión barométrica (13) ; a pesar de que la concentración de oxigeno permanece igual (21%), existe disminución de la presión parcial de oxigeno inspirado (POi2) y de la saturación de hemoglobina arterial (Sat O 2 ) (13) . Se ha reportado que el ascenso a una altitud terrestre entre los 3 800 y 4 600 m s. n. m. se asocia con una elevación de la presión arterial pulmonar media de hasta 20-25 mmHg y la presión arterial pulmonar sistólica de hasta 30-40 mmHg (8) .…”

“…Según la duración de la exposición a la hipoxia existe la forma aguda, crónica e intermitente (11) , y la hipoxia hipobárica puede incrementar los niveles de estrés oxidativo ocasionando daño celular y generar varias enfermedades de altura (12) . Las principales enfermedades de altura que se presentan por desadaptación al entorno ambiental son: el mal agudo de montaña (MAM), el edema cerebral agudo de altura (ECAA), el edema pulmonar agudo de altura (EPAA), el mal subagudo de montaña (MSM), la hipertensión pulmonar de altura (HPA) y el mal de montaña crónico (MMC), las cuales se presentan de acuerdo al tiempo de exposición de la altura (13)(14)(15)(16) .…”