Physiological Responses to Hypoxia on Triglyceride Levels

Abstract

Hypoxia is a condition during which the body or specific tissues are deprived of oxygen. This phenomenon can occur in response to exposure to hypoxic environmental conditions such as high-altitude, or because of pathophysiological conditions such as obstructive sleep apnea. Circumstances such as these can restrict supply or increase consumption of oxygen, leading to oxyhemoglobin desaturation and tissue hypoxia. In certain cases, hypoxia may lead to severe health consequences such as an increased risk of developing cardiovascular diseases and type 2 diabetes. A potential explanation for the link between hypoxia and an increased risk of developing cardiovascular diseases lies in the disturbing effect of hypoxia on circulating blood lipids, specifically its capacity to increase plasma triglyceride concentrations. Increased circulating triglyceride levels result from the production of triglyceride-rich lipoproteins, such as very-low-density lipoproteins and chylomicrons, exceeding their clearance rate. Considerable research in murine models reports that hypoxia may have detrimental effects on several aspects of triglyceride metabolism. However, in humans, the mechanisms underlying the disturbing effect of hypoxia on triglyceride levels remain unclear. In this mini-review, we outline the available evidence on the physiological responses to hypoxia and their impact on circulating triglyceride levels. We also discuss mechanisms by which hypoxia affects various organs involved in the metabolism of triglyceride-rich lipoproteins. This information will benefit scientists and clinicians interested in the mechanistic of the regulatory cascade responsible for the response to hypoxia and how this response could lead to a deteriorated lipid profile and an increased risk of developing hypoxia-related health consequences.

Comprehensive lipidomic analysis reveals regulation of glyceride metabolism in rat visceral adipose tissue by high-altitude chronic hypoxia

“…A study have showeded increased sympathetic activation and up-regulation lipolysis under hypoxia exposure [27]. Consistent with this hypoxia exposure for 14 days in mice significantly increased adipocyte lipolysis and elevated NEFA levels [1]. Several studies have also demonstrated that reduced oxygen supply in the air could increase adipocyte lipolysis both in vivo and in vitro [28][29][30][31][32].…”

“…TGs, which are composed of 3 fatty acids and 1 glycerol molecule, represent the most energy-dense lipolysis substrate [1]. In addition to adipocytes, almost all types of cells have the ability to store excess energy in the form of TGs in lipid droplets [34].…”

“…Hypoxia is a condition in which the body or specific tissues are deprived of oxygen [1]. This phenomenon can occur upon exposure to hypoxic environmental conditions, such as high altitude [2].…”

“…Among glycerides, diacylglycerols (DGs) and triacylglycerols (TGs) are the main types of glycerol [11]. However, hypoxia may disturb the balance of lipid storage and lipid mobilization in adipose tissue [1]. In particular, hypoxia induces decreased lipoprotein lipase activity in adipocytes [8,12] and has been shown to stimulate lipolysis of visceral adipocytes [13].…”

Effects of Intermittent Normobaric Hypoxia on Health-Related Outcomes in Healthy Older Adults: A Systematic Review

“…Currently, some review studies have proposed exposure to hypoxic conditions, either passive or active in combination with exercise, as a promising tool to achieve health benefits [5][6][7][8], targeting hypoxia-inducible factor (HIF) and its signaling pathway as a novel therapeutic option to deal with various chronic diseases [9,10]. On the one hand, an oxygen-deprived (hypoxia) environment impairs cell adaptation and survival [11] with chronic exposure to severe hypoxia leading to hypoxemia and cardiovascular and pulmonary complications [12,13]. On the other hand, intermittent hypoxia (IH) has been shown to exert beneficial effects at the cardiovascular, metabolic, and cognitive levels, both in healthy and pathological individuals [14][15][16].…”