Oxygenation of adipose tissue: A human perspective

Abstract

Obesity is a complex disorder of excessive adiposity, and is associated with adverse health effects such as cardiometabolic complications, which are to a large extent attributable to dysfunctional white adipose tissue. Adipose tissue dysfunction is characterized by adipocyte hypertrophy, impaired adipokine secretion, a chronic low‐grade inflammatory status, hormonal resistance and altered metabolic responses, together contributing to insulin resistance and related chronic diseases. Adipose tissue hypoxia, defined as a relative oxygen deficit, in obesity has been proposed as a potential contributor to adipose tissue dysfunction, but studies in humans have yielded conflicting results. Here, we will review the role of adipose tissue oxygenation in the pathophysiology of obesity‐related complications, with a specific focus on human studies. We will provide an overview of the determinants of adipose tissue oxygenation, as well as the role of adipose tissue oxygenation in glucose homeostasis, lipid metabolism and inflammation. Finally, we will discuss the putative effects of physiological and experimental hypoxia on adipose tissue biology and whole‐body metabolism in humans. We conclude that several lines of evidence suggest that alteration of adipose tissue oxygenation may impact metabolic homeostasis, thereby providing a novel strategy to combat chronic metabolic diseases in obese humans.

<p>Low Elevation and Physical Inactivity are Associated with a Higher Prevalence of Metabolic Syndrome in Ecuadorian Adults: A National Cross-Sectional Study</p>

“…14 People living at high elevation, above 2500 masl, display a fall in arterial oxygen saturation and present physiological adaptations to this environmental pressure. 16,31 These two responses produce an increase in hemoglobin concentrations, enlarged lung volume and increased ventilatory response. 15,33 In this case, the highest regions of the world demonstrate the biological human adaptation to low oxygen concentrations (hypoxia), including the Ethiopian Siemen Mountains, the Tibetan Himalayan valleys, and the Andean Altiplano in South America.…”

“…11,15 It is also reported to increase glucose uptake and its tolerance, which reduces blood glucose levels. [16][17][18] Furthermore, living at high elevation is associated with severe hypoxia and a reduction in peripheral oxygen saturation leading to a decrease in insulin sensitivity, whereas mild hypoxia may improve insulin sensitivity. 17,19,20 Some studies have described an inverse association between elevation and lower obesity prevalence and incidence, [21][22][23][24] as well as lower diabetes 3,25 and hypertension proportions.…”

Nutrition, dietary habits, and weight management to prevent and treat patients with peripheral artery disease

“…Weight status constitutes a significant role in the progression of atherosclerotic disease (Neeland et al, 2019). Overweight status and obesity are characterised by excessive expansion of white adipose tissue (WAT) mass (Lempesis et al, 2020). The pathophysiology of obesity and its complications, however, is not only driven by the increase in WAT mass, but mainly by the dysfunctional status of the organ, also known as adiposopathy (Blüher, 2013;Goossens, 2008Goossens, , 2017Goossens and Blaak, 2015;Lempesis et al, 2020).…”

Increased Insulin Sensitivity by High-Altitude Hypoxia in Mice with High-Fat Diet-Induced Obesity Is Associated with Activated AMPK Signaling and Subsequently Enhanced Mitochondrial Biogenesis in Skeletal Muscles

“…Moderate intermittent hypoxia for 4 weeks (12 h, 14% O 2 , 7 days/week) improves glucose tolerance and increases GLUT4 levels in rats [15]. Prolonged exposure (14 days) to low (5% O 2 ) pO 2 levels tended to increase basal glucose uptake in differentiated human multipotent adipose-derived stem cells [16]. Although these seemingly contradictory effects of hypoxia highlight the important and complicated role of hypoxia on energy balance and metabolism, little is known about the key molecules and signaling pathways that contribute to the relationship between insulin resistance and high-altitude induced ambient hypoxia.…”