Abstract
Background: Little is known about the effects of hypoxia on scavenger receptors (SRs) levels in adipocytes. We analyzed the effect of morbid obesity and hypoxia on SRs and inflammation markers in human visceral adipocytes and whether ox-LDL modify the inflammatory profile produced by hypoxia. Methods: We studied in 17 non-obese and 20 subjects with morbid obesity (MO) the mRNA expression of HIF-1α, SRs (LOX-1, MSR1, CL-P1 and CXCL16), IL6 and TNFα in visceral adipocytes and the effect of hypoxia with or without ox-LDL on visceral in vitro-differentiated adipocytes (VDA). Results: HIF-1α, TNFα, IL6, LOX-1, MSR1 and CXCL16 expression in adipocytes was increased in MO when compared with those in non-obese subjects (p < 0.05). The expression of most of the inflammatory markers and SRs gene correlated with HIF-1α. In VDA, hypoxia increased TNFα, IL6, MSR1, CXCL16 and CL-P1 (p < 0.05) in non-obese subjects, and TNFα, IL6, MSR1 and CXCL16 (p < 0.05) in MO. Silencing HIF-1α prevented the increase of TNFα, IL6, LOX-1, MSR1, CL-P1 and CXCL16 expression (p < 0.05). The combination of hypoxia and ox-LDL produced higher TNFα expression (p = 0.041). Conclusions: Morbid obesity and hypoxia increased SRs and inflammatory markers in visceral adipocytes. In a hypoxic state, ox-LDL increased the proinflammatory response of visceral adipocytes to hypoxia.
Highlights
Obesity is associated with an increase of adipose tissue hypoxia [1,2]
The aims of this study were to analyze in human visceral adipocytes (a) whether morbid obesity modified scavenger receptors (SRs) expression, (b) whether hypoxia could produce an increase of SRs expression, as we had previously demonstrated for oxidized low-density lipoproteins (ox-LDL) [18], (c) the effect of hypoxia on inflammation markers and (d) whether ox-LDL could increase the inflammatory response produced by hypoxia
We suggest that visceral adipocytes from patients with morbid obesity are in hypoxia and that these cells could participate in the upregulation of the inflammation found in the hypoxia state
Summary
Obesity is associated with an increase of adipose tissue hypoxia [1,2]. Biomedicines 2021, 9, 1715 of hypoxia-inducible factor 1-α (HIF-1α) [4]. HIF-1α modulates the function of phagocytic cells, mainly macrophages, by stimulating surface receptors such as scavenger receptors (SRs) for oxidized low-density lipoproteins (ox-LDL) [8]. A previous study showed that hypoxia reoxygenation of cardiomyocytes induces lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), a type of SR [9]. The mRNA expression of HIF-1α, SRs (LOX-1, MSR1, CL-P1 and CXCL16), IL6 and TNFα in visceral adipocytes and the effect of hypoxia with or without ox-LDL on visceral in vitro-differentiated adipocytes (VDA). Results: HIF-1α, TNFα, IL6, LOX-1, MSR1 and CXCL16 expression in adipocytes was increased in MO when compared with those in non-obese subjects (p < 0.05).
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