Visceral white fat remodelling contributes to intermittent hypoxia-induced atherogenesis.
Obstructive sleep apnoea is a highly prevalent disease characterised by repetitive upper airway collapse during sleep leading to intermittent hypoxia. Cardiometabolic complications of sleep apnoea have been mostly attributed to intermittent hypoxia. These consequences could be mediated through intermittent hypoxia-related alterations of the visceral white fat, as it is recognised for playing an important role in inflammation, atherogenesis and insulin resistance. Epididymal adipose tissue alterations were investigated in 20-week-old nonobese male apolipoprotein E-deficient mice exposed to intermittent hypoxia (inspiratory oxygen fraction 5-21%, 60-s cycle, 8 h · day(-1)) or air for 6 weeks. These adipose tissue alterations, as well as metabolic alterations and aortic atherosclerosis, were then assessed in lipectomised or sham-operated mice exposed to intermittent hypoxia or air for 6 weeks. Intermittent hypoxia induced morphological (shrunken adipocytes), functional (increased uncoupling protein-1 expression) and inflammatory (increased macrophage recruitment and secretion of interleukin-6 and tumour necrosis factor-α) remodelling of epididymal adipose tissue. Hypoxic mice presented more severe dyslipidaemia and atherosclerosis lesions and developed insulin resistance. Epididymal lipectomy attenuated both intermittent hypoxia-induced dyslipidaemia and atherogenesis, but did not improve insulin sensitivity. Our results confirmed that the dyslipidaemic and proatherogenic effects of intermittent hypoxia are partly mediated through morphological, functional and inflammatory remodelling of visceral white fat, regardless of obesity.
HP2 Laboratory, Grenoble.
Laureline
L
Poulain
Amandine
A
Thomas
Jennifer
J
Rieusset
Louis
L
Casteilla
Patrick
P
Levy
Claire
C
Arnaud
Maurice
M
Dematteis
D052436:Adipose Tissue, White / Q000473:pathology*; D000818:Animals; D001011:Aorta / Q000473:pathology; D050197:Atherosclerosis / Q000473:pathology*; D018932:Chemokine CCL2 / Q000378:metabolism; D005951:Glucose Tolerance Test; D000860:Hypoxia; D007249:Inflammation; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000473:pathology*; D007473:Ion Channels / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins / Q000378:metabolism; D000071256:Uncoupling Protein 1
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1