Chronic intermittent hypoxia induced greater insulin resistance (P<0.001) and preferential whitening of visceral white adipose tissue compared to sustained hypoxia or room air in mice.
Does chronic intermittent and sustained hypoxia alter visceral white adipose tissue characteristics and insulin resistance in eight-week-old male C57BL/6J mice?
Intermittent hypoxia induces whitening of visceral adipose tissue and insulin resistance, unlike sustained hypoxia which promotes browning, providing mechanistic insights into metabolic dysfunction in conditions like sleep apnea.
valor p: p=<0.001
Angiogenesis, a process induced by hypoxia in visceral white adipose tissues (vWAT) in the context of obesity, mediates obesity-induced metabolic dysfunction and insulin resistance. Chronic intermittent hypoxia (IH) and sustained hypoxia (SH) induce body weight reductions and insulin resistance of different magnitudes, suggesting different hypoxia inducible factor (HIF)-1α-related activity. Eight-week-old male C57BL/6J mice (n = 10-12/group) were exposed to either IH, SH, or room air (RA). vWAT were analyzed for insulin sensitivity (phosphorylated (pAKT)/AKT), HIF-1α transcription using chromatin immunoprecipitation (ChIP)-sequencing, angiogenesis using immunohistochemistry, and gene expression of different fat cell markers and HIF-1α gene targets using quantitative polymerase chain reaction or microarrays. Body and vWAT weights were reduced in hypoxia (SH > IH > RA; P > > SH = RA; P < 0.001). IH induces preferential whitening of vWAT, as opposed to prominent browning in SH. Unlike SH, IH elicits early HIF-1α activity that is unsustained over time and is accompanied by concurrent vascular rarefaction, inflammation, and insulin resistance. Thus, the dichotomous changes in HIF-1α transcriptional activity and brown/beige/white fat balance in IH and SH should enable exploration of mechanisms by which altered sympathetic outflow, such as that which occurs in apneic patients, results in whitening, rather than the anticipated browning of adipose tissues that occurs in SH.
Gozal et al. (Wed,) conducted a other in Hypoxia-induced metabolic dysfunction. Chronic intermittent hypoxia and sustained hypoxia vs. Room air was evaluated on Insulin resistance and body/vWAT weights (p=<0.001). Chronic intermittent hypoxia induced greater insulin resistance (P<0.001) and preferential whitening of visceral white adipose tissue compared to sustained hypoxia or room air in mice.