Hypoxia-induced metabolic dysfunction in WAT

Background: Excessive white adipose tissue (WAT) expansion as in obesity is generally associated with chronic inflammation of WAT, which contributes to obesity associated complications. Low oxygen availability in WAT is hypothesized to be the initiator of this inflammatory response. Hypothesis: We examined the hypothesis that local tissue hypoxia is responsible for the initiation of inflammation in WAT. Research design and methods: Diet-induced obese male C57BL/6JOlaHsd mice, housed at thermoneutrality, were exposed to mild environmental oxygen restriction (OxR, to 13% oxygen) for five days and compared with mice kept at normoxia, after which WAT and serum were collected. Body composition, systemic metabolic parameters, WAT macrophage infiltration (as marker for tissue inflammation) and whole genome microarray analysis, and circulating adipokines were measured. Results: Five days OxR decreased body weight and fat mass, and increased blood levels of haemoglobin and haematocrit, as well as lactate to glucose ratio, which indicated systemic hypoxia. No difference in adipose tissue inflammation was found, which was supported by down regulation of inflammation-associated transcript levels of S100a8, Saa1, and Saa3. Serum metabolomics revealed an increase of branched chain amino acid Valine and propionylcarnitine. Adipokines CCDC3, CCK, and Adiponectin are reduced by OxR on transcript (Cck) or serum protein level (Adiponectin), or both (CCDC3). Conclusions: Mild oxygen restriction does not increase white adipose tissue inflammation in obese mice. However, a systemic adaptation together with a metabolic response in WAT was observe