Although recognized as an important endocrine organ, little is known about the mechanisms through which adipose tissue can regulate inflammatory responses in distant tissues, such as lung, that are affected by obesity. To explore potential mechanisms, male C57BL/6J mice were provided either high-fat diet, low-fat diet, or were provided a high-fat diet then switched to the low-fat diet to promote weight loss. Visceral adipocytes were then cultured in vitro to generate conditioned media (CM) that was used to treat both primary (MTEC) and immortalized (MTCC) airway epithelial cells. Adiponectin levels were greatly depressed in the CM from both obese and diet-switched adipocytes relative to mice continually fed the low-fat diet. MTEC from obese mice secreted higher baseline levels of inflammatory cytokines than MTEC from lean or diet-switched mice. MTEC treated with obese adipocyte CM increased their secretion of these cytokines compared to MTEC treated with lean CM. Diet-switched CM modestly decreased the production of cytokines compared to obese CM, and these effects were recapitulated when the CM was used to treat MTCC. Adipose stromal vascular cells from obese mice expressed genes consistent with an M1 macrophage phenotype and decreased eosinophil abundance compared to lean SVF, a profile that persisted in the lean diet-switched mice despite substantial weight loss. Soluble factors secreted from obese adipocytes exert a pro-inflammatory effect on airway epithelial cells, and these alterations are attenuated by diet-induced weight loss, which could have implications for the airway dysfunction related to obese asthma and its mitigation by weight loss.
Endospanin 1 silencing in the hypothalamic arcuate nucleus contributes to sustained weight loss of high fat diet obese mice