The nicotinic acetylcholine receptor α7 in subcutaneous mature adipocytes: downregulation in human obesity and modulation by diet-induced weight loss

BACKGROUND: It is known that cholinergic anti-inflammatory reflex regulates inflammation in peripheral tissues. Nicotinic acetylcholine receptors (nAChRs) are mediators of this anti-inflammatory pathway and also non-neuronal cells express functional nAChrs. A role for alpha 7-subtype acetylcholine cholinergic receptor (alpha 7nAChR) in insulin sensitivity improvement has already been shown in rodents both in vivo and in vitro. However, no data are available on alpha 7nAChR expression in human adipocytes. OBJECTIVE: To investigate the expression and protein content of alpha 7nAChR in human subcutaneous adipose tissue (SAT) and in isolated mature adipocytes. DESIGN: A total of 39 SAT biopsy specimens obtained from obese and normal-weight subjects were used to assess alpha 7nAChR messenger RNA levels and to stimulate alpha 7nAChR with a specific agonist and antagonist in vitro. Additional SATs from eight non-diabetic obese subjects were also studied, before and after a 3-month lifestyle intervention. RESULTS: alpha 7nAChR expression was significantly lower in the SAT of obese subjects compared with that of normal-weight subjects. In mature adipocytes isolated from morbidly obese subjects (body mass index > 40 kgm(2)), alpha 7nAChR expression was 75% lower compared with adipocytes from normal-weight subjects. In adipocytes of obese subjects, alpha 7nAChR was downregulated also at protein level. In eight non-diabetic obese subjects, a lifestyle intervention (3 months of diet and physical activity) induced a significant weight loss and an increase in alpha 7nAChR SAT expression. In vitro stimulation of adipocytes with the specific alpha 7nAChR agonist PNU282987 induced a significant anti-inflammatory effect. Furthermore, a similar downregulation of the inflammatory profile, associated with a significant increase in alpha 7nAChR protein level, was observed after genistein stimulation. CONCLUSIONS: These results provide evidence that alpha 7nAChR expression levels are significantly decreased in obese subjects, and that this receptor modulates inflammatory gene expression in human adipocytes. The upregulation of alpha 7nAChR by genistein stimulation opens new insights for the management of low-grade inflammation linked to human obesity. International Journal of Obesity (2012) 36, 1552-1557; doi:10.1038/ijo.2011.275; published online 24 January 2012