Mizuta Kentaro, Matoba Atsuko, Shibata Sumire, Masaki Eiji, Emala Charles W
Department of Dento-oral Anesthesiology, Tohoku University Graduate School of Dentistry, Sendai, Japan.
Department of Anesthesiology, College of Physicians and Surgeons of Columbia University, New York, New York, United States.
Jpn Dent Sci Rev. 2019 Nov;55(1):103-107. doi: 10.1016/j.jdsr.2019.07.002. Epub 2019 Aug 29.
Obesity is a major risk factor for the development of asthma, and worsens the key features of asthma including airway hyperresponsiveness, inflammation, and airway remodeling. Although pro- and anti-inflammatory adipocytokines may contribute to the pathogenesis of asthma in obesity, the mechanistic basis for the relationship between asthma and obesity remains unclear. In obese individuals, the increased amount of adipose tissue results in the release of more long-chain free fatty acids as compared to lean individuals, causing an elevation in plasma long-chain free fatty acid concentrations. Recent findings suggest that the free fatty acid receptor 1 (FFAR1), which is a sensor of medium- and long-chain free fatty acids, is expressed on airway smooth muscle and plays a pivotal role in airway contraction and airway smooth muscle cell proliferation. In contrast, FFAR4, which is a sensor for long-chain -3 polyunsaturated fatty acids and also expressed on airway smooth muscle, does not contribute to airway contraction and airway smooth muscle cell proliferation. Functional roles for short-chain fatty acid receptors FFAR2 and FFAR3 in the pathogenesis of asthma is still under debate. Taken together, adipose-derived long-chain free fatty acids may contribute to the pathogenesis of asthma in obesity through FFAR1.
肥胖是哮喘发病的主要危险因素，会加重哮喘的关键特征，包括气道高反应性、炎症和气道重塑。尽管促炎和抗炎脂肪细胞因子可能在肥胖相关哮喘的发病机制中起作用，但哮喘与肥胖之间关系的机制基础仍不清楚。与瘦人相比，肥胖个体的脂肪组织量增加，导致释放更多的长链游离脂肪酸，使血浆长链游离脂肪酸浓度升高。最近的研究结果表明，游离脂肪酸受体1（FFAR1）作为中链和长链游离脂肪酸的感受器，表达于气道平滑肌上，并在气道收缩和气道平滑肌细胞增殖中起关键作用。相比之下，游离脂肪酸受体4（FFAR4）作为长链-3多不饱和脂肪酸的感受器，也表达于气道平滑肌上，但对气道收缩和气道平滑肌细胞增殖没有影响。短链脂肪酸受体FFAR2和FFAR3在哮喘发病机制中的功能作用仍存在争议。综上所述，脂肪源性长链游离脂肪酸可能通过FFAR1在肥胖相关哮喘的发病机制中起作用。
