Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate school of Agriculture, Kyoto University, Uji, Kyoto, Japan.
Research Unit for Physiological Chemistry, The Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Japan.
Mol Nutr Food Res. 2017 Oct;61(10). doi: 10.1002/mnfr.201700064. Epub 2017 Jul 19.
Recent reports indicate that gut microbiota and their metabolites may regulate host inflammatory conditions, including the chronic inflammation of obese adipose tissues. In this study, we investigated whether specific synthesized fatty acids, identical to the metabolites generated by gut microbiota, act as anti-inflammatory factors in obesity-induced inflammation.
We first used lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages to examine the anti-inflammatory effect of fatty acids synthesized to resemble representative polyunsaturated fatty acid metabolites from gut microbiota. Fatty acids containing an enone structure showed the most potent anti-inflammatory activity. Enone fatty acids also displayed anti-inflammatory effects on macrophages cocultured with hypertrophied 3T3-L1 or immortalized primary adipocytes; and macrophages stimulated with 3T3-L1 adipocyte conditioned medium. Consistently, the beneficial outcome was revealed in the case of LPS- and obesity-induced inflammatory cytokine stimulation in ex vivo adipose tissues. Furthermore, these fatty acids recovered the suppression of β-adrenergic receptor-stimulated uncoupling protein 1 expression and secretion of adiponectin in C3H10T1/2 and 3T3-L1 adipocytes, respectively, under inflammatory conditions, suggesting that enone fatty acids can ameliorate dysfunctions of adipocytes induced by inflammation.
These findings indicate that synthesized enone fatty acids show potent anti-inflammatory effects, leading to the improvement of inflammation-induced dysfunctions in adipocytes.
最近的报告表明，肠道微生物群及其代谢产物可能调节宿主炎症状态，包括肥胖脂肪组织的慢性炎症。在这项研究中，我们研究了是否特定合成的脂肪酸，与肠道微生物群产生的代谢产物相同，作为肥胖引起的炎症中的抗炎因子。
我们首先使用脂多糖（LPS）刺激 RAW 264.7 巨噬细胞，以检查类似于肠道微生物群代表性多不饱和脂肪酸代谢物的脂肪酸的抗炎作用。含有烯酮结构的脂肪酸显示出最强的抗炎活性。烯酮脂肪酸对与肥大的 3T3-L1 或永生化原代脂肪细胞共培养的巨噬细胞以及用 3T3-L1 脂肪细胞条件培养基刺激的巨噬细胞也具有抗炎作用。一致的是，在 LPS 和肥胖诱导的炎症细胞因子刺激的离体脂肪组织中显示出了有益的结果。此外，这些脂肪酸恢复了在炎症条件下 C3H10T1/2 和 3T3-L1 脂肪细胞中β-肾上腺素能受体刺激解偶联蛋白 1 表达和脂联素分泌的抑制作用，表明烯酮脂肪酸可以改善炎症引起的脂肪细胞功能障碍。
这些发现表明，合成的烯酮脂肪酸具有很强的抗炎作用，可以改善炎症引起的脂肪细胞功能障碍。
