Ha-Eun Yang1, Yongjia Li1, Akira Nishimura1, Huei-Fen Jheng1, Ana Yuliana1, Ryuji Kitano-Ohue1,2, Wataru Nomura1,2, Nobuyuki Takahashi1,2, Chu-Sook Kim3, Rina Yu3, Nahoko Kitamura4, Si-Bum Park5, Shigenobu Kishino4, Jun Ogawa2,4, Teruo Kawada1,2, Tsuyoshi Goto1,2. 1. Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate school of Agriculture, Kyoto University, Uji, Kyoto, Japan. 2. Research Unit for Physiological Chemistry, The Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Japan. 3. Department of Food Science and Nutrition, University of Ulsan, Ulsan, South Korea. 4. Division of Applied Life Science, Graduate School of Agriculture, Kyoto University, Kyoto, Japan. 5. Laboratory of Industrial Microbiology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.
Abstract
SCOPE: 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. METHODS AND RESULTS: 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. CONCLUSION: These findings indicate that synthesized enone fatty acids show potent anti-inflammatory effects, leading to the improvement of inflammation-induced dysfunctions in adipocytes.
SCOPE: 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. METHODS AND RESULTS: 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. CONCLUSION: These findings indicate that synthesized enone fatty acids show potent anti-inflammatory effects, leading to the improvement of inflammation-induced dysfunctions in adipocytes.
Authors: Abbi R Hernandez; Jessica M Hoffman; Caesar M Hernandez; Constanza J Cortes; Patricia Jumbo-Lucioni; Mark G Baxter; Karyn A Esser; Andrew C Liu; Lori L McMahon; Jennifer L Bizon; Sara N Burke; Thomas W Buford; Christy S Carter Journal: J Gerontol A Biol Sci Med Sci Date: 2022-01-07 Impact factor: 6.591