Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil 05508-900.
J Nutr Biochem. 2011 Sep;22(9):849-55. doi: 10.1016/j.jnutbio.2010.07.009. Epub 2010 Dec 16.
Short chain fatty acids (SCFAs) are fermentation products of anaerobic bacteria. More than just being an important energy source for intestinal epithelial cells, these compounds are modulators of leukocyte function and potential targets for the development of new drugs. The aim of this study was to evaluate the effects of SCFAs (acetate, propionate and butyrate) on production of nitric oxide (NO) and proinflammatory cytokines [tumor necrosis factor α (TNF-α) and cytokine-induced neutrophil chemoattractant-2 (CINC-2αβ)] by rat neutrophils. The involvement of nuclear factor κB (NF-κB) and histone deacetylase (HDAC) was examined. The effect of butyrate was also investigated in vivo after oral administration of tributyrin (a pro-drug of butyrate). Propionate and butyrate diminished TNF-α, CINC-2αβ and NO production by LPS-stimulated neutrophils. We also observed that these fatty acids inhibit HDAC activity and NF-κB activation, which might be involved in the attenuation of the LPS response. Products of cyclooxygenase and 5-lipoxygenase are not involved in the effects of SCFAs as indicated by the results obtained with the inhibitors of these enzymes. The recruitment of neutrophils to the peritonium after intraperitoneal administration of a glycogen solution (1%) and the ex vivo production of cytokines and NO by neutrophils were attenuated in rats that previously received tributyrin. These results argue that this triglyceride may be effective in the treatment of inflammatory conditions.
短链脂肪酸（SCFAs）是厌氧菌发酵的产物。这些化合物不仅是肠道上皮细胞的重要能量来源，还是白细胞功能的调节剂，也是开发新药的潜在靶点。本研究旨在评估 SCFAs（乙酸盐、丙酸盐和丁酸盐）对大鼠中性粒细胞产生一氧化氮（NO）和促炎细胞因子[肿瘤坏死因子-α（TNF-α）和细胞因子诱导的中性粒细胞趋化因子-2（CINC-2αβ）]的影响。还研究了核因子 κB（NF-κB）和组蛋白去乙酰化酶（HDAC）的参与。还研究了丁酸盐在口服三丁酸甘油酯（丁酸盐的前体药物）后在体内的作用。丙酸盐和丁酸盐可减少 LPS 刺激的中性粒细胞产生 TNF-α、CINC-2αβ 和 NO。我们还观察到，这些脂肪酸抑制 HDAC 活性和 NF-κB 激活，这可能参与了 LPS 反应的衰减。如这些酶的抑制剂的结果所示，环加氧酶和 5-脂加氧酶的产物不参与 SCFAs 的作用。在先前接受三丁酸甘油酯治疗的大鼠中，腹腔内给予糖原溶液（1%）后中性粒细胞向腹膜募集以及中性粒细胞体外产生细胞因子和 NO 的作用减弱。这些结果表明，这种甘油三酯可能对炎症性疾病的治疗有效。
