Alzubi Ala, Glowacki Hannah X, Burns Jessie L, Van Kelsey, Martin Jamie L A, Monk Jennifer M
Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada.
Nutrients. 2025 Feb 4;17(3):571. doi: 10.3390/nu17030571.
Short-chain fatty acids (SCFAs) produced from microbial fermentation of non-digestible carbohydrates and protein have been shown to modulate adipocyte adipokine secretion and metabolic function, which has implications for mitigating dysfunction in obese adipose tissue; however, the individual effects of different SCFAs and the optimal concentration required is unknown. The purpose of this study was to dose-dependently determine the effects of individual SCFAs on adipocyte adipokine secretion and metabolic function.
We recapitulated the obese adipocyte inflammatory conditions using mature 3T3-L1 adipocytes and a physiological concentration of lipopolysaccharide (LPS) ± individual SCFAs, namely acetate, propionate, and butyrate, in a dose-dependent manner (0.25 mM, 0.5 mM, and 1 mM) for 24 h.
SCFAs dose-dependently affected inflammatory adipokine secretion, wherein at 1 mM, all three SCFAs reduced the secretion of leptin, IL-6 and IL-1β, but only propionate and butyrate reduced MCP-1/CCL2 and MIP-1α/CCL3 compared to control ( < 0.05). Interestingly, 1 mM acetate increased RANTES/CCL5 secretion versus control, whereas propionate and butyrate decreased RANTES/CCL5 secretion, and only 1 mM propionate reduced MCP-3/CCL7 secretion ( < 0.05). At the lower 0.5 mM concentration, both propionate and butyrate reduced IL-6 and IL-1β secretion compared to control ( < 0.05), and there was no difference in adipokine secretion between groups at the 0.25 mM SCFA concentration ( > 0.05). Intracellular protein expression in the ratio of phosphorylated-to-total STAT3 was reduced by all SCFAs at 1 mM and by propionate and butyrate at 0.5 mM versus control ( < 0.05). The ratio fo phosphorylated-to-total NFκB p65 expression was reduced by propionate and butyrate at 1 mM and by butyrate alone at 0.5 mM compared to control ( < 0.05). Basal (no insulin stimulation) and insulin-stimulated glucose uptake did not differ between control and any 1 mM SCFA treatment conditions ( > 0.05).
Individual SCFAs exert different dose-dependent effects on LPS-stimulated adipocyte function.
由不可消化的碳水化合物和蛋白质经微生物发酵产生的短链脂肪酸（SCFAs）已被证明可调节脂肪细胞脂肪因子的分泌和代谢功能，这对减轻肥胖脂肪组织的功能障碍具有重要意义；然而，不同SCFAs的个体效应以及所需的最佳浓度尚不清楚。本研究的目的是剂量依赖性地确定个体SCFAs对脂肪细胞脂肪因子分泌和代谢功能的影响。
我们使用成熟的3T3-L1脂肪细胞和生理浓度的脂多糖（LPS）±个体SCFAs（即乙酸盐、丙酸盐和丁酸盐），以剂量依赖性方式（0.25 mM、0.5 mM和1 mM）模拟肥胖脂肪细胞炎症状态，处理24小时。
SCFAs以剂量依赖性方式影响炎症脂肪因子的分泌，其中在1 mM时，所有三种SCFAs均降低了瘦素、IL-6和IL-1β的分泌，但与对照组相比，只有丙酸盐和丁酸盐降低了MCP-1/CCL2和MIP-1α/CCL3的分泌（P<0.05）。有趣的是，与对照组相比，1 mM乙酸盐增加了RANTES/CCL5的分泌，而丙酸盐和丁酸盐降低了RANTES/CCL5的分泌，只有1 mM丙酸盐降低了MCP-3/CCL7的分泌（P<0.05）。在较低的0.5 mM浓度下，与对照组相比，丙酸盐和丁酸盐均降低了IL-6和IL-1β的分泌（P<0.05），在0.25 mM SCFA浓度下，各组间脂肪因子分泌无差异（P>0.05）。与对照组相比，所有SCFAs在1 mM时以及丙酸盐和丁酸盐在0.5 mM时均可降低磷酸化STAT3与总STAT3的细胞内蛋白表达比值（P<0.05）。与对照组相比，丙酸盐和丁酸盐在1 mM时以及仅丁酸盐在0.5 mM时可降低磷酸化NFκB p65与总NFκB p65的表达比值（P<0.05）。在基础状态（无胰岛素刺激）和胰岛素刺激下，对照组与任何1 mM SCFA处理条件下的葡萄糖摄取均无差异（P>0.05）。
个体SCFAs对LPS刺激的脂肪细胞功能具有不同的剂量依赖性影响。
