Alzubi Ala, Monk Jennifer M
Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada.
Biomedicines. 2024 Nov 16;12(11):2621. doi: 10.3390/biomedicines12112621.
Microbial fermentation of non-digestible carbohydrates and/or protein produces short-chain fatty acids (SCFA), whereas branched-chain fatty acids (BCFA) are produced from protein fermentation. The effects of individual SCFA and BCFA of comparable carbon chain length on adipocyte inflammation have not been investigated. : To compare the effects of SCFA and BCFA on inflammatory mediator secretion in an adipocyte cell culture model designed to recapitulate obesity-associated adipocyte inflammation under normoxic and hypoxic conditions. The 3T3-L1 adipocytes were cultured (24 h) without (Control, Con) and with 1 mmol/L of SCFA (butyric acid (But) or valeric acid (Val)) or 1 mmol/L of BCFA (isobutyric acid (IsoBut) or isovaleric acid (IsoVal)) and were unstimulated (cells alone, = 6/treatment), or stimulated with 10 ng/mL lipopolysaccharide (LPS, inflammatory stimulus, = 8/treatment) or 10 ng/mL LPS + 100 µmol/L of the hypoxia memetic cobalt chloride (LPS/CC, inflammatory/hypoxic stimulus, = 8/treatment). : Compared to Con + LPS, But + LPS reduced secreted protein levels of interleukin (IL)-1β, IL-6, macrophage chemoattractant protein (MCP)-1/chemokine ligand (CCL)2, MCP3/CCL7, macrophage inflammatory protein (MIP)-1α/CCL3 and regulated upon activation, normal T cell expressed, and secreted (RANTES)/CCL5 and decreased intracellular protein expression of the ratio of phosphorylated to total signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa B (NFκB) p65 ( < 0.05). Val + LPS reduced IL-6 secretion and increased MCP-1/CCL2 secretion compared to Con + LPS and exhibited a different inflammatory mediator secretory profile from But + LPS ( < 0.05), indicating that individual SCFA exert individual effects. There were no differences in the secretory profile of the BCFA IsoBut + LPS and IsoVal + LPS ( > 0.05). Alternatively, under inflammatory hypoxic conditions (LPS/CC) Val, IsoVal, and IsoBut all increased secretion of IL-6, MCP-1/CCL2 and MIP-1α/CCL3 compared to Con ( < 0.05), whereas mediator secretion did not differ between But and Con ( > 0.05), indicating that the proinflammatory effects of SCFA and BCFA was attenuated by But. Interestingly, But + LPS/CC decreased STAT3 activation versus Con + LPS/CC ( < 0.05). : The decreased secretion of inflammatory mediators that is attributable to But highlights the fact that individual SCFA and BCFA exert differential effects on adipocyte inflammation under normoxic and hypoxic conditions.
不可消化的碳水化合物和/或蛋白质的微生物发酵产生短链脂肪酸（SCFA），而支链脂肪酸（BCFA）则由蛋白质发酵产生。尚未研究具有可比碳链长度的单个SCFA和BCFA对脂肪细胞炎症的影响。：为了比较SCFA和BCFA对脂肪细胞培养模型中炎症介质分泌的影响，该模型旨在概括常氧和低氧条件下与肥胖相关的脂肪细胞炎症。将3T3-L1脂肪细胞在无（对照，Con）和有1 mmol/L SCFA（丁酸（But）或戊酸（Val））或1 mmol/L BCFA（异丁酸（IsoBut）或异戊酸（IsoVal））的情况下培养（24小时），并且未受到刺激（仅细胞，每组 = 6），或用10 ng/mL脂多糖（LPS，炎症刺激物，每组 = 8）或10 ng/mL LPS + 100 µmol/L低氧模拟物氯化钴（LPS/CC，炎症/低氧刺激物，每组 = 8）进行刺激。：与Con + LPS相比，But + LPS降低了白细胞介素（IL）-1β、IL-6、巨噬细胞趋化蛋白（MCP）-1/趋化因子配体（CCL）2、MCP3/CCL7、巨噬细胞炎性蛋白（MIP）-1α/CCL3以及活化调节正常T细胞表达和分泌因子（RANTES）/CCL5的分泌蛋白水平，并降低了磷酸化与总信号转导和转录激活因子3（STAT3）以及核因子κB（NFκB）p65比值的细胞内蛋白表达（P < 0.05）。与Con + LPS相比，Val + LPS降低了IL-6的分泌并增加了MCP-1/CCL2的分泌，并且表现出与But + LPS不同的炎症介质分泌谱（P < 0.05），表明单个SCFA发挥各自的作用。BCFA IsoBut + LPS和IsoVal + LPS的分泌谱没有差异（P > 0.05）。另外，在炎症性低氧条件下（LPS/CC），与Con相比，Val、IsoVal和IsoBut均增加了IL-6、MCP-1/CCL2和MIP-1α/CCL3的分泌（P < 0.05），而But和Con之间的介质分泌没有差异（P > 0.05），表明But减弱了SCFA和BCFA的促炎作用。有趣的是，与Con + LPS/CC相比，But + LPS/CC降低了STAT3的活化（P < 0.05）。：But导致的炎症介质分泌减少突出了以下事实，即单个SCFA和BCFA在常氧和低氧条件下对脂肪细胞炎症发挥不同的作用。
