Research Administration Team, Seoul National University Bundang Hospital, 166 Gumi-ro, Bundang-gu, Seongnam, 463-707, Korea.
Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 166 Gumi-ro, Bundang-gu, Seongnam, 463-707, Korea.
J Biomed Sci. 2018 Mar 28;25(1):27. doi: 10.1186/s12929-018-0431-7.
β-aminoisobutyric acid (BAIBA) is produced in skeletal muscle during exercise and has beneficial effects on obesity-related metabolic disorders such as diabetes and non-alcoholic fatty liver disease. Thus, it is supposed to prevent high fat diet (HFD)-induced inflammation and insulin resistance in adipose tissue though anti-inflammatory effects in obesity. Previous reports have also demonstrated strong anti-inflammatory effects of BAIBA.
We used BAIBA treated fully differentiated 3T3T-L1 mouse adipocytes to investigate the effects of exogenous BAIBA on inflammation and insulin signaling in adipocytes. Insulin signaling-mediated proteins and inflammation markers were measured by Western blot analysis. Secretion of pro-inflammatory cytokines were measured by ELISA. Lipid accumulation in differentiated 3 T3-L1 cells was stained by Oil red-O. Statistical analysis was performed by ANOVA and student's t test.
BAIBA treatment suppressed adipogenesis assessed by adipogenic markers as well as lipid accumulation after full differentiation. We showed that BAIBA treatment stimulated AMP-activated protein kinase (AMPK) phosphorylation in a dose-dependent manner and lipopolysaccharide (LPS)-induced secretion of pro-inflammatory cytokines such as TNFα and MCP-1 was abrogated in BAIBA-treated 3 T3-L1 cells. Treatment of 3 T3-L1 cells with BAIBA reduced LPS-induced NFκB and IκB phosphorylation. Furthermore, BAIBA treatment ameliorated LPS-induced impairment of insulin signaling measured by IRS-1 and Akt phosphorylation and fatty acid oxidation. Suppression of AMPK by small interfering (si) RNA significantly restored these changes.
We demonstrated anti-inflammatory and anti-insulin resistance effects of BAIBA in differentiated 3 T3-L1 cells treated with LPS through AMPK-dependent signaling. These results provide evidence for the beneficial effects of BAIBA not only in liver and skeletal muscle cells but also in adipose tissue.
β-氨基异丁酸（BAIBA）在运动过程中产生于骨骼肌中，对肥胖相关的代谢紊乱如糖尿病和非酒精性脂肪肝有有益作用。因此，它应该通过在肥胖中的抗炎作用来预防高脂肪饮食（HFD）引起的脂肪组织炎症和胰岛素抵抗。先前的报告也表明 BAIBA 具有很强的抗炎作用。
我们使用经过完全分化的 3T3T-L1 小鼠脂肪细胞处理的 BAIBA 来研究外源性 BAIBA 对脂肪细胞炎症和胰岛素信号的影响。通过 Western blot 分析测量胰岛素信号介导的蛋白和炎症标志物。通过 ELISA 测量促炎细胞因子的分泌。用油红-O 染色测定分化的 3T3-L1 细胞中的脂质积累。通过 ANOVA 和学生 t 检验进行统计分析。
BAIBA 处理抑制了脂肪生成标志物评估的脂肪生成以及完全分化后的脂质积累。我们表明，BAIBA 处理以剂量依赖性方式刺激 AMP 激活的蛋白激酶（AMPK）磷酸化，并且 BAIBA 处理消除了 LPS 诱导的促炎细胞因子如 TNFα和 MCP-1 的分泌。3T3-L1 细胞用 BAIBA 处理可降低 LPS 诱导的 NFκB 和 IκB 磷酸化。此外，BAIBA 处理改善了 LPS 诱导的胰岛素信号受损，如 IRS-1 和 Akt 磷酸化和脂肪酸氧化。用小干扰（si）RNA 抑制 AMPK 可显著恢复这些变化。
我们通过 AMPK 依赖性信号在 LPS 处理的分化的 3T3-L1 细胞中证明了 BAIBA 的抗炎和抗胰岛素抵抗作用。这些结果为 BAIBA 的有益作用提供了证据，不仅在肝脏和骨骼肌细胞中，而且在脂肪组织中也是如此。
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