Saikosaponin A and D Inhibit Adipogenesis via the AMPK and MAPK Signaling Pathways in 3T3-L1 Adipocytes.
Saikosaponin A and D Inhibit Adipogenesis via the AMPK and MAPK Signaling Pathways in 3T3-L1 Adipocytes.
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DOI：
10.3390/ijms222111409
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发表时间：
2021-10-22
影响因子：
5.6
通讯作者：
Choi CI
中科院分区：
文献类型：
--
作者：
Lim SH;Lee HS;Han HK;Choi CI
肥胖是由遗传、药物、营养和其他环境因素引起的脂质代谢紊乱。其特征是脂肪细胞中脂质过量积累的复杂情况。脂肪生成是一个分化过程，将前脂肪细胞转化为成熟脂肪细胞，并导致过度脂肪沉积。柴胡皂苷 A (SSA) 和柴胡皂苷 D (SSD) 是从柴胡根中分离出来的三萜皂苷，长期以来一直用于治疗炎症、发烧和肝脏疾病。然而，人们对这些成分对脂质积累和肥胖的影响知之甚少。我们研究了 SSA 和 SSD 在小鼠 3T3-L1 脂肪细胞中的抗肥胖作用。进行MTT测定来测量细胞活力，并进行油红O染色来测定脂质积累。通过蛋白质印迹测定和定量逆转录聚合酶链反应（qRT-PCR）在蛋白质和mRNA水平评估各种脂肪形成转录因子。在这里，我们发现 SSA 和 SSD 在测试浓度范围 (0.938–15 µM) 内显着抑制脂质积累，而不影响细胞活力。 SSA 和 SSD 还剂量依赖性地抑制过氧化物酶体增殖物激活受体 γ (PPARγ)、CCAAT/增强子结合蛋白 α (C/EBPα)、甾醇调节元件结合蛋白 1c (SREBP-1c) 和脂联素的表达。此外，这些转录因子的减少导致多种脂肪生成基因的表达受到抑制，包括脂肪酸结合蛋白（FABP4）、脂肪酸合酶（FAS）和脂蛋白脂肪酶（LPL）。此外，SSA和SSD增强了腺苷单磷酸激活蛋白激酶（AMPK）及其底物乙酰辅酶A羧化酶（ACC）的磷酸化，并抑制细胞外调节激酶1/2（ERK1/2）和p38的磷酸化，但不抑制c-Jun-N末端激酶（JNK）。这些结果表明，SSA 和 SSD 在脂肪细胞分化的早期阶段通过 AMPK 或丝裂原激活蛋白激酶 (MAPK) 途径抑制脂肪生成。这是第一项关于 SSA 和 SSD 的抗脂肪作用的研究，需要在动物和人类中进行进一步的研究，以确认柴胡皂苷作为肥胖治疗剂的潜力。
Obesity is a lipid metabolism disorder caused by genetic, medicinal, nutritional, and other environmental factors. It is characterized by a complex condition of excess lipid accumulation in adipocytes. Adipogenesis is a differentiation process that converts preadipocytes into mature adipocytes and contributes to excessive fat deposition. Saikosaponin A (SSA) and saikosaponin D (SSD) are triterpenoid saponins separated from the root of the Bupleurum chinensis, which has long been used to treat inflammation, fever, and liver diseases. However, the effects of these constituents on lipid accumulation and obesity are poorly understood. We investigated the anti-obesity effects of SSA and SSD in mouse 3T3-L1 adipocytes. The MTT assay was performed to measure cell viability, and Oil Red O staining was conducted to determine lipid accumulation. Various adipogenic transcription factors were evaluated at the protein and mRNA levels by Western blot assay and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Here, we showed that SSA and SSD significantly inhibited lipid accumulation without affecting cell viability within the range of the tested concentrations (0.938–15 µM). SSA and SSD also dose-dependently suppressed the expression of peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer binding protein alpha (C/EBPα), sterol regulatory element binding protein-1c (SREBP-1c), and adiponectin. Furthermore, the decrease of these transcriptional factors resulted in the repressed expression of several lipogenic genes including fatty acid binding protein (FABP4), fatty acid synthase (FAS), and lipoprotein lipase (LPL). In addition, SSA and SSD enhanced the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and its substrate, acetyl-CoA carboxylase (ACC), and inhibited the phosphorylation of extracellular-regulated kinase 1/2 (ERK1/2) and p38, but not c-Jun-N-terminal kinase (JNK). These results suggest that SSA and SSD inhibit adipogenesis through the AMPK or mitogen-activated protein kinase (MAPK) pathways in the early stages of adipocyte differentiation. This is the first study on the anti-adipogenic effects of SSA and SSD, and further research in animals and humans is necessary to confirm the potential of saikosaponins as therapeutic agents for obesity.
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影响因子：
6.5
作者：
Fu, YC;Luo, NL;Garvey, WT
通讯作者：
Garvey, WT
影响因子：
--
作者：
Qi, Renli;Liu, Hong;Huang, Jinxiu
通讯作者：
Huang, Jinxiu
DOI：
10.1042/bj20091112
发表时间：
2009-12-14
期刊：
The Biochemical journal
影响因子：
--
作者：
Payne VA;Au WS;Lowe CE;Rahman SM;Friedman JE;O'Rahilly S;Rochford JJ
通讯作者：
Rochford JJ
DOI：
10.1530/joe-16-0211
发表时间：
2016-12
期刊：
The Journal of endocrinology
影响因子：
--
作者：
Luo L;Liu M
通讯作者：
Liu M
影响因子：
8.9
作者：
Haczeyni, F.;Bell-Anderson, K. S.;Farrell, G. C.
通讯作者：
Farrell, G. C.