Department of Medical Biotechnology, Dongguk University, Seoul 04620, Republic of Korea.
College of Korean Medicine, Dongguk University, Goyang 10326, Republic of Korea.
Life Sci. 2021 Oct 1;282:119668. doi: 10.1016/j.lfs.2021.119668. Epub 2021 Jun 1.
Berteroin (5-methylthiopentyl isothiocyanate) is a naturally occurring sulforaphane analog containing a non-oxidized sulfur atom in cruciferous vegetables. The objectives of the present study were to determine the effects of berteroin on lipid metabolism in hepatocytes and adipocytes and to elucidate the mechanisms involved.
The effect of berteroin on lipid metabolism were evaluated in liver X receptor α agonist-stimulated HepG2 cells and adipocyte differentiation-induced 3T3-L1 cells using MTT assay, western blot, real time polymerase chain reaction, oil red O staining, and triglyceride assay.
T0901317 treatment increased the expression of sterol regulatory element binding protein (SREBP)-1c, a major transcription factor that mediates lipogenesis, and berteroin pretreatment significantly inhibited the expressions of T0901317-induced SREBP-1c and lipogenic genes. Especially, berteroin had a greater inhibitory effect on T0901317-induced SREBP-1c activation than sulforaphane, AICAR, or metformin. Berteroin also markedly suppressed lipid droplet formations and triglyceride accumulations caused by both T0901317 stimulation in HepG2 hepatocytes and differentiation induction in 3T3-L1 preadipocytes. However, berteroin significantly increased the expression of mitochondrial fatty acid oxidation-related genes (carnitine palmitoyltransferase 1 (CPT-1) and peroxisome proliferator-activated receptor gamma coactivator-1α) and the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) in HepG2 cells. Interestingly, effects of berteroin on the expressions of SREBP-1c protein and CPT-1 mRNA were remarkably prevented by compound C (an AMPK inhibitor).
Our results suggest berteroin-inhibited hepatic lipid accumulation and adipocyte differentiation might be mediated by AMPK activation and that berteroin might be useful for the prevention, amelioration, and treatment of metabolic diseases, including hepatic steatosis.
Berteroin（5-甲基巯基戊基异硫氰酸酯）是十字花科蔬菜中天然存在的一种硫代葡萄糖苷类似物，含有一个非氧化的硫原子。本研究的目的是确定 berteroin 对肝细胞和脂肪细胞脂质代谢的影响，并阐明其相关机制。
采用 MTT 法、western blot、实时聚合酶链反应、油红 O 染色和三酰甘油测定法，在肝 X 受体 α 激动剂刺激的 HepG2 细胞和诱导脂肪细胞分化的 3T3-L1 细胞中评价 berteroin 对脂质代谢的影响。
T0901317 处理增加了固醇调节元件结合蛋白 1c（SREBP-1c）的表达，SREBP-1c 是介导脂肪生成的主要转录因子，berteroin 预处理显著抑制了 T0901317 诱导的 SREBP-1c 和脂肪生成基因的表达。特别是，berteroin 对 T0901317 诱导的 SREBP-1c 激活的抑制作用大于萝卜硫素、AICAR 或二甲双胍。Berteroin 还显著抑制了 T0901317 刺激 HepG2 肝细胞和 3T3-L1 前脂肪细胞分化诱导的脂质滴形成和三酰甘油积累。然而，berteroin 显著增加了线粒体脂肪酸氧化相关基因（肉碱棕榈酰转移酶 1（CPT-1）和过氧化物酶体增殖物激活受体 γ 共激活因子 1α）的表达和 HepG2 细胞中腺苷单磷酸激活蛋白激酶（AMPK）的磷酸化。有趣的是，Berteroin 对 SREBP-1c 蛋白表达和 CPT-1mRNA 的作用被化合物 C（AMPK 抑制剂）显著阻止。
我们的结果表明，berteroin 抑制肝脂质积累和脂肪细胞分化可能是通过 AMPK 激活介导的，berteroin 可能对预防、改善和治疗代谢性疾病，包括肝脂肪变性，具有重要意义。
