Lo Chia-Wen, Lee Jyun-Lin, Tsai Wei-Ting, Huang Chin-Shiu, Yang Ya-Chen, Lii Chong-Kuei, Chen Haw-Wen
Department of Nutrition, China Medical University, Taichung, Taiwan; Department of Nutrition, College of Medical and Health Care, Hung-Kuang University, Taichung, Taiwan.
School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan.
J Nutr Biochem. 2025 Oct;144:109981. doi: 10.1016/j.jnutbio.2025.109981. Epub 2025 May 29.
The global prevalence of overweight and obesity has risen sharply over the past few decades as a result of excess calorie intake and sedentary lifestyles. Obesity increases the risk for various metabolic disorders, such as hyperlipidemia, fatty liver disease, and diabetes mellitus. Isothiocyanates, which are abundant in cruciferous vegetables, have been shown to exhibit anticancer, anti-inflammatory, and antioxidant properties. However, the efficacy of benzyl isothiocyanate (BITC) in preventing the adverse effects of obesity, such as hepatic steatosis and insulin resistance, remains uncertain. To address this knowledge gap, we assessed whether BITC protects against hepatic insulin resistance by using primary mouse hepatocytes and AML12 cells treated with palmitic acid (PA) and mice fed a high-fat diet supplemented with cholesterol and cholic acid (HFCCD). We found that the impairments in insulin sensitivity caused by PA, such as decreases in the phosphorylation of insulin receptor substrate (IRS) 1 (Tyr608), Akt, glycogen synthase kinase (GSK) 3β, and FOXO1 and increases in the expression of glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase 1 (PEPCK) mRNA in hepatocytes, were mitigated by pretreatment with BITC. BITC also attenuated PA-induced hepatic lipid accumulation and reactive oxygen species production. In vivo, BITC significantly reduced blood glucose levels and the HOMA-IR and inhibited hepatic lipid accumulation, IRS1 phosphorylation at Ser307, and G6Pase and PEPCK expression compared with that in mice fed the HFCCD alone. These results show that BITC ameliorates the lipotoxicity associated with insulin resistance by activating the IR/IRS/Akt/FOXO1 and GSK3β pathways, which leads to decreased gluconeogenesis and increased glycogen synthesis.
在过去几十年中，由于热量摄入过多和久坐不动的生活方式，全球超重和肥胖的患病率急剧上升。肥胖会增加各种代谢紊乱的风险，如高脂血症、脂肪肝疾病和糖尿病。异硫氰酸盐在十字花科蔬菜中含量丰富，已被证明具有抗癌、抗炎和抗氧化特性。然而，苄基异硫氰酸盐（BITC）在预防肥胖的不良影响（如肝脂肪变性和胰岛素抵抗）方面的功效仍不确定。为了填补这一知识空白，我们使用棕榈酸（PA）处理的原代小鼠肝细胞和AML12细胞以及喂食补充胆固醇和胆酸的高脂饮食（HFCCD）的小鼠，评估了BITC是否能预防肝胰岛素抵抗。我们发现，PA引起的胰岛素敏感性损害，如肝细胞中胰岛素受体底物（IRS）1（Tyr608）、Akt、糖原合酶激酶（GSK）3β和FOXO1磷酸化水平降低，以及葡萄糖-6-磷酸酶（G6Pase）和磷酸烯醇丙酮酸羧激酶1（PEPCK）mRNA表达增加，通过BITC预处理得到缓解。BITC还减轻了PA诱导的肝脏脂质积累和活性氧生成。在体内，与仅喂食HFCCD的小鼠相比，BITC显著降低了血糖水平和HOMA-IR，并抑制了肝脏脂质积累、Ser307处的IRS1磷酸化以及G6Pase和PEPCK的表达。这些结果表明，BITC通过激活IR/IRS/Akt/FOXO1和GSK3β途径改善了与胰岛素抵抗相关的脂毒性，从而导致糖异生减少和糖原合成增加。
