Chen Xiaocong, Sebastian Becky M, Tang Hui, McMullen Megan M, Axhemi Armend, Jacobsen Donald W, Nagy Laura E
Department of Nutrition, Case Western Reserve University, Cleveland, OH, USA.
Hepatology. 2009 May;49(5):1554-62. doi: 10.1002/hep.22811.
Chronic ethanol feeding decreases expression of adiponectin by adipocytes and circulating adiponectin. Adiponectin treatment during chronic ethanol feeding prevents liver injury in mice. Chronic ethanol feeding also increases oxidative and endoplasmic reticulum (ER) stress in adipose tissue. Here we tested the hypothesis that supplemental taurine, an amino acid that functions as a chemical chaperone/osmolyte and enhances cellular antioxidant activity, would prevent ethanol-induced decreases in adiponectin expression and attenuate liver injury. Serum adiponectin concentrations decreased as early as 4 to 7 days after feeding rats a 36% ethanol diet. This rapid decrease was associated with increased oxidative, but not ER, stress in subcutaneous adipose tissue. Taurine prevented ethanol-induced oxidative stress and increased inflammatory cytokine expression in adipose tissue. Ethanol feeding also rapidly decreased expression of transcription factors regulating adiponectin expression (CCAAT/enhancer binding protein alpha; peroxisome proliferator-activated receptor alpha/gamma) in subcutaneous adipose tissue. Taurine prevented the ethanol-induced decrease in CCAAT/enhancer binding protein alpha and peroxisome proliferator-activated receptor alpha, normalizing adiponectin messenger (m)RNA and serum adiponectin concentrations. In the liver, taurine prevented ethanol-induced oxidative stress and attenuated tumor necrosis factor alpha expression and steatosis, at least in part, by increasing expression of genes involved in fatty acid oxidation.
In subcutaneous adipose tissue, taurine decreased ethanol-induced oxidative stress and cytokine expression, as well as normalized expression of adiponectin mRNA. Taurine prevented ethanol-induced decreases in serum adiponectin; normalized adiponectin was associated with a reduction in hepatic oxidative stress, tumor necrosis factor alpha expression, and steatosis. Taken together, these data demonstrate that taurine has important protective effects against ethanol-induced tissue injury in both adipose and liver tissue.
长期喂食乙醇会降低脂肪细胞中脂联素的表达以及循环脂联素水平。在长期喂食乙醇期间进行脂联素治疗可预防小鼠肝脏损伤。长期喂食乙醇还会增加脂肪组织中的氧化应激和内质网(ER)应激。在此,我们检验了以下假设:补充牛磺酸(一种作为化学伴侣/渗透溶质发挥作用并增强细胞抗氧化活性的氨基酸)可预防乙醇诱导的脂联素表达降低并减轻肝脏损伤。给大鼠喂食36%乙醇饮食后,血清脂联素浓度早在4至7天就开始下降。这种快速下降与皮下脂肪组织中氧化应激增加有关,但与内质网应激无关。牛磺酸可预防乙醇诱导的氧化应激,并增加脂肪组织中炎性细胞因子的表达。喂食乙醇还会迅速降低皮下脂肪组织中调节脂联素表达的转录因子(CCAAT/增强子结合蛋白α;过氧化物酶体增殖物激活受体α/γ)的表达。牛磺酸可预防乙醇诱导的CCAAT/增强子结合蛋白α和过氧化物酶体增殖物激活受体α的降低,使脂联素信使核糖核酸(mRNA)和血清脂联素浓度恢复正常。在肝脏中,牛磺酸可预防乙醇诱导的氧化应激,并至少部分通过增加参与脂肪酸氧化的基因表达来减轻肿瘤坏死因子α的表达和脂肪变性。
在皮下脂肪组织中,牛磺酸可降低乙醇诱导的氧化应激和细胞因子表达,并使脂联素mRNA表达恢复正常。牛磺酸可预防乙醇诱导的血清脂联素降低;脂联素恢复正常与肝脏氧化应激、肿瘤坏死因子α表达和脂肪变性的减轻有关。综上所述,这些数据表明牛磺酸对乙醇诱导的脂肪组织和肝脏组织损伤具有重要的保护作用。