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噻唑烷二酮通过调节硬脂酰辅酶A去饱和酶-1、脂肪酶活性、瘦素和抵抗素对肝脂肪变性产生治疗作用。

Thiazolidinedione induces a therapeutic effect on hepatosteatosis by regulating stearoyl-CoA desaturase-1, lipase activity, leptin and resistin.

作者信息

Al-Muzafar Hessah Mohammed, Amin Kamal Adel

机构信息

Department of Chemistry and Biochemistry, College of Science, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia.

出版信息

Exp Ther Med. 2018 Oct;16(4):2938-2948. doi: 10.3892/etm.2018.6563. Epub 2018 Aug 2.

Abstract

Hepatosteatosis is a disease present worldwide, which presents a number of health problems. Recently, thiazolidinedione (TZD) has been used as a therapy for lipid disorders. The present study demonstrates the potential of TZD as a treatment for hepatosteatosis and its mechanism of action, particularly focusing on its role in lipid metabolism. A total of 60 (80-90 g) rats were divided into three groups: A normal group with a standard diet, a high-fat, high-carbohydrate diet (HFCD) group or a HFCD+TZD group (n=20/group). The HFCD induced hepatosteatosis over a period of 12 weeks and the HFCD+TZD group were administered TZD in weeks 13-16. Blood and tissue samples were collected to measure hepatic function, the lipid profile, metabolism and hormone biomarkers, including serum triglyceride (TG), lipoprotein lipase (LPL), stearoyl-CoA desaturase (SCD-1), leptin and resistin. The HFCD-fed rats exhibited a significant increase in serum TG, total cholesterol, low-density lipoproteins, alanine transaminase and bilirubin compared with the normal group as well as a significant decrease in high-density lipoprotein. In addition, serum leptin and resistin were significantly elevated in the HFCD group compared with the normal group. The administration of TZD significantly increased SCD-1 activity and significantly inhibited LPL activity. It also attenuated the changes in the lipid profiles and normalized serum leptin and resistin levels. The results of the present study indicated that HFCD induced lipid abnormalities associated with hypertriglyceridemia, hypercholesterolemia and hepatosteatosis. These changes resulted from disruption to leptin and resistin, which may be due to alterations in LPL and SCD-1 activity. TZD mitigated the effects of HFCD-induced hepatosteatosis, indicating a possible regulatory effect of TZD in the development of hepatosteatosis. The authors suggest that the manipulation of SCD-1 and lipase by TZD may be useful as a treatment for hepatosteatosis.

摘要

肝脂肪变性是一种在全球范围内存在的疾病,它会引发一系列健康问题。最近,噻唑烷二酮(TZD)已被用作治疗脂质紊乱的药物。本研究证明了TZD作为治疗肝脂肪变性的潜力及其作用机制,尤其关注其在脂质代谢中的作用。总共60只(80 - 90克)大鼠被分为三组:一组为标准饮食的正常组,一组为高脂高碳水化合物饮食(HFCD)组,或一组为HFCD + TZD组(每组n = 20)。HFCD在12周内诱导肝脂肪变性,HFCD + TZD组在第13 - 16周给予TZD。采集血液和组织样本以测量肝功能、脂质谱、代谢和激素生物标志物,包括血清甘油三酯(TG)、脂蛋白脂肪酶(LPL)、硬脂酰辅酶A去饱和酶(SCD - 1)、瘦素和抵抗素。与正常组相比,喂食HFCD的大鼠血清TG、总胆固醇、低密度脂蛋白、丙氨酸转氨酶和胆红素显著升高,高密度脂蛋白显著降低。此外,与正常组相比,HFCD组血清瘦素和抵抗素显著升高。给予TZD显著增加了SCD - 1活性,并显著抑制了LPL活性。它还减轻了脂质谱的变化,并使血清瘦素和抵抗素水平恢复正常。本研究结果表明,HFCD诱导了与高甘油三酯血症、高胆固醇血症和肝脂肪变性相关的脂质异常。这些变化是由于瘦素和抵抗素的破坏导致的,这可能是由于LPL和SCD - 1活性的改变。TZD减轻了HFCD诱导的肝脂肪变性的影响,表明TZD在肝脂肪变性发展过程中可能具有调节作用。作者认为,TZD对SCD - 1和脂肪酶的调控作用可能有助于治疗肝脂肪变性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcaa/6125847/9d47d3b8355a/etm-16-04-2938-g00.jpg

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