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硬脂酰辅酶 A 去饱和酶 1 活性升高与酒精相关性肝病有关。

Elevated stearoyl-CoA desaturase 1 activity is associated with alcohol-associated liver disease.

机构信息

Office of the Clinical Director, National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institutes of Health (NIH), Bethesda, MD, United States.

Human Psychopharmacology Laboratory, NIAAA, NIH, Bethesda, MD, United States; Addictions Division, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Division of Neurosciences and Clinical Translation, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Department of Pharmacology & Toxicology, University of Toronto, Toronto, Ontario, Canada; Department of Psychological Clinical Science, University of Toronto, Toronto, Ontario, Canada.

出版信息

Alcohol. 2022 Aug;102:51-57. doi: 10.1016/j.alcohol.2022.04.001. Epub 2022 Apr 19.

Abstract

Chronic binge drinking induces hepatic lipid accumulation, but only certain individuals develop alcohol-associated liver disease (ALD). Specific patterns of lipid accumulation are thought to be associated with ALD, but this has not been comprehensively investigated to date. We analyzed plasma fatty acid levels, quantified by gas chromatography-mass spectrometry, in a sample of patients with alcohol use disorder (AUD). Given that elevation in serum alanine transaminase (ALT) levels are strongly associated with ALD, patients were stratified into two groups based on ALT levels: an ALD group (ALT >40 IU/L) and a non-ALD group (ALT ≤40 IU/L). There was a shift toward greater concentrations of monounsaturated fatty acids in the ALD group compared to the non-ALD group. Stearoyl-CoA desaturase (SCD1) activity in the ALD group was then estimated as the ratio of palmitoleic acid (16:1) to palmitic acid (16:0). SCD1 activity was greater in the ALD than the non-ALD group. A series of linear regression models demonstrated that SCD1 activity mediated the association between binge drinking and ALD. These findings provide initial evidence that SCD1 activity may be associated with ALD. If validated prospectively, elevated SCD1 activity could potentially be used as a biomarker to identify individuals at high risk for developing ALD.

摘要

慢性 binge 饮酒会导致肝脏脂质积累,但只有某些人会发展为酒精相关肝病 (ALD)。据认为,特定的脂质积累模式与 ALD 有关,但迄今为止尚未对此进行全面研究。我们分析了酒精使用障碍 (AUD) 患者样本中的血浆脂肪酸水平,这些水平通过气相色谱-质谱法进行定量。鉴于血清丙氨酸转氨酶 (ALT) 水平升高与 ALD 强烈相关,因此根据 ALT 水平将患者分为两组:ALD 组 (ALT >40 IU/L) 和非 ALD 组 (ALT ≤40 IU/L)。与非 ALD 组相比,ALD 组的单不饱和脂肪酸浓度更高。然后,通过将棕榈油酸 (16:1) 与棕榈酸 (16:0) 的比值来估计 ALD 组中的硬脂酰辅酶 A 去饱和酶 (SCD1) 活性。ALD 组中的 SCD1 活性大于非 ALD 组。一系列线性回归模型表明,SCD1 活性介导了 binge 饮酒与 ALD 之间的关联。这些发现提供了初步证据,表明 SCD1 活性可能与 ALD 有关。如果前瞻性验证,升高的 SCD1 活性可能被用作生物标志物来识别发生 ALD 风险高的个体。

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SCD1 deficiency protects mice against ethanol-induced liver injury.硬脂酰辅酶A去饱和酶1缺乏可保护小鼠免受乙醇诱导的肝损伤。
Biochim Biophys Acta. 2016 Nov;1861(11):1662-1670. doi: 10.1016/j.bbalip.2016.07.012. Epub 2016 Jul 28.

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