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The role of hepatic lipid composition in obesity-related metabolic disease
Liver International ( IF 6.7 ) Pub Date : 2021-09-21 , DOI: 10.1111/liv.15059 Scott A Willis 1, 2 , Stephen J Bawden 3, 4 , Sundus Malaikah 1, 2, 5 , Jack A Sargeant 2, 6 , David J Stensel 1, 2 , Guruprasad P Aithal 4, 7 , James A King 1, 2
Liver International ( IF 6.7 ) Pub Date : 2021-09-21 , DOI: 10.1111/liv.15059 Scott A Willis 1, 2 , Stephen J Bawden 3, 4 , Sundus Malaikah 1, 2, 5 , Jack A Sargeant 2, 6 , David J Stensel 1, 2 , Guruprasad P Aithal 4, 7 , James A King 1, 2
Affiliation
Obesity is a primary antecedent to non-alcoholic fatty liver disease whose cardinal feature is excessive hepatic lipid accumulation. Although total hepatic lipid content closely associates with hepatic and systemic metabolic dysfunction, accumulating evidence suggests that the composition of hepatic lipids may be more discriminatory. This review summarises cross-sectional human studies using liver biopsy/lipidomics and proton magnetic resonance spectroscopy to characterise hepatic lipid composition in people with obesity and related metabolic disease. A comprehensive literature search identified 26 relevant studies published up to 31st March 2021 which were included in the review. The available evidence provides a consistent picture showing that people with hepatic steatosis possess elevated saturated and/or monounsaturated hepatic lipids and a reduced proportion of polyunsaturated hepatic lipids. This altered hepatic lipid profile associates more directly with metabolic derangements, such as insulin resistance, and may be exacerbated in non-alcoholic steatohepatitis. Further evidence from lipidomic studies suggests that these deleterious changes may be related to defects in lipid desaturation and elongation, and an augmentation of the de novo lipogenic pathway. These observations are consistent with mechanistic studies implicating saturated fatty acids and associated bioactive lipid intermediates (ceramides, lysophosphatidylcholines and diacylglycerol) in the development of hepatic lipotoxicity and wider metabolic dysfunction, whilst monounsaturated fatty acids and polyunsaturated fatty acids may exhibit a protective role. Future studies are needed to prospectively determine the relevance of hepatic lipid composition for hepatic and non-hepatic morbidity and mortality; and to further evaluate the impact of therapeutic interventions such as pharmacotherapy and lifestyle interventions.
中文翻译:
肝脏脂质成分在肥胖相关代谢疾病中的作用
肥胖是非酒精性脂肪性肝病的主要前因,其主要特征是肝脏脂质积累过多。尽管肝脏总脂质含量与肝脏和全身代谢功能障碍密切相关,但越来越多的证据表明肝脏脂质的组成可能更具歧视性。本综述总结了使用肝活检/脂质组学和质子磁共振波谱来表征肥胖和相关代谢疾病患者肝脏脂质成分的横断面人体研究。一项全面的文献检索确定了截至 2021 年 3 月 31 日发表的 26 项相关研究,这些研究被纳入审查。现有证据提供了一致的图片,表明患有肝脂肪变性的人具有升高的饱和和/或单不饱和肝脂质以及减少的多不饱和肝脂质比例。这种改变的肝脏脂质谱与代谢紊乱(例如胰岛素抵抗)更直接相关,并且可能在非酒精性脂肪性肝炎中加剧。来自脂质组学研究的进一步证据表明,这些有害变化可能与脂质去饱和和伸长缺陷以及从头脂肪生成途径的增加有关。这些观察结果与涉及饱和脂肪酸和相关的生物活性脂质中间体(神经酰胺、溶血磷脂酰胆碱和二酰基甘油)在肝脂毒性和更广泛的代谢功能障碍的发展中,而单不饱和脂肪酸和多不饱和脂肪酸可能表现出保护作用。未来的研究需要前瞻性地确定肝脏脂质成分与肝脏和非肝脏发病率和死亡率的相关性;并进一步评估药物治疗和生活方式干预等治疗干预措施的影响。
更新日期:2021-09-21
中文翻译:
肝脏脂质成分在肥胖相关代谢疾病中的作用
肥胖是非酒精性脂肪性肝病的主要前因,其主要特征是肝脏脂质积累过多。尽管肝脏总脂质含量与肝脏和全身代谢功能障碍密切相关,但越来越多的证据表明肝脏脂质的组成可能更具歧视性。本综述总结了使用肝活检/脂质组学和质子磁共振波谱来表征肥胖和相关代谢疾病患者肝脏脂质成分的横断面人体研究。一项全面的文献检索确定了截至 2021 年 3 月 31 日发表的 26 项相关研究,这些研究被纳入审查。现有证据提供了一致的图片,表明患有肝脂肪变性的人具有升高的饱和和/或单不饱和肝脂质以及减少的多不饱和肝脂质比例。这种改变的肝脏脂质谱与代谢紊乱(例如胰岛素抵抗)更直接相关,并且可能在非酒精性脂肪性肝炎中加剧。来自脂质组学研究的进一步证据表明,这些有害变化可能与脂质去饱和和伸长缺陷以及从头脂肪生成途径的增加有关。这些观察结果与涉及饱和脂肪酸和相关的生物活性脂质中间体(神经酰胺、溶血磷脂酰胆碱和二酰基甘油)在肝脂毒性和更广泛的代谢功能障碍的发展中,而单不饱和脂肪酸和多不饱和脂肪酸可能表现出保护作用。未来的研究需要前瞻性地确定肝脏脂质成分与肝脏和非肝脏发病率和死亡率的相关性;并进一步评估药物治疗和生活方式干预等治疗干预措施的影响。