Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford.
Oxford NIHR Biomedical Research Centre, Churchill Hospital, Oxford, UK.
Curr Opin Clin Nutr Metab Care. 2022 Jul 1;25(4):241-247. doi: 10.1097/MCO.0000000000000838.
Intrahepatic triglyceride (IHTG) content is determined by substrate flux to, fatty acid synthesis and partitioning within, and triglyceride disposal from the liver. Dysregulation of these processes may cause IHTG accumulation, potentially leading to nonalcoholic fatty liver disease. The aetiology of IHTG accumulation has not been fully elucidated; however, environmental factors and heritability are important. Here, we review recent evidence regarding the contribution of metabolic and genetic components of IHTG accumulation.
Obesity and insulin resistance are the primary metabolic drivers for IHTG accumulation. These risk factors have pronounced and seemingly overlapping effects on all processes involved in determining IHTG content. The strong and interchangeable associations between obesity, insulin resistance and IHTG make it challenging to determine their relative contributions. Genome-wide association studies have identified a growing list of single nucleotide polymorphisms associated with IHTG content and recent work has begun to elucidate their mechanistic effects. The mechanisms underlying metabolic and genetic drivers of IHTG appear to be distinct.
Both metabolic and genetic factors influence IHTG content by apparently distinct mechanisms. Further work is needed to determine metabolic and genetic interaction effects, which may lead to more personalized and potentially efficacious therapeutic interventions. The development of a comprehensive polygenic risk score for IHTG content may help facilitate this.
肝内甘油三酯（IHTG）含量由进入肝脏的底物流量、脂肪酸合成和分配以及从肝脏清除甘油三酯决定。这些过程的失调可能导致 IHTG 积累，从而可能导致非酒精性脂肪性肝病。IHTG 积累的病因尚未完全阐明；然而，环境因素和遗传性是重要的。在这里，我们回顾了最近关于 IHTG 积累的代谢和遗传成分的贡献的证据。
肥胖和胰岛素抵抗是非酒精性脂肪肝的主要代谢驱动因素，这些危险因素对决定 IHTG 含量的所有过程都有明显且似乎重叠的影响。肥胖、胰岛素抵抗和 IHTG 之间的强烈和可互换的关联使得确定它们的相对贡献变得具有挑战性。全基因组关联研究已经确定了越来越多与 IHTG 含量相关的单核苷酸多态性，最近的工作已经开始阐明它们的机制作用。代谢和遗传驱动因素影响 IHTG 的机制似乎是不同的。
代谢和遗传因素通过明显不同的机制影响 IHTG 含量。需要进一步的工作来确定代谢和遗传的相互作用效应，这可能会导致更个性化和潜在有效的治疗干预措施。IHTG 含量的综合多基因风险评分的发展可能有助于实现这一目标。
