Srnic Nikola, Westcott Felix, Caney Eleanor, Hodson Leanne
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford OX3 7LE, UK.
Oxford NIHR Biomedical Research Centre, Churchill Hospital, Oxford OX3 7LE, UK.
Dis Model Mech. 2025 Jan 1;18(1). doi: 10.1242/dmm.050878. Epub 2025 Jan 29.
The excessive accumulation of intrahepatic triglyceride (IHTG) in the liver is a risk factor for metabolic diseases, including type 2 diabetes and cardiovascular disease. IHTG can excessively accumulate owing to imbalances in the delivery, synthesis, storage and disposal of fat to, in and from the liver. Although obesity is strongly associated with IHTG accumulation, emerging evidence suggests that the composition of dietary fat, in addition to its quantity, plays a role in mediating IHTG accumulation. Evidence from human cross-sectional and interventional studies indicates that diets enriched with saturated fat compared to other fat types and carbohydrates produce divergent effects on IHTG content. However, the mechanistic reasons for these observations remain unknown. Given the challenges of investigating such mechanisms in humans, cellular models are needed that can recapitulate human hepatocyte fatty acid metabolism. Here, we review what is known from human studies about how dietary fat, its quantity and composition contribute to IHTG accumulation. We also explore the effects of fatty acid composition on hepatocellular fat metabolism from data generated in cellular models to help explain the divergences observed in in vivo studies.
肝脏内肝内甘油三酯（IHTG）的过度积累是包括2型糖尿病和心血管疾病在内的代谢性疾病的一个危险因素。由于肝脏脂肪的输送、合成、储存和处置失衡，IHTG会过度积累。尽管肥胖与IHTG积累密切相关，但新出现的证据表明，膳食脂肪的组成除了其数量外，在介导IHTG积累中也起作用。来自人类横断面和干预性研究的证据表明，与其他脂肪类型和碳水化合物相比，富含饱和脂肪的饮食对IHTG含量产生不同的影响。然而，这些观察结果的机制原因仍然未知。鉴于在人类中研究此类机制面临的挑战，需要能够重现人类肝细胞脂肪酸代谢的细胞模型。在这里，我们回顾了人类研究中关于膳食脂肪及其数量和组成如何导致IHTG积累的已知信息。我们还从细胞模型产生的数据中探讨了脂肪酸组成对肝细胞脂肪代谢的影响，以帮助解释体内研究中观察到的差异。
