Smith Kieran, Dennis Kaitlyn M J H, Hodson Leanne
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
Oxford NIHR Biomedical Research Centre, Churchill Hospital, Oxford, UK.
Exp Physiol. 2025 Jul;110(7):936-948. doi: 10.1113/EP092001. Epub 2025 Jan 24.
In health, the liver is a metabolically flexible organ that plays a key role in regulating systemic lipid and glucose concentrations. There is a constant flux of fatty acids (FAs) to the liver from multiple sources, including adipose tissue, dietary, endogenously synthesized from non-lipid precursors, intrahepatic lipid droplets and recycling of triglyceride-rich remnants. Within the liver, FAs are used for triglyceride synthesis, which can be oxidized, stored or secreted in very low-density lipoproteins into the systemic circulation. The processes of FA uptake, FA synthesis and the intracellular partitioning of FAs into storage, oxidation or secretory pathways are tightly regulated. An imbalance in these processes causes intrahepatic triglyceride to accumulate and is associated with the development of metabolic dysfunction-associated steatotic liver disease. It is well appreciated that many factors can influence intrahepatic FA partitioning, and although there is good evidence that both phenotype (e.g., sex, ethnicity and adiposity) and dietary macronutrient composition can play a role in intrahepatic triglyceride accumulation, their interaction remains poorly understood. The aim of this review is to explore how the respective pathways of FA delivery, synthesis and disposal are altered by phenotype and understand how dietary macronutrient composition might influence the partitioning of FAs in the liver in vivo, in humans.
在健康状态下，肝脏是一个代谢灵活的器官，在调节全身脂质和葡萄糖浓度方面发挥着关键作用。脂肪酸（FAs）从多个来源持续流入肝脏，这些来源包括脂肪组织、饮食、由非脂质前体在内源性合成、肝内脂质滴以及富含甘油三酯的残余物的再循环。在肝脏内，脂肪酸用于甘油三酯合成，甘油三酯可被氧化、储存或分泌到极低密度脂蛋白中进入体循环。脂肪酸摄取、脂肪酸合成以及脂肪酸在细胞内分配到储存、氧化或分泌途径的过程受到严格调控。这些过程的失衡会导致肝内甘油三酯积累，并与代谢功能障碍相关脂肪性肝病的发展有关。众所周知，许多因素会影响肝内脂肪酸分配，尽管有充分证据表明表型（如性别、种族和肥胖）和饮食常量营养素组成都可能在肝内甘油三酯积累中起作用，但它们之间的相互作用仍知之甚少。本综述的目的是探讨表型如何改变脂肪酸输送、合成和处置的各自途径，并了解饮食常量营养素组成如何可能在体内影响人类肝脏中脂肪酸的分配。
