The ins and outs of liver fat metabolism: The effect of phenotype and diet on risk of intrahepatic triglyceride accumulation

Abstract 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...

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Main Authors: Kieran Smith, Kaitlyn M. J. H. Dennis, Leanne Hodson
Format: Article
Language:English
Published: Wiley 2025-07-01
Series:Experimental Physiology
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Online Access:https://doi.org/10.1113/EP092001
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author Kieran Smith
Kaitlyn M. J. H. Dennis
Leanne Hodson
author_facet Kieran Smith
Kaitlyn M. J. H. Dennis
Leanne Hodson
author_sort Kieran Smith
collection DOAJ
description Abstract 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.
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spelling doaj-art-e8a6d8c9d01f431493877685d4f00b812025-08-20T03:15:54ZengWileyExperimental Physiology0958-06701469-445X2025-07-01110793694810.1113/EP092001The ins and outs of liver fat metabolism: The effect of phenotype and diet on risk of intrahepatic triglyceride accumulationKieran Smith0Kaitlyn M. J. H. Dennis1Leanne Hodson2Oxford Centre for Diabetes, Endocrinology and Metabolism University of Oxford Oxford UKOxford Centre for Diabetes, Endocrinology and Metabolism University of Oxford Oxford UKOxford Centre for Diabetes, Endocrinology and Metabolism University of Oxford Oxford UKAbstract 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.https://doi.org/10.1113/EP092001dietary macronutrientsfatty acidshepatichuman physiologyliver fatphenotype
spellingShingle Kieran Smith
Kaitlyn M. J. H. Dennis
Leanne Hodson
The ins and outs of liver fat metabolism: The effect of phenotype and diet on risk of intrahepatic triglyceride accumulation
Experimental Physiology
dietary macronutrients
fatty acids
hepatic
human physiology
liver fat
phenotype
title The ins and outs of liver fat metabolism: The effect of phenotype and diet on risk of intrahepatic triglyceride accumulation
title_full The ins and outs of liver fat metabolism: The effect of phenotype and diet on risk of intrahepatic triglyceride accumulation
title_fullStr The ins and outs of liver fat metabolism: The effect of phenotype and diet on risk of intrahepatic triglyceride accumulation
title_full_unstemmed The ins and outs of liver fat metabolism: The effect of phenotype and diet on risk of intrahepatic triglyceride accumulation
title_short The ins and outs of liver fat metabolism: The effect of phenotype and diet on risk of intrahepatic triglyceride accumulation
title_sort ins and outs of liver fat metabolism the effect of phenotype and diet on risk of intrahepatic triglyceride accumulation
topic dietary macronutrients
fatty acids
hepatic
human physiology
liver fat
phenotype
url https://doi.org/10.1113/EP092001
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