Molecular mechanisms of metabolic associated fatty liver disease (MAFLD): functional analysis of lipid metabolism pathways

Olufunto O. Badmus; Sarah A. Hillhouse; Christopher D. Anderson; Terry D. Hinds; David E. Stec

doi:10.1042/CS20220572

Molecular mechanisms of metabolic associated fatty liver disease (MAFLD): functional analysis of lipid metabolism pathways

Olufunto O. Badmus, Sarah A. Hillhouse, Christopher D. Anderson, Terry D. Hinds, David E. Stec

Research output: Contribution to journal › Review article › peer-review

94 Scopus citations

Abstract

The metabolic-associated fatty liver disease (MAFLD) is a condition of fat accumulation in the liver in combination with metabolic dysfunction in the form of overweight or obesity and insulin resistance. It is also associated with an increased cardiovascular disease risk, including hypertension and atherosclerosis. Hepatic lipid metabolism is regulated by a combination of the uptake and export of fatty acids, de novo lipogenesis, and fat utilization by β-oxidation. When the balance between these pathways is altered, hepatic lipid accumulation commences, and long-term activation of inflammatory and fibrotic pathways can progress to worsen the liver disease. This review discusses the details of the molecular mechanisms regulating hepatic lipids and the emerging therapies targeting these pathways as potential future treatments for MAFLD.

Original language	English
Pages (from-to)	1347-1366
Number of pages	20
Journal	Clinical Science
Volume	136
Issue number	18
DOIs	https://doi.org/10.1042/CS20220572
State	Published - Sep 2022

Bibliographical note

Publisher Copyright:
© 2022 The Author(s).

Funding

This work was supported by the National Institutes of Health [grant numbers R01DK126884 (to D.E.S.) and R01DK121797 (to T.D.H.J.)]; the National Heart, Lung and Blood Institute [grant number P01HL05197-11 (to D.E.S.)]; and the National Institute of General Medical Sciences [grant number P20GM104357-02 (to D.E.S.)]. This work was supported by the National Institutes of Health [grant numbers R01DK126884 (to D.E.S.) and R01DK121797 (to T.D.H.J.)]; the National Heart, Lung and Blood Institute [grant number P01HL05197-11 (to D.E.S.)]; and the National Institute of General Medical Sciences [grant number P20GM104357-02 (to D.E.S.)]. Figure 2 was created by Matthew Hazzard at the University of Kentucky. Figures 3–5 were made using BioRender.com.

Funders	Funder number
National Institutes of Health (NIH)	R01DK126884, R01DK121797
National Heart, Lung, and Blood Institute (NHLBI)	P01HL05197-11
National Institute of General Medical Sciences	P20GM104357
University of Kentucky

ASJC Scopus subject areas

General Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1042/CS20220572

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title = "Molecular mechanisms of metabolic associated fatty liver disease (MAFLD): functional analysis of lipid metabolism pathways",

abstract = "The metabolic-associated fatty liver disease (MAFLD) is a condition of fat accumulation in the liver in combination with metabolic dysfunction in the form of overweight or obesity and insulin resistance. It is also associated with an increased cardiovascular disease risk, including hypertension and atherosclerosis. Hepatic lipid metabolism is regulated by a combination of the uptake and export of fatty acids, de novo lipogenesis, and fat utilization by β-oxidation. When the balance between these pathways is altered, hepatic lipid accumulation commences, and long-term activation of inflammatory and fibrotic pathways can progress to worsen the liver disease. This review discusses the details of the molecular mechanisms regulating hepatic lipids and the emerging therapies targeting these pathways as potential future treatments for MAFLD.",

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AU - Badmus, Olufunto O.

AU - Hillhouse, Sarah A.

AU - Anderson, Christopher D.

AU - Hinds, Terry D.

AU - Stec, David E.

PY - 2022/9

Y1 - 2022/9

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AB - The metabolic-associated fatty liver disease (MAFLD) is a condition of fat accumulation in the liver in combination with metabolic dysfunction in the form of overweight or obesity and insulin resistance. It is also associated with an increased cardiovascular disease risk, including hypertension and atherosclerosis. Hepatic lipid metabolism is regulated by a combination of the uptake and export of fatty acids, de novo lipogenesis, and fat utilization by β-oxidation. When the balance between these pathways is altered, hepatic lipid accumulation commences, and long-term activation of inflammatory and fibrotic pathways can progress to worsen the liver disease. This review discusses the details of the molecular mechanisms regulating hepatic lipids and the emerging therapies targeting these pathways as potential future treatments for MAFLD.

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JF - Clinical Science

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Molecular mechanisms of metabolic associated fatty liver disease (MAFLD): functional analysis of lipid metabolism pathways

Abstract

Bibliographical note

Funding

ASJC Scopus subject areas

UN SDGs

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