DOI: 10.1097/mol.0000000000000933 ISSN: 0957-9672

Altered lipid metabolism and the development of metabolic-associated fatty liver disease

Christy Foster, Charles A. Gagnon, Ambika P. Ashraf
  • Cell Biology
  • Cardiology and Cardiovascular Medicine
  • Nutrition and Dietetics
  • Genetics
  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism
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Purpose of review

An increasing amount of research has underscored the significant role of lipoproteins in the pathogenesis of metabolic-associated fatty liver disease (MAFLD). This comprehensive review examines the intricate relationship between lipoprotein abnormalities and the development of MAFLD.

Recent findings

Atherogenic dyslipidemia seen in insulin resistance states play a significant role in initiating and exacerbating hepatic lipid accumulation. There are also specific genetic factors (PNPLA3, TM6SF2, MBOAT7, HSD17B13, GCKR-P446L) and transcription factors (SREBP-2, FXR, and LXR9) that increase susceptibility to both lipoprotein disorders and MAFLD. Most monogenic primary lipid disorders do not cause hepatic steatosis unless accompanied by metabolic stress. Hepatic steatosis occurs in the presence of secondary systemic metabolic stress in conjunction with predisposing environmental factors that lead to insulin resistance. Identifying specific aberrant lipoprotein metabolic factors promoting hepatic fat accumulation and subsequently exacerbating steatohepatitis will shed light on potential targets for therapeutic interventions.

Summary

The clinical implications of interconnection between genetic factors and an insulin resistant environment that predisposes MAFLD is many fold. Potential therapeutic strategies in preventing or mitigating MAFLD progression include lifestyle modifications, pharmacological interventions, and emerging therapies targeting aberrant lipoprotein metabolism.

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