The role of hepatic lipid composition in obesity-related metabolic disease

Willis, Scott A.; Bawden, Stephen; Malaikah, Sundus; Sargeant, Jack A.; Stensel, David J.; Aithal, Guruprasad P.; King, James A.

Abstract

Obesity is a primary antecedent to non-alcoholic fatty liver disease whose cardinal feature is excessive hepatic lipid accumulation. Although total hepatic lipid content closely associates with hepatic and systemic metabolic dysfunction, accumulating evidence suggests that the composition of hepatic lipids may be more discriminatory. This review summarises cross-sectional human studies using liver biopsy/lipidomics and proton magnetic resonance spectroscopy to characterise hepatic lipid composition in people with obesity and related metabolic disease. A comprehensive literature search identified 26 relevant studies published up to 31st March 2021 which were included in the review. The available evidence provides a consistent picture showing that people with hepatic steatosis possess elevated saturated and/or monounsaturated hepatic lipids and a reduced proportion of polyunsaturated hepatic lipids. This altered hepatic lipid profile associates more directly with metabolic derangements, such as insulin resistance, and may be exacerbated in non-alcoholic steatohepatitis. Further evidence from lipidomic studies suggests that these deleterious changes may be related to defects in lipid desaturation and elongation, and an augmentation of the de novo lipogenic pathway. These observations are consistent with mechanistic studies implicating saturated fatty acids and associated bioactive lipid intermediates (ceramides, lysophosphatidylcholines and diacylglycerol) in the development of hepatic lipotoxicity and wider metabolic dysfunction, whilst monounsaturated fatty acids and polyunsaturated fatty acids may exhibit a protective role. Future studies are needed to prospectively determine the relevance of hepatic lipid composition for hepatic and non-hepatic morbidity and mortality; and to further evaluate the impact of therapeutic interventions such as pharmacotherapy and lifestyle interventions.

Citation

Willis, S. A., Bawden, S., Malaikah, S., Sargeant, J. A., Stensel, D. J., Aithal, G. P., & King, J. A. (2021). The role of hepatic lipid composition in obesity-related metabolic disease. Liver International, 41(12), 2819-2835. https://doi.org/10.1111/liv.15059

• Journal Article Type: Review
• Acceptance Date: Sep 17, 2021
• Online Publication Date: Sep 27, 2021
• Publication Date: Dec 1, 2021
• Deposit Date: Sep 23, 2021
• Publicly Available Date: Sep 28, 2022
• Journal: Liver International
• Print ISSN: 1478-3223
• Electronic ISSN: 1478-3231
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 41
• Issue: 12
• Pages: 2819-2835
• DOI: https://doi.org/10.1111/liv.15059
• Keywords: Liver, fatty acid, quality, non-alcoholic fatty liver disease, ectopic fat, insulin resistance
• Public URL: https://nottingham-repository.worktribe.com/output/6296645
• Publisher URL: https://onlinelibrary.wiley.com/doi/10.1111/liv.15059?af=R
• Additional Information: This is the peer reviewed version of the following article: Willis, S.A., Bawden, S., Malaikah, S., Sargeant, J.A., Stensel, D.J., Aithal, G.P. and King, J.A. (2021), The role of hepatic lipid composition in obesity-related metabolic disease. Liver International., which has been published in final form at https://doi.org/10.1111/liv.15059. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.