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Liver tissue lipids in metabolic dysfunction-associated steatotic liver disease with diabetes and obesity - 27/06/24

Doi : 10.1016/j.clinre.2024.102402 
Achuthan Sourianarayanane a, , Christopher R. Brydges b, Arthur J McCullough c
a Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, WI 53226, USA 
b West Coast Metabolomics Center, University of California Davis, CA 95616, USA 
c Digestive Disease Institute, Cleveland Clinic, Cleveland, OH 44195, USA 

Corresponding author.

Highlights

Changes in liver tissue lipids occur in patients with MASLD without obesity or diabetes.
The presence of MASLD, obesity, has a similar effect (increase or decrease) on most lipid groups, but the degree of effect differs.
Diabetes mellitus produces changes in liver tissue lipids, which are different from the effects of obesity.
Step-wise changes in different lipid groups are seen with MASLD and increased metabolic risks.
The combined effect of MASLD, obesity, and diabetes on liver tissue lipids may be cumulative but not additive.

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Abstract

Background

Diabetes and obesity are associated with altered lipid metabolism and hepatic steatosis. Studies suggest that increases in lipid accumulation in these patients with metabolic dysfunction-associated steatotic liver disease (MASLD) are not uniform for all lipid components. This study evaluates this variation.

Methods

A comprehensive lipidomic analysis of different lipid groups, were performed on liver tissue and plasma samples obtained at the time of histology from a well-defined cohort of 72 MASLD participants. The lipid profiles of controls were compared to those of MASLD patients with obesity, diabetes, or a combination of both.

Results

MASLD patients without obesity or diabetes exhibited distinct changes in the lipid profile of their liver tissue. The presence of diabetes or obesity further modified these lipid profiles (e.g., ceramide 47:7;4O), with positive or negative correlation (p < 0.05). A step-wise increase (long-chain fatty acids, triglycerides, and ceramides) or decrease (ultra-long fatty acids, diglycerides, and phospholipids) for lipid groups was observed compared to control among patients with MASLD without obesity or diabetes to MASLD patients with obesity as a single risk factor, and MASLD patients with obesity and diabetes. Changes in lipids observed in the plasma did not align with their corresponding liver tissue findings.

Conclusion

The changes observed in the composition of lipids are not similar in patients with obesity and diabetes among those with MASLD. This highlights the different metabolic processes at play. The presence of obesity or diabetes in patients with MASLD exacerbates these lipid derangements, underscoring the potential for targeted intervention in MASLD patients.

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Graphical abstract




Image, graphical abstract

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Keywords : Lipidomics, MASLD, NAFLD, MASH, Ceramides, Phospholipids

Abbreviations : ALT, ANOVA, ANI, BMI, Cer, LPC, MASL, MASLD, MASH, M-Control, M-DM, M-O, M-O+DM, NAFLD, PC, PE, PI, PS


Mappa


 Address for reprints if different from that of the corresponding author, as above, Approval of the research protocol: The study was approved by the local Institutional Review Board of the Medical College of Wisconsin (PRO 27669 and PRO 41131, respectively).


© 2024  Elsevier Masson SAS. Tutti i diritti riservati.
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Vol 48 - N° 7

Articolo 102402- Agosto 2024 Ritorno al numero
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