Liver tissue lipids in metabolic dysfunction-associated steatotic liver disease with diabetes and obesity

• Published in: Clinics and research in hepatology and gastroenterology 2024-08, Vol.48 (7), p.102402, Article 102402
• Main Authors: Sourianarayanane, Achuthan, Brydges, Christopher R., McCullough, Arthur J
• Format: Article
• Language: English
• Subjects: Adult; Aged; Ceramides; Diabetes Mellitus - metabolism; Fatty Liver - complications; Fatty Liver - metabolism; Female; Humans; Lipid Metabolism; Lipidomics; Lipids - blood; Liver - metabolism; Male; MASH; MASLD; Middle Aged; NAFLD; Obesity - complications; Obesity - metabolism; Phospholipids
• ISSN: 2210-7401; 2210-741X; 2210-741X
• DOI: 10.1016/j.clinre.2024.102402

•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. 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. 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. 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. 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. [Display omitted]