Elevated stearoyl-CoA desaturase 1 activity is associated with alcohol-associated liver disease

• Published in: Alcohol (Fayetteville, N.Y.) N.Y.), 2022-08, Vol.102, p.51-57
• Main Authors: Klepp, T.D., Sloan, M.E., Soundararajan, Soundarya, Ramsden, C.E., Cinar, R., Schwandt, M.L., Diazgranados, N., Vatsalya, V., Ramchandani, V.A.
• Format: Article
• Language: English
• Subjects: Alanine; Alanine transaminase; Alcohol use; alcohol use disorder; alcohol-associated liver disease; Binge Drinking; Body mass index; Desaturase; Drinking behavior; Fatty Acids; Fatty Liver; Gas chromatography; Hepatitis; Humans; Lipids; Liver; Liver diseases; Liver Diseases, Alcoholic; Mass spectroscopy; Mediation; Palmitic acid; Palmitoleic acid; Plasma; Regression analysis; Stearoyl-CoA desaturase; Stearoyl-CoA Desaturase - metabolism; Transaminase
• ISSN: 0741-8329; 1873-6823
• DOI: 10.1016/j.alcohol.2022.04.001

Chronic binge drinking induces hepatic lipid accumulation, but only certain individuals develop alcohol-associated liver disease (ALD). Specific patterns of lipid accumulation are thought to be associated with ALD, but this has not been comprehensively investigated to date. We analyzed plasma fatty acid levels, quantified by gas chromatography-mass spectrometry, in a sample of patients with alcohol use disorder (AUD). Given that elevation in serum alanine transaminase (ALT) levels are strongly associated with ALD, patients were stratified into two groups based on ALT levels: an ALD group (ALT >40 IU/L) and a non-ALD group (ALT ≤40 IU/L). There was a shift toward greater concentrations of monounsaturated fatty acids in the ALD group compared to the non-ALD group. Stearoyl-CoA desaturase (SCD1) activity in the ALD group was then estimated as the ratio of palmitoleic acid (16:1) to palmitic acid (16:0). SCD1 activity was greater in the ALD than the non-ALD group. A series of linear regression models demonstrated that SCD1 activity mediated the association between binge drinking and ALD. These findings provide initial evidence that SCD1 activity may be associated with ALD. If validated prospectively, elevated SCD1 activity could potentially be used as a biomarker to identify individuals at high risk for developing ALD. •Binge drinking frequency was associated with alanine transaminase, a marker of alcohol-associated liver disease (ALD).•Stearoyl-CoA desaturase 1 (SCD1) activity (palmitoleic acid to palmitic acid ratio) was significantly elevated in ALD.•SCD1 activity mediated the association between binge drinking frequency and ALD.