biostudies-literatureBradic IAustrian Science Fund FWF159575https://www.ebi.ac.uk/biostudies/studies/S-EPMC7618626biostudies-literatureUnknown1870(1)Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent liver pathology worldwide, closely associated with obesity and metabolic disorders. Increasing evidence suggests that macrophages play a crucial role in the development of MASLD. Several human studies have shown an inverse correlation between circulating lysosomal acid lipase (LAL) activity and MASLD. LAL is the sole enzyme known to degrade cholesteryl esters (CE) and triacylglycerols in lysosomes. Consequently, these substrates accumulate when their enzymatic degradation is impaired due to LAL deficiency (LALD). This study aimed to investigate the role of hepatic LAL activity and liver-resident macrophages (i.e., Kupffer cells (KC)) in MASLD. To this end, we analyzed lipid metabolism in hepatocyte-specific (heBiochimica et biophysica acta. Molecular and cell biology of lipidsFrom LAL-D to MASLD: Insights into the role of LAL and Kupffer cells in liver inflammation and lipid metabolism.PMC7618626W 1226F 7305P 32400DOC 31P 30882F 7301Kuentzel KBRainer SPirchheim ASchwarz BKratky DVujic NBradic ITrauner MLarsen MRfalseFrom LAL-D to MASLD: Insights into the role of LAL and Kupffer cells in liver inflammation and lipid metabolism.Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent liver pathology worldwide, closely associated with obesity and metabolic disorders. Increasing evidence suggests that macrophages play a crucial role in the development of MASLD. Several human studies have shown an inverse correlation between circulating lysosomal acid lipase (LAL) activity and MASLD. LAL is the sole enzyme known to degrade cholesteryl esters (CE) and triacylglycerols in lysosomes. Consequently, these substrates accumulate when their enzymatic degradation is impaired due to LAL deficiency (LALD). This study aimed to investigate the role of hepatic LAL activity and liver-resident macrophages (i.e., Kupffer cells (KC)) in MASLD. To this end, we analyzed lipid metabolism in hepatocyte-specific (he2025-01-01T00:00:00Z2025 Jan2026-06-19T04:58:36.75Z2026-06-19T03:07:02.24ZS-EPMC76186263948657310.1016/j.bbalip.2024.159575