1578-P: Recombinant Decorin Improves Features of Diabetes-Related Steatotic Liver Disease in Mice

• DOI: 10.2337/db24-1578-p
• Publication Date: 2024-06-14T06:50:19Z
• Authors: BEDAIR DEWIDAR; ASLIHAN YAVAS; CESARE GRANATA; NINA TRINKS; LUCIA MASTROTOTARO; IRENE ESPOSITO; MICHELLE REINADOF...; MICHAEL RODEN
• Keywords: Steatosis; Steatohepatitis; Liver disease

Although type 2 diabetes closely associates with metabolic dysfunction-associated steatotic liver disease (MASLD) and accelerates its progression to steatohepatitis (MASH), fibrosis hepatocellular carcinoma (HCC), still no treatment has been approved for MASLD. The extracellular matrix proteoglycan, decorin (DCN) may protect against HCC, but role in MASLD is yet unclear. Thus, we treated mice 8 w recombinant human DCN (200 μg/kg/day) or phosphate-buffered saline (PBS) via subcutaneous osmotic pumps. Diabetes-related MASH was induced by injecting two-day old male C57BL/6j 200 µg streptozotocin subsequent feeding a high-fat diet from 4 on. Control (CTRL) received vehicle standard diet. Hepatic steatosis, inflammation, ballooning, were quantified histology. Liver mitochondrial respiration ROS assessed high-resolution respirometry. Plasma metabolites protein gene expression levels colorimetric assays, ELISA qPCR. PBS showed greater hepatic steatosis along 3.28fold rise blood glucose as compared CTRL (p<0.01). DCN, not reversed diabetic (p<0.001 p>0.05 vs CTRL). Median score of ballooning lower than (p<0.05). Compared PBS, lowered genes involved lipid synthesis, e. g. Fasn Srebf, increased plasma HDL-cholesterol. also downregulated specific inflammation- fibrogenesis-related genes, Il6 Tgfβ (both p<0.05 PBS). DCN-treated livers fatty acid oxidation-linked reduced production In conclusion, improves biomarkers cellular injury MASH, likely enhancing capacity, therefore represent promising concept treating diabetes. Disclosure B. Dewidar: None. A. Yavas: C. Granata: N. Trinks: L. Mastrototaro: I. Esposito: M. ReinaDoFundo: Roden: Advisory Panel; Eli Lilly Company. Research Support; Boehringer-Ingelheim. Novo Nordisk. TARGET PharmaSolutions, Inc. Speaker's Bureau; AstraZeneca. Funding German Center Diabetes (82DZD02E1G)