(P15-001-24) Protective Effects of Curcumin in Metabolic Dysfunction-Associated Steatotic Liver Disease

Objectives: To determine the mechanisms by which curcumin reduced hepatic steatosis and inflammation in this model.

Methods: Five-week-old male B6 mice were randomly divided into either high fat diet (HF, 45% kcal fat) or HF diet supplemented with curcumin (HFC, 0.4% w/w curcumin) and fed these diets for 14 weeks. At study termination, liver tissues were collected for protein and RNA isolation and analyses of gene (by qPCR and RNA Seq) and protein expression (by western blotting), respectively. Gene and protein results were analyzed using GraphPad Prism Software 8.2. RNA-Seq data were normalized and differentially expressed genes were statistically analyzed and used for Ingenuity Pathway Analysis IPA® software (v6.0, QIAGEN, Redwood City, CA, USA).

Results: Curcumin reduced liver triglyceride levels (p < 0.05), compared to HF fed mice. Curcumin also shows a trend of reduced expression of inflammation and lipid metabolizing genes in liver, though not significant, such as Interleukin-6 (p >0.05), acetyl CoA carboxylase (p >0.05), and fatty acid synthase(p >0.05). Curcumin was able to significantly reduce toll-like receptor-4 (p < 0.05). Transcriptome sequencing revealed 631 differentially expressed genes, with 263 downregulated and 368 upregulated genes. Curcumin increased fatty acid-beta oxidation, and the transcriptional regulator PPAR alpha, and downregulated LPS/IL-1 mediated inhibition of RXR pathways. Additional analyses are ongoing for validation of these mRNAs using PCR and western blotting.

Conclusions: Our results suggest a therapeutic potential of curcumin in reducing obesity and liver steatosis and inflammation, via specific metabolic pathways. Ongoing studies will determine direct effects of curcumin in liver and hepatoma cells and will further analyze the curcumin metabolites that may be mediating curcumin effects.

Funding Sources: American Heart Association