RNA-seq analysis of hepatic transcriptomic changes in MASH mice treated with IP6 and INS

This study aimed to investigate the preventive effects of inositol hexakisphosphate (IP6) and inositol (INS) on metabolic dysfunction-associated steatohepatitis (MASH) induced by a western diet combined with low-dose CCl4 (WD/CCl4) in mice. Male C57BL/6J mice were randomly assigned to five groups: (1) Normal chow control (NC), (2) WD/CCl4 model (MASH), (3) IP6 preventive intervention (MASH+IP6), (4) INS preventive intervention (MASH+INS), and (5) Silymarin positive control (MASH+PC). After 10 weeks of intervention, hepatic tissues were collected for transcriptomic analysis.Metabolic phenotyping demonstrated that WD/CCl4 treatment resulted in increased body weight, liver index, fasting blood glucose, and glycated serum protein levels compared with NC mice. Preventive administration of IP6, INS, or silymarin significantly ameliorated these changes and improved glucose tolerance and insulin sensitivity, suggesting their ability to prevent obesity and insulin resistance in MASH mice.To elucidate the molecular mechanisms underlying these preventive effects, RNA sequencing was performed on liver tissues from the NC, WD/CCl4, IP6, and INS groups. The transcriptomic profiles were used to identify differentially expressed genes and pathways associated with lipid metabolism, inflammation, and insulin signaling.Overall Design:A total of 4 experimental groups were included for RNA sequencing:NC (Normal Chow Control) - mice fed a standard chow diet.WD/CCl4 (MASH model) - mice fed a western diet and administered low-dose CCl4 to induce MASH.WD/CCl4 + IP6 (IP6 group) - MASH mice preventively treated with inositol hexakisphosphate.WD/CCl4 + INS (INS group) - MASH mice preventively treated with inositol.Liver samples were collected after 10 weeks of intervention, and total RNA was extracted for library construction and sequencing using the Illumina platform.