1588-P: Galectin-3 Inhibitor Protect ApoE Knockout Mice against Metabolic Dysfunction–Associated Steatohepatitis

Metabolic-dysfunction associated steatohepatitis is characterized by steatosis, inflammatory infiltrate and hepatocellular ballooning, and it can present fibrosis. The aim of work was to evaluate the effect of modified citrus pectin (MCP), inhibitor of galectin-3, in ApoE KO mice fed a western diet (WD). ApoE KO mice were divided into 3 groups: standard diet-fed (SD) group, WD-fed group, and WD-fed + MCP-treated group (WD+MCP). MCP treatment inhibited the increase of glucose tolerance, glycemia, plasma insulin and HOMA-IR, when compared to WD group. MCP treatment was able to inhibit the increase of TAG in the tissue by 9%, plasma TAG and VLDL, however had no significant difference for cholesterol and fatty acids in relation to WD group. We analyzed the expression of genes involved in the lipogenesis pathway in the liver (SREBP1, ACC, SCD1 and FASn). Only ACC gene expression was increased by 10x and SREBP1 protein expression by 183% in the WD group compared to the SD group. And the MCP treatment inhibited the increase of both. We also analyzed the collagen deposition and expression of genes involved in the collagen production (TGF-Beta, Col1alpha, MMP2), and MCP treatment inhibited the increase in collagen deposition by 8.2% and only MMP2 gene expression. The inflammatory profile of the liver was also shown, MCP treatment inhibited the increase of expression of F4/80, gene expression of cytokines (TNFa, IL-1b) and pJNK protein activity. We concluded that galectin-3 inhibition by the treatment with MCP protects ApoE KO mice against the development of MASH and insulin resistance