# Lisosan G as a Modulator of Serum Lipid/Lipoprotein Changes, Lipid Metabolism and TGF-β1 Level in Neoplastic and Non-Neoplastic Liver Injury: A Rat Model Study

## TL;DR

This study shows that Lisosan G, a fermented wheat product, changes liver lipid levels and reduces TGF-β1 in injured rat livers, especially in cancer.

## Contribution

The paper reveals that Lisosan G modulates lipoprotein composition and TGF-β1 in liver injury, with stronger effects in neoplastic conditions.

## Key findings

- Lisosan G altered lipoprotein lipid profiles in a liver condition-dependent manner.
- Hepatic TGF-β1 levels were reduced in injured livers, most notably in neoplastic injury.
- Effects on lipids and TGF-β1 suggest Lisosan G may act differently under normal vs. diseased states.

## Abstract

Chronic liver injury disrupts blood lipid transport and activates inflammatory–fibrogenic signaling. Transforming growth factor β1 (TGF-β1) is a key mediator and Lisosan G (LG), a fermented wheat-derived nutraceutical, has been proposed to influence these processes. Seventy-two Wistar rats were assigned to healthy controls, with non-neoplastic (PH) or neoplastic liver injury (HCC; PH followed by diethylnitrosamine), and fed a standard diet or the same diet supplemented with 2.5% or 5% LG. Plasma lipoproteins (VLDL, LDL, HDL1, HDL2) were isolated to measure cholesterol, phospholipids, and triacylglycerols, and TGF-β1 in liver was quantified by ELISA. LG responses were liver-status-dependent. In healthy rats, LG caused selective changes, including higher VLDL triacylglycerols and non-linear changes in cholesterol distribution across LDL and HDL subfractions. After PH, LG lowered VLDL phospholipids, raised VLDL triacylglycerols, and increased LDL cholesterol at 5% LG, with marked changes in HDL1/HDL2 cholesterol partitioning. In HCC, LG produced the strongest remodeling, with dose-related increases in LDL-associated lipids, increased HDL1 cholesterol, and decreased HDL2 cholesterol. Hepatic TGF-β1 rose after PH and peaked in HCC; LG reduced it in injured liver, especially in HCC. Overall, LG supplementation was associated with liver-status-dependent changes in lipoprotein lipids and reduced hepatic TGF-β1 abundance in injured liver. Mechanistic studies are needed to distinguish effects on secretion versus clearance and to assess pathway-level TGF-β signaling.

Chronic liver injury is accompanied by coordinated disturbances in lipid trafficking and inflammatory–fibrogenic signaling. Transforming growth factor beta 1 (TGF-β1) signaling has been implicated in hepatic fibrogenesis and tumor-associated remodeling and may co-vary with disturbances in lipid trafficking. Lisosan G (LG), a fermented wheat-derived nutraceutical, has reported antioxidant and anti-inflammatory activity and may influence these interconnected pathways. This study evaluated whether dietary LG alters the lipid composition of plasma lipoprotein fractions and hepatic TGF-β1 levels across distinct liver contexts. Seventy-two female Wistar rats were randomized into nine groups (n = 8/group) defined by liver condition, consisting of healthy control (Control), non-neoplastic liver (PH), and neoplastic liver injury (HCC; PH followed by diethylnitrosamine, DEN), and diet (standard diet, SD + 2.5% LG, or SD + 5% LG). Plasma lipoproteins (VLDL, LDL, HDL1, HDL2) were isolated by stepwise KBr density-gradient ultracentrifugation, and cholesterol (TC), phospholipids (PL), and triacylglycerols (TG) were quantified in each fraction. Hepatic TGF-β1 was measured by ELISA and normalized to total protein. LG effects depended strongly on baseline liver status, with significant Condition × Diet interactions for most lipid endpoints and for hepatic TGF-β1. In healthy rats, LG produced fraction-selective remodeling rather than uniform lipid lowering, including increased VLDL-TG at both doses and non-linear changes in cholesterol distribution across LDL and HDL subfractions. After PH, LG broadened lipid remodeling, including reduced VLDL-PL, increased VLDL-TG (both doses), and an increase in LDL-TC at 5% LG, accompanied by marked changes in HDL1/HDL2 cholesterol partitioning. In HCC, LG induced pronounced, often dose-dependent increases in LDL-associated lipids (LDL-PL, LDL-TG, LDL-TC) and increased HDL1-TC while decreasing HDL2-TC. Hepatic TGF-β1 was elevated in PH and further increased in HCC versus controls; LG reduced hepatic TGF-β1 in a condition-dependent manner, with the strongest reduction at 5% LG in HCC. Dietary Lisosan G remodels circulating lipoprotein lipid composition in a liver-status-dependent manner and is associated with reduced hepatic TGF-β1 abundance in injured liver, most prominently in neoplastic injury. These findings are consistent with the notion that nutraceutical interventions may show stronger phenotypic effects under perturbed metabolic–fibrogenic states than under stable physiology, while highlighting the need for mechanistic work to distinguish altered lipoprotein secretion from changes in peripheral clearance and to assess pathway-level TGF-β signaling.