100% Fish oil-based lipid emulsion inhibits hepatic stellate cell activation via suppression of the TGF-β1 autocrine signaling.

Intestinal failure-associated liver disease (IFALD) is a life-threatening complication of short bowel syndrome (SBS), characterized by cholestasis, hepatic steatosis, and hepatic fibrosis. Fish oil-based lipid emulsion (FO) has been demonstrated to ameliorate IFALD compared to soybean oil lipid emulsion (SO). However, the mechanisms underlying the beneficial effects of FO remain elusive. This study investigated the effects of FO on the activation of hepatic stellate cells (HSCs) that are primarily responsible for liver fibrosis by differentiating into fibroblasts in a transforming growth factor-β1 (TGF-β1) dependent manner. The human HSCs line LX-2 cells were stimulated with TGF-β1 in the presence of FO and SO. FO, but not SO, inhibited the degradation of lipid droplets induced by TGF-β1, suggesting that FO maintains HSCs in a quiescent state. Furthermore, FO suppressed LX-2 cell proliferation and partially abolished the autocrine regulation of TGF-β1 and subsequent activation of HSCs, as evidenced by the reduced expression of alpha-1 type I collagen (Col1a1) mRNA. These effects were specific to LX-2 and were not observed in the human hepatocellular carcinoma cell line HuH-7. The unique fatty acid composition of FO, characterized by high levels of long-chain polyunsaturated fatty acids with carbon chains of 20 or more, may contribute to its antifibrotic properties. These findings suggest that FO suppresses excessive HSCs activation while maintaining physiological functions, providing novel insights into the antifibrotic mechanisms of FO.