Study Identifies Bile Acid That May Reduce Excess Fat Accumulation in Liver - Video

A bile acid may help reduce liver fat, according to a preclinical study from Chiba University, Japan, published in Cell Reports.

Researchers investigated hyodeoxycholic acid (HDCA), a bile acid, in mice fed a high-fat diet. They found that treatment with 0.25% HDCA reduced blood glucose, lowered triglyceride accumulation in the liver, and improved liver function without changing body weight.

The researchers then examined how HDCA produced these effects. They found that it increased activity of PPARα, a protein that controls genes involved in fatty-acid breakdown. When mice lacked PPARα, HDCA could no longer prevent fat from accumulating in the liver, suggesting that this protein is central to its effects.

The study identified two pathways through which HDCA activated PPARα. First, HDCA increased invariant natural killer T (iNKT) cells in the liver. These immune cells produced more interferon-γ (IFN-γ), a signalling molecule that activated PPARα in liver cells and promoted fatty-acid breakdown.

Second, HDCA increased levels of GLP-1, a gut hormone involved in metabolism. GLP-1 signalling was necessary for HDCA to reduce liver fat. When mice lacked the GLP-1 receptor, HDCA no longer prevented fat accumulation.

Researchers also tested liraglutide, a GLP-1 receptor agonist used for type 2 diabetes. It reduced liver fat in normal mice and mice lacking iNKT cells, but not in mice lacking PPARα. This indicated that GLP-1 acts through PPARα without requiring iNKT cells.

Overall, the findings suggest HDCA may reduce hepatic steatosis through two distinct pathways—an immune pathway involving iNKT cells and IFN-γ, and a metabolic pathway involving GLP-1—with both ultimately activating PPARα.

However, the study was conducted in mice, so its findings cannot yet establish that HDCA is safe or effective for treating MASLD in humans. Clinical trials are needed to determine whether this pathway can lead to future treatment.

REFERENCE: Lee, E., et al. (2026). Hyodeoxycholic acid suppresses hepatic steatosis in a PPARα-dependent manner via distinct GLP-1- and iNKT cell-mediated pathways. Cell Reports. DOI: 10.1016/j.celrep.2026.117822.