Researchers at Chiba University have identified that hyodeoxycholic acid (HDCA) can reduce liver fat in mice without inducing weight loss. As reported by HCPLive, the study published in Cell Reports demonstrates that a 0.25% dose of HDCA lowers hepatic triglyceride content, improves liver function, and reduces blood glucose levels in mice fed a high-fat diet while their body weight remains unchanged.
Chiba University Researchers Link HDCA to PPARα Activation
The research team, collaborating with the University of Cambridge, began the project after noticing that adipose tissue transplantation increased circulating HDCA levels in their diabetic mouse model. Takashi Miki, MD, PhD, dean of the Graduate School of Medicine at Chiba University and lead investigator, stated that this observation prompted the team to investigate the metabolic effects of the bile acid. The study found that HDCA’s efficacy relies on peroxisome proliferator-activated receptor α (PPARα), a nuclear receptor responsible for activating genes that break down fatty acids in the liver. In experiments where mice lacked PPARα, HDCA failed to produce the same metabolic improvements.
Immune and Hormonal Pathways Influence Liver Fat
The study identified two distinct pathways through which HDCA reaches and activates PPARα. First, HDCA increases the population of invariant natural killer T (iNKT) cells in the liver, which subsequently release interferon-γ to trigger PPARα. Second, the bile acid raises levels of glucagon-like peptide-1 (GLP-1), a gut hormone. The research confirmed that the beneficial effects of HDCA disappeared in mice lacking the GLP-1 receptor, highlighting the role of this hormonal signaling in regulating liver fat metabolism.
Metabolic Research Questions
- Did this study involve human participants?
- No, this project was conducted using mouse models of diabetes and high-fat diet-induced metabolic dysfunction.
- Why is the lack of weight loss significant in this study?
- The authors noted that the reduction in liver fat was not a byproduct of weight loss, which suggests that HDCA works through specific metabolic pathways rather than simply reducing body mass.
- How did the researchers confirm the role of PPARα?
- The investigators tested the bile acid in mice that lacked the PPARα receptor and observed that the therapeutic effects on liver fat and blood glucose were no longer present.
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