Hepatocyte peroxisome biogenesis and phytol-induced metabolic stress in liver disease

Author

• William GallowayFollow

Date of Award

2026

Degree Name

Biomedical Research

College

Joan C. Edwards School of Medicine

Type of Degree

M.S.

Document Type

Thesis

First Advisor

Dr. Yongke Lu

Second Advisor

Dr. Jinju Wang

Third Advisor

Dr. Jung Kim

Abstract

Hepatocyte peroxisomes are required for metabolism of phytol-derived branched-chain fatty acids through the ACOX2-SCPx beta-oxidation pathway. This study tests whether hepatocyte-specific deletion of PEX16 (Pex16^Alb-Cre), which eliminates peroxisome biogenesis, sensitizes the liver to phytol-induced injury. The Pex16^Alb-Cre mice and their normal control Pex16^fl/fl mice were fed the Lieber-DeCarli liquid with or without 0.1 percent phytol for eight weeks. Serum alanine aminotransferase (ALT) and liver index were measured. Liver sections were stained with hematoxylin and eosin and Masson’s trichrome. Immunoblot analysis of peroxisomal enzyme expression was also performed. Phytol had no effect in Pex16^fl/fl mice as serum ALT liver size and liver histology were unchanged. In Pex16^Alb-Cre mice fed phytol, serum ALT and liver index rose significantly. Histology showed hepatocellular disarray, vacuolization, and periportal collagen deposition in phytol-treated Pex16^Alb-Cre mice. Immunoblot analysis indicated that phytol induced peroxisomal ACOX1-thiolase pathway but not ACOX2-SCPx pathway, and more importantly, the ACOX1-thiolase pathway was upregulated, but ACOX2-SCPx pathway was downregulated in the Pex16^Alb-Cre mice, which might be responsible for the phytol-induced liver injury in the Pex16^Alb-Cre mice but not in the Pex16fl/fl mice. These results establish that dietary phytol is hepatotoxic when peroxisomal branched-chain fatty acid oxidation is lost and suggest that dietary phytol intake may be an underappreciated risk factor in patients with peroxisomal dysfunction.

Subject(s)

Medical sciences.

Biochemistry.

Cytology.

Physiology.

Medicine -- Research.

Peroxisomes.

Liver cells.

Liver -- Diseases.

Metabolism.

Life -- Origin.

Recommended Citation

Galloway, William, "Hepatocyte peroxisome biogenesis and phytol-induced metabolic stress in liver disease" (2026). Theses, Dissertations and Capstones. 2062.
https://mds.marshall.edu/etd/2062