Cytochrome P450 1B1: An unexpected modulator of liver fatty acid homeostasis.

Autor: Larsen MC; Department of Cell and Regenerative Biology, University of Wisconsin, Madison, WI 53706, United States., Bushkofsky JR; Molecular and Environmental Toxicology Center, University of Wisconsin, Madison, WI 53706, United States; Endocrinology and Reproductive Physiology Program, University of Wisconsin, Madison, WI 53706, United States., Gorman T; Department of Cell and Regenerative Biology, University of Wisconsin, Madison, WI 53706, United States., Adhami V; Department of Dermatology, University of Wisconsin, Madison, WI 53706, United States., Mukhtar H; Department of Dermatology, University of Wisconsin, Madison, WI 53706, United States., Wang S; Department of Cell and Regenerative Biology, University of Wisconsin, Madison, WI 53706, United States., Reeder SB; Department of Radiology, University of Wisconsin, Madison, WI 53706, United States; Department of Medical Physics, University of Wisconsin, Madison, WI 53706, United States; Department of Biomedical Engineering, University of Wisconsin, Madison, WI 53706, United States; Department of Medicine, University of Wisconsin, Madison, WI 53706, United States; Department of Emergency Medicine, University of Wisconsin, Madison, WI 53706, United States., Sheibani N; Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI 53706, United States., Jefcoate CR; Department of Cell and Regenerative Biology, University of Wisconsin, Madison, WI 53706, United States; Molecular and Environmental Toxicology Center, University of Wisconsin, Madison, WI 53706, United States; Endocrinology and Reproductive Physiology Program, University of Wisconsin, Madison, WI 53706, United States. Electronic address: jefcoate@wisc.edu.
Jazyk: angličtina
Zdroj: Archives of biochemistry and biophysics [Arch Biochem Biophys] 2015 Apr 01; Vol. 571, pp. 21-39. Date of Electronic Publication: 2015 Feb 20.
DOI: 10.1016/j.abb.2015.02.010
Abstrakt: Cytochrome P450 1b1 (Cyp1b1) expression is absent in mouse hepatocytes, but present in liver endothelia and activated stellate cells. Increased expression during adipogenesis suggests a role of Cyp1b1 metabolism in fatty acid homeostasis. Wild-type C57BL/6j (WT) and Cyp1b1-null (Cyp1b1-ko) mice were provided low or high fat diets (LFD and HFD, respectively). Cyp1b1-deletion suppressed HFD-induced obesity, improved glucose tolerance and prevented liver steatosis. Suppression of lipid droplets in sinusoidal hepatocytes, concomitant with enhanced glycogen granules, was a consistent feature of Cyp1b1-ko mice. Cyp1b1 deletion altered the in vivo expression of 560 liver genes, including suppression of PPARγ, stearoyl CoA desaturase 1 (Scd1) and many genes stimulated by PPARα, each consistent with this switch in energy storage mechanism. Ligand activation of PPARα in Cyp1b1-ko mice by WY-14643 was, nevertheless, effective. Seventeen gene changes in Cyp1b1-ko mice correspond to mouse transgenic expression that attenuated diet-induced diabetes. The absence of Cyp1b1 in mouse hepatocytes indicates participation in energy homeostasis through extra-hepatocyte signaling. Extensive sexual dimorphism in hepatic gene expression suggests a developmental impact of estrogen metabolism by Cyp1b1. Suppression of Scd1 and increased leptin turnover support enhanced leptin participation from the hypothalamus. Cyp1b1-mediated effects on vascular cells may underlie these changes.
(Copyright © 2015 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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