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National Institute of Environmental Health Sciences

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Publication Detail

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

Authors: Larsen, Michele Campaigne; Bushkofsky, Justin R; Gorman, Tyler; Adhami, Vaqar; Mukhtar, Hasan; Wang, Suqing; Reeder, Scott B; Sheibani, Nader; Jefcoate, Colin R

Published In Arch Biochem Biophys, (2015 Apr 01)

Abstract: 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.

PubMed ID: 25703193 Exiting the NIEHS site

MeSH Terms: Adiposity; Age Factors; Animals; Cytochrome P-450 CYP1B1/genetics; Cytochrome P-450 CYP1B1/metabolism*; Diabetes Mellitus, Type 2/genetics; Diabetes Mellitus, Type 2/metabolism; Dietary Fats/administration & dosage; Energy Metabolism; Fatty Acids/metabolism*; Fatty Liver/genetics; Fatty Liver/metabolism; Female; Gene Expression Profiling; Homeostasis; Leptin/metabolism; Liver/metabolism*; Male; Mice, Inbred C57BL; Mice, Knockout; Obesity/genetics; Obesity/metabolism; Oxidative Stress; PPAR alpha/genetics; PPAR alpha/metabolism; Stearoyl-CoA Desaturase/genetics; Stearoyl-CoA Desaturase/metabolism

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