Organ specificity of beta-carotene induced lung gene-expression changes in Bcmo1−/− mice
Correspondence: Professor Jaap Keijer, Department of Human and Animal Physiology, Wageningen University, P. O. Box 338, 6700 AH Wageningen, The Netherlands
Whole genome transcriptome analysis of male and female beta-carotene 15,15′-monooxygenase knockout (Bcmo1−/−) and Bcmo1+/+ (wild-type) mice with or without 14 wk of BC supplementation was done. We previously showed that only 1.8% of the genes regulated by BC in lung were also regulated in liver and inguinal white adipose tissue (iWAT), suggesting lung specific responses. Here, we explicitly questioned the lung specificity.
Methods and results
We show that BC supplementation resulted in an opposite direction of gene-regulation in male compared to female Bcmo1−/− mice in lung, liver, and iWAT. This supports a systemic effect of BC on steroid hormone metabolism mediated responses. Lung, liver, and iWAT of female Bcmo1−/− mice showed an increased inflammatory response, which was counteracted by supplementation of BC. This supports a genotype dependent increased sensitivity of female mice for vitamin A deficiency. Finally, the effect of BC on Wnt signaling in male Bcmo1−/− mice was examined. Frizzled homolog 6 (Fzd6) downregulation was seen in all three tissues. Collagen triple helix containing 1 (Cthrc1) downregulation was seen in lung tissue only, suggesting specificity. Upregulation of genes involved in oxygen sensing was seen in lung and iWAT, while protocadherin upregulation was only seen in lung.
Our results demonstrate that effects of BC are strongly sex dependent. While effects of BC on hormone metabolism mediated responses and inflammation are systemic, effects on Wnt signaling may be lung specific.