Title | Obesity Leads to Tissue, but not Serum Vitamin A Deficiency. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Trasino SE, Tang X-H, Jessurun J, Gudas LJ |
Journal | Sci Rep |
Volume | 5 |
Pagination | 15893 |
Date Published | 2015 Nov 02 |
ISSN | 2045-2322 |
Keywords | Adiposity, Animals, Diet, High-Fat, Fatty Liver, Liver, Male, Mice, Mice, Inbred C57BL, Mice, Obese, Obesity, Vitamin A, Vitamin A Deficiency |
Abstract | Obesity negatively affects multiple metabolic pathways, but little is known about the impact of obesity on vitamin A (VA)[retinol (ROL)], a nutrient that regulates expression of genes in numerous pathways essential for human development and health. We demonstrate that obese mice, generated from a high fat diet (HFD) or by genetic mutations (i.e., ob/ob; db/db), have greatly reduced ROL levels in multiple organs, including liver, lungs, pancreas, and kidneys, even though their diets have adequate VA. However, obese mice exhibit elevated serum VA. Organs from obese mice show impaired VA transcriptional signaling, including reductions in retinoic acid receptor (RARα, RARβ2 and RARγ) mRNAs and lower intracellular ROL binding protein Crbp1 (RBP1) levels in VA-storing stellate cells. Reductions in organ VA signaling in obese mice correlate with increasing adiposity and fatty liver (steatosis), while with weight loss VA levels and signaling normalize. Consistent with our findings in obese mice, we show that increasing severity of fatty liver disease in humans correlates with reductions in hepatic VA, VA transcriptional signaling, and Crbp1 levels in VA storing stellate cells. Thus, obesity causes a "silent" VA deficiency marked by reductions in VA levels and signaling in multiple organs, but not detected by serum VA. |
DOI | 10.1038/srep15893 |
Alternate Journal | Sci Rep |
PubMed ID | 26522079 |
PubMed Central ID | PMC4629132 |
Grant List | T32 CA062948 / CA / NCI NIH HHS / United States R01CA043796 / CA / NCI NIH HHS / United States R01DE010389 / DE / NIDCR NIH HHS / United States R01 CA043796 / CA / NCI NIH HHS / United States R01 DE010389 / DE / NIDCR NIH HHS / United States |