Obesity Leads to Tissue, but not Serum Vitamin A Deficiency.

TitleObesity Leads to Tissue, but not Serum Vitamin A Deficiency.
Publication TypeJournal Article
Year of Publication2015
AuthorsTrasino SE, Tang X-H, Jessurun J, Gudas LJ
JournalSci Rep
Volume5
Pagination15893
Date Published2015 Nov 02
ISSN2045-2322
KeywordsAdiposity, 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.

DOI10.1038/srep15893
Alternate JournalSci Rep
PubMed ID26522079
PubMed Central IDPMC4629132
Grant ListT32 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