Title

Effects of vitamin A deficiency on retinoid and energy metabolism in liver and white adipose tissue

Date of Completion

January 2008

Keywords

Biology, Molecular|Biology, Animal Physiology|Health Sciences, Nutrition

Degree

Ph.D.

Abstract

White adipose tissue (WAT) and liver play an important role in retinoid and energy metabolism. We studied certain effects of vitamin A status on white adipose tissue and liver on whole body metabolism by comparing mice fed a vitamin A sufficient (VAS) diet to mice fed a vitamin A deficient (VAD) diet. We report that vitamin A deficiency induced profound changes in the expression of genes involved in retinoid metabolism in the liver, resulting in a decrease in genes involved in retinol storage and retinoic acid (RA) synthesis in order to maintain plasma retinol levels.^ Furthermore, VAD induced a decrease in total body weight in part due to a decrease in white adipose tissue mass. This was not caused by an unregulated increase in lipolysis in WAT in order to mobilize retinoid stores. Instead, we found that preadipocytes were unable to differentiate into mature fat storing adipocytes under VAD conditions as seen by the decrease gene expression of several WAT differentiation markers such as Ppar-γ, C/ebp-α, lipin 1 and Srebp1. Broad alterations in lipid metabolism were found at the level of gene expression in VAD epWAT, including a decrease in the expression of genes encoding enzymes involved in lipogenesis and β-oxidation. In fasting mice, there was a decrease in plasma free fatty acids levels, likely due to decreased lipid efflux from WAT in VAD, leading to a decrease in triglycerides in liver and muscle. Undifferentiated WAT also affected plasma adipokines levels in that plasma leptin and adiponectin levels were decreased in VAD whereas TNF-α levels were increased. These changes could contribute to broader metabolic complications, particularly in decreased insulin sensitivity. ^ Finally, we studied the effects of VAD and decreased WAT mass in liver. Fed VAD mice had increased hepatic TG whereas fasted VAD mice had decreased hepatic TG levels. These variations in hepatic TG levels are associated with changes in the expression of genes involved hepatic lipid metabolism. Alterations in hepatic and WAT lipid metabolism were likely due in part to the decreased activation of the PPAR-RXR heterodimer, essential regulators of lipid metabolism in WAT and liver. ^