Vitamin A status affects the Body Mass Gain and Hepatic Gene Expression in Rats fed a High‐Fat Diet

Abstract

IntroductionVitamin A (VA) plays a role in variety of physiological functions from development to metabolic homeostasis. High‐fat (HF) diet has been shown to cause the development of metabolic diseases such as obesity and type II diabetes. We hypothesize that VA status may affect the gain of body mass in rats fed a HF diet and regulate the expression levels of genes involved in hepatic glucose and fatty acid metabolism.MethodsSprague Dawley (SD) rats at weaning were fed either a HF‐VA sufficient (HF‐VAS) or HF‐VA deficient (HF‐VAD) diet for 8 weeks. The HF‐VAS and HF‐VAD diets are isocaloric. Their body mass and food intake were recorded once a week. The expression levels of hepatic genes for glucose and fatty acid metabolism, and insulin signaling pathway were determined via immunoblotting.ResultsFrom week 6, body mass of HF‐VAD rats was significantly lower than that of VAS group. The total food intake was similar between VAD and VAS groups. The liver mass and white adipose mass of HF‐VAD group were also significant smaller than that of HF‐VAS group. The hepatic expression level of Cytochrome P450 26A1 protein in HF‐VAS group is higher than that in HF‐VAD group, suggesting reduced retinoic acid production. For glucose metabolism, the HF‐VAD rats had higher glycogen synthase 3α (GSK‐3α) and lower GSK‐3β expression levels than the HF‐VAS rats did. The expression levels of glucokinase and cytosolic form of phosphoenoylpyruvate carboxykinase in HF‐VAS group are higher than that in HF‐VAD group. Proteins levels of acetyl‐CoA carboxylase (ACC), phospho‐ACC, fatty acid synthase, and ATP citrate lyase in fatty acid synthesis, are similar between two groups. The levels of insulin receptor beta subunit and insulin receptor substrate 1 are increased in HF‐HF‐VAD rats, while that of insulin receptor substrate 2 are decreased. The expression level of mitogen‐activated protein kinase of HF‐VAD group was higher than that of HF‐VAS group.ConclusionsVA status reduces the body mass gain in rats fed a HF diet. In addition, the expression levels of genes for glucose metabolism and insulin signaling pathway are also altered by the development of VA deficiency in these rats. These results support our previous observations that VA status and its metabolism affect the hepatic expression levels of insulin‐regulated genes in rats fed the diets with normal fat content. More studies are needed to determine the underlying mechanisms for these changes.Support or Funding InformationInternal funding