The hepatic retinyl ester hydrolase activity is depressed at the onset of diabetes in BB rats (original) (raw)
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Role of vitamin A degradation in the control of hepatic levels in the rat
The Journal of nutrition, 1989
The relationship between excess vitamin A intake and accumulation in various tissues, including the liver, was studied in rats fed for 45 d four levels of vitamin A: 1, 6, 30 and 100 IU/kcal. As vitamin A intake increased, progressively smaller fractions of the administered vitamin A were recovered in tissue. The decrease in fractional recovery in the tissues examined was calculated from the differences between intake, tissue level and excretion, and was found to increase after administration of high vitamin A diets. This could be explained, at least in part, on the basis of an enhanced rate of vitamin A degradation as a function of the increased concentration of retinol in the liver. At high tissue retinol concentrations, calculated rates of retinol metabolism via the hepatic cytosolic retinol dehydrogenase (EC 1.1.1.1) and the recently discovered microsomal retinol dehydrogenase and oxidase vastly exceeded the decrease in fractional recovery of vitamin A accumulation in the tissue...
Effects of retinoic acid on the metabolism of vitamin a in rat liver
Nutrition Research, 1986
Sprague-Dawley male rats with adequate storage of vitamin A were fed vitamin A deficient diet either alone (RA-)~ or supplemented with retinolc acid (RA+). The rats were sacrificed at different days for the measurement of free retlnol and the composition of retinyl esters in liver. At the same time the plasma retinol levels of these rats were also determined. Supplementation of retinoic acid significantly lowered the plasma retlnol levels with a concomitant slower depletion of the total vitamin A in the liver of RA § rats as compared.to RArats. The ratio of retlnyl esters to free retinol in the liver tissue of RA-rats decreased with time, whereas in RA+ rat livers the ratio remained constant. The percentage distribution of retinyl esters in the liver tissue revealed a significant decrease in saturated retlnyl esters with an increase in unsaturated retinyl esters in the RA+ group compared to RA-group. These data support the earlier findings that retinoic acid spares the utilization of retinol and suggest that it may affect the release of retinol from retinyl esters in the liver.
Regulation of Hepatic Retinol Metabolism: Perspectives from Studies on Vitamin A Status
The Journal of Nutrition, 2004
Liver vitamin A (retinol) is obtained from several sources and is subject to multiple fates. Lecithin: retinol acyltransferase (LRAT), a microsomal enzyme present in liver and several other retinol-metabolizing tissues, esterifies retinol that is associated with a cellular retinol-binding protein, CRBP or CRBP-II. Recent research has shown that LRAT mRNA expression and enzyme activity are regulated in a tissue-specific manner. In vitamin A-deficient liver, both LRAT mRNA and activity are significantly down-regulated as well as rapidly induced after the administration of vitamin A or its principal hormonal metabolite, retinoic acid (RA). In long-term feeding studies and the metabolic steady state, liver LRAT is expressed dose-dependently across a wide range of dietary vitamin A. Additionally, an RA-inducible cytochrome P450, P450RAI or CYP26, is down-regulated in liver during vitamin A deficiency and up-regulated dose-dependently by dietary vitamin A and exogenous RA. Based on these results, we propose that LRAT and CYP26 serve as two molecular mechanisms, coordinately regulated by all-trans-RA, to control the availability of retinol and RA, respectively. The LRAT reaction, besides providing a readily retrievable storage form of vitamin A, may regulate the availability of retinol to other pathways, while the CYP26 reaction may serve to prevent a detrimental "overshoot" of RA concentration. Moreover, retinoid metabolism in the liver is likely to be closely integrated with that in peripheral tissues through the rapid interorgan transfer and recycling of retinoids, affecting the whole-body economy of vitamin A. J. Nutr. 134: 269S-275S, 2004.
Is There A Role of Vitamin A in Hepatic Glucose and Fatty Acid Metabolism?
Journal of Nutrition & Food Sciences, 2012
Vitamin A (VA, retinol) is an indispensible, lipid-derived micronutrient contributing to the general health of an individual. Retinoids are VA and its derived metabolites that have profound effects on a variety of physiological processes, such as embryogenesis and cellular differentiation [1]. More recently, retinoids have been proposed to play roles in energy homeostasis such as adaptive thermogenesis and adipogenesis [2]. The roles of retinoids in lipid and glucose metabolism have been indicated and potentially linked to the development of chronic metabolic diseases such as obesity and diabetes [3-7]. Obesity and comorbidities are the physiological consequences of a disruption in the regulation of body energy storage, which is associated with profound changes in hepatic glucose and lipid metabolism. These changes are often attributed to the expression levels of hepatic genes involved in glucose and lipid metabolism. The active metabolite of VA responsible for the regulation of gene expression is retinoic acid (RA), which exists in multiple isomeric forms. They activate two families of nuclear receptors: retinoic acid receptors (RARα, β, and γ; activated by all-trans and 9-cis RA) and retinoid X receptors (RXRα, β, and γ; activated by 9-cis RA). RAR/RXR hetero-and RXR/RXR homo-dimer bind to RA-responsive elements (RAREs) in the promoters of the RA responsive genes, and regulate their expression upon activation [1].
Roles of vitamin A status and retinoids in glucose and fatty acid metabolism
Biochemistry and Cell Biology, 2012
The rising prevalence of metabolic diseases, such as obesity and diabetes, has become a public health concern. Vitamin A (VA, retinol) is an essential micronutrient for a variety of physiological processes, such as tissue differentiation, immunity, and vision. However, its role in glucose and lipid metabolism has not been clearly defined. VA activities are mediated by the metabolite of retinol catabolism, retinoic acid, which activates the retinoic acid receptor and retinoid X receptor (RXR). Since RXR is an obligate heterodimeric partner for many nuclear receptors involved in metabolism, it is reasonable to assume that VA status and retinoids contribute to glucose and lipid homeostasis. To date, the impacts of VA and retinoids on energy metabolism in animals and humans have been demonstrated in some basic and clinical investigations. This review summarizes the effects of VA status and retinoid treatments on metabolism of the liver, adipocytes, pancreatic β-cells, and skeletal muscl...
Roles of Vitamin A Metabolism in the Development of Hepatic Insulin Resistance
ISRN Hepatology, 2013
The increase in the number of people with obesity- and noninsulin-dependent diabetes mellitus has become a major public health concern. Insulin resistance is a common feature closely associated with human obesity and diabetes. Insulin regulates metabolism, at least in part,viathe control of the expression of the hepatic genes involved in glucose and fatty acid metabolism. Insulin resistance is always associated with profound changes of the expression of hepatic genes for glucose and lipid metabolism. As an essential micronutrient, vitamin A (VA) is needed in a variety of physiological functions. The active metablite of VA, retinoic acid (RA), regulates the expression of genes through the activation of transcription factors bound to the RA-responsive elements in the promoters of RA-targeted genes. Recently, retinoids have been proposed to play roles in glucose and lipid metabolism and energy homeostasis. This paper summarizes the recent progresses in our understanding of VA metabolis...
Journal of Nutrition, 2007
The relation between vitamin A (VA) nutritional status and the metabolism of all-trans-retinoic acid (RA) is not well understood. In this study, we determined the tissue distribution and metabolism of a test dose of [ 3 H]-RA in rats with graded, diet-dependent, differences in VA status. The design included 3 groups, designated VA-deficient, VA-marginal, and VA-adequate, with liver total retinol concentrations of 9.7, 35.7 and 359 nmol/g, respectively, (P , 0.05), and an additional group of VA-deficient rats treated with a single oral dose of retinyl palmitate (RP) 20 h before the injection of [ 3 H]-RA. Plasma, liver, lung, and small intestines, collected 30 min after [ 3 H]-RA, were analyzed for total 3 H, unmetabolized [ 3 H]-RA, polar organic-phase metabolites of [ 3 H]-RA, and aqueous phase [ 3 H]-labeled metabolites. In all groups, [ 3 H]-RA was rapidly removed from plasma and concentrated in the liver. VA deficiency did not prevent the oxidative metabolism of RA. Nevertheless, the quantity of [ 3 H]-RA metabolites in plasma and the ratio of total [ 3 H]-polar metabolites to unmetabolized [ 3 H]-RA in liver varied directly with VA status (VA-adequate. VA-marginal. VA-deficient, P , 0.05). Moreover, supplementation of VA-deficient rats with RP reduced the metabolism of [ 3 H]-RA, similar to that in VA-adequate or VAmarginal rats. Liver retinol concentration, considered a proxy for VA status, was correlated (P , 0.05) with [ 3 H]-RA metabolites in liver (R 2 ¼ 0.54), plasma (R 2 ¼ 0.44), lung (R 2 ¼ 0.40), intestine (R 2 ¼ 0.62), and all combined (R 2 ¼ 0.655). Overall, the results demonstrate close linkage between dietary VA intake, hepatic storage of VA, and the degradation of RA and suggest that measuring plasma retinoid metabolites after a dose of RA may provide insight into the metabolism of this bioactive retinoid by visceral organs.
Cells
The pandemics of obesity and type 2 diabetes have become a concern of public health. Nutrition plays a key role in these concerns. Insulin as an anabolic hormonal was discovered exactly 100 years ago due to its activity in controlling blood glucose level. Vitamin A (VA), a lipophilic micronutrient, has been shown to regulate glucose and fat metabolism. VA’s physiological roles are mainly mediated by its metabolite, retinoic acid (RA), which activates retinoic acid receptors (RARs) and retinoid X receptors (RXRs), which are two transcription factors. The VA status and activations of RARs and RXRs by RA and synthetic agonists have shown to affect the glucose and lipid metabolism in animal models. Both insulin and RA signaling systems regulate the expression levels of genes involved in the regulation of hepatic glucose and lipid metabolism. Interactions of insulin and RA signaling systems have been observed. This review is aimed at summarizing the history of diabetes, insulin and VA si...
Vitamin A Turnover in Rats as Influenced by Vitamin A Status1
2010
Vitamin A turnover was studied in rats fed vitamin A-sufficient (+A) or vitamin A-deficient (-A) diets for 24-25 days. Hepatic vitamin A stores of the +A group (543 /ig) were significantly larger than those of the -A group (11 pig)and similarly, the plasma vitamin A concentration of the + A group (56 ptg/dl) was significantly higher than that of the -A group (26 ¿tg/dl). Rats were injected intravenously with plasma containing tritium-labeled retinol (3H-ROH) obtained from vitamin A-deficient donor rats previously fed 3H-ROH. Plasma samples from injected recipients were collected over a 48-hour period. Kinetic analysis of plasma tracer concentration versus time curves indicated that the data fit a threepool model. The plasma vitamin A turnover rate of the +A group was significantly more rapid than that of the -A group ). Plasma fractional turnover rates for the +A group (1.31 hour"1) were not significantly different from those of the -A group (0.90 hour"1). The data suggest that for both dietary groups, the metabolism of retinol associated with the prealbumin and retinolbinding protein complex involved extensive recycling among the liver, plasma, interstitial fluid and peripheral tissues.
Changes on levels of B6 vitamin and aminotransferase in the liver of diabetic animals
Diabetes Research and Clinical Practice, 1990
We measured aminotransferase activity and vitamin B, content in the livers of diabetic mice. Two different types of mice were used for the measurements, spontaneously non-obese diabetic (NOD) or alloxan-induced diabetic (Allo) mice, and control mice were either non-diabetic NOD or Institute of Cancer Research (ICR). The liver of diabetic mice had more aspartate aminotransferase (AST) activity than those of normal mice. The diabetic livers also had more vitamin B, than did normal livers, and pyridoxamine (PM) levels were particularly high but pyridoxal (PL) levels were not. ICR livers showed hepatic alanine aminotransferase activities inversely correlated with blood glucose concentrations, while diabetic livers did not. The abundance of AST and B, in the diabetic liver is consistent with the great need for gluconeogenic substrate there. This is understandable in that most aminotransferases require B, vitamins, and especially the correlation between s-AST and PM levels was recognized in the diabetic liver. Conversely, the AST and PM levels were negatively correlated in normal mice. A metabolic shift towards gluconeogenesis apparently produces more B, and PM while it induced holo-AST synthesis. Kotake and Inada [5], Lepkovsky et al. [6] and Takatsuki 569, Japan. Beaton et al. [7] induced the diabetic state by 0168-8227/90/$03.50 0 1990 Elsevier Science Publishers B.V. (Biomedical Division)