Roles of vitamin A status and retinoids in glucose and fatty acid metabolism

2012 ◽  
Vol 90 (2) ◽  
pp. 142-152 ◽  
Author(s):  
Shi Zhao ◽  
Rui Li ◽  
Yang Li ◽  
Wei Chen ◽  
Yan Zhang ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Vitamin A ◽  
Metabolic Diseases ◽  
Retinoic Acid Receptor ◽  
Regulatory Element ◽  
Health Concern ◽  
Future Research ◽  
Lipogenic Genes ◽  
Glucose And Lipid Metabolism ◽  
Obesity And Diabetes

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 muscle. It proposes a mechanism by which the dietary and hormonal signals converge on the promoter of sterol regulatory element-binding protein 1c gene to induce its expression, and in turn, the expression of lipogenic genes in hepatocytes. Future research projects relevant to the VA’s roles in metabolic diseases are also discussed.

scholarly journals The Interactions of Insulin and Vitamin A Signaling Systems for the Regulation of Hepatic Glucose and Lipid Metabolism

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2160
Author(s):  
Guoxun Chen
Keyword(s):  
Retinoic Acid ◽  
Lipid Metabolism ◽  
Vitamin A ◽  
Future Research ◽  
Signaling Systems ◽  
Hormone Interactions ◽  
Glucose And Lipid Metabolism ◽  
Research Perspectives ◽  
Hepatic Glucose ◽  
X Receptors

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 signaling systems; the effects of VA status and activation of RARs and RXRs on metabolism and RAR and RXR phosphorylation; and possible interactions of insulin and RA in the regulation of hepatic genes for glucose and lipid metabolism. In addition, some future research perspectives for understanding of nutrient and hormone interactions are provided.

scholarly journals Unraveling the physiological roles of retinoic acid receptor-related orphan receptor α

2021 ◽  
Author(s):  
Ji Min Lee ◽  
Hyunkyung Kim ◽  
Sung Hee Baek
Keyword(s):  
Retinoic Acid ◽  
Molecular Mechanisms ◽  
Cancer Metabolism ◽  
Metabolic Diseases ◽  
Retinoic Acid Receptor ◽  
Critical Role ◽  
Orphan Receptor ◽  
Orphan Nuclear Receptor ◽  
Functional Link ◽  
Acid Receptor

AbstractRetinoic acid receptor-related orphan receptor-α (RORα) is a member of the orphan nuclear receptor family and functions as a transcriptional activator in response to circadian changes. Circadian rhythms are complex cellular mechanisms regulating diverse metabolic, inflammatory, and tumorigenic gene expression pathways that govern cyclic cellular physiology. Disruption of circadian regulators, including RORα, plays a critical role in tumorigenesis and facilitates the development of inflammatory hallmarks. Although RORα contributes to overall fitness among anticancer, anti-inflammatory, lipid homeostasis, and circadian clock mechanisms, the molecular mechanisms underlying the mode of transcriptional regulation by RORα remain unclear. Nonetheless, RORα has important implications for pharmacological prevention of cancer, inflammation, and metabolic diseases, and understanding context-dependent RORα regulation will provide an innovative approach for unraveling the functional link between cancer metabolism and rhythm changes.

scholarly journals Effects of Vitamin-A Status on Hamster Tracheal Epithellum in Viva in Vitro

1989 ◽  
Vol 11 (3) ◽  
pp. 1-6 ◽  
Author(s):  
Luigi M. De Luca ◽  
Elizabeth M. McDowell
Keyword(s):  
Retinoic Acid ◽  
Vitamin A ◽  
Retinoic Acid Receptor ◽  
Normal Liver ◽  
Acid Receptor ◽  
New Horizons ◽  
Vitamin A Status ◽  
Essential Nutrient ◽  
Hepatoma Tissue

In this paper we have suggested the new concept of exotrophic cells, i.e. cells that have conditionally escaped the need for an essential nutrient, such as vitamin A. These exotrophs might become fixed by a mutation and eventually contribute to the tumorigenic phenotype. The discovery of the retinoic acid receptor (RAR) has opened up new horizons in the search for the mechanism of action of retinoic acid [17; 18]. It is intriguing that a second retinoic acid receptor, RARE, is abundantly expressed in hepatoma tissue and not in normal liver; Benbrook et al. [191 suggest that the erroneous expression of the RARE might contribute to tumour development in liver. How and whether these findings relate to the vitamin-A-deficient status of hepatoma cells remains to be understood.

scholarly journals Retinoic Acid Reduces Glucocorticoid Sensitivity in C2C12 Myotubes by Decreasing 11β-Hydroxysteroid Dehydrogenase Type 1 and Glucocorticoid Receptor Activities

Endocrinology ◽  
2009 ◽  
Vol 150 (6) ◽  
pp. 2700-2708 ◽  
Author(s):  
Evelyne M. Aubry ◽  
Alex Odermatt
Keyword(s):  
Retinoic Acid ◽  
Vitamin A ◽  
Glucose Tolerance ◽  
Glucocorticoid Receptor ◽  
Hormonal Regulation ◽  
Skeletal Muscles ◽  
Metabolic Diseases ◽  
Hydroxysteroid Dehydrogenase ◽  
C2c12 Myotubes

Vitamin A is a nutrient with remarkable effects on adipose tissue and skeletal muscles, and plays a role in controlling energy balance. Retinoic acid (RA), the carboxylic form of vitamin A, has been associated with improved glucose tolerance and insulin sensitivity. In contrast, elevated glucocorticoids have been implicated in the development of insulin resistance and impaired glucose tolerance. Here, we investigated whether RA might counteract glucocorticoid effects in skeletal muscle cells by lowering 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1)-dependent local glucocorticoid activation and/or activation of glucocorticoid receptor (GR). We found a dose-dependent down-regulation of 11β-HSD1 mRNA expression and activity upon incubation of fully differentiated mouse C2C12 myotubes with RA. In addition, RA inhibited GR transactivation by an 11β-HSD1-independent mechanism. The presence of RA during myogenesis did not prevent myotube formation but resulted in relatively glucocorticoid-resistant myotubes, exhibiting very low 11β-HSD1 expression and GR activity. The use of selective retinoic acid receptor (RAR) and retinoid X receptor ligands provided evidence that these effects were mediated through RARγ. Importantly, short hairpin RNA against RARγ abolished the effect of RA on 11β-HSD1 and GR. In conclusion, we provide evidence for an important role of RA in the control of glucocorticoid activity during myogenesis and in myotubes. Disturbances of the nutrient and hormonal regulation of glucocorticoid action in skeletal muscles might be relevant for metabolic diseases.

scholarly journals Effect of retinoid status on α, β and γ retinoic acid receptor mRNA levels in various rat tissues

1992 ◽  
Vol 286 (3) ◽  
pp. 755-760 ◽  
Author(s):  
S Kato ◽  
H Mano ◽  
T Kumazawa ◽  
Y Yoshizawa ◽  
R Kojima ◽  
...  
Keyword(s):  
Gene Expression ◽  
Vitamin D ◽  
Retinoic Acid ◽  
Thyroid Hormone ◽  
Vitamin A ◽  
Retinoic Acid Receptor ◽  
Rat Tissues ◽  
Mrna Levels ◽  
Acid Receptor ◽  
Beta Gene

We have investigated the effects of retinoids, vitamin D and thyroid hormone on the levels of retinoic acid receptor (RAR)alpha, RAR beta and RAR gamma mRNAs in intact animals. Although vitamin A deficiency caused no significant changes in the levels of RAR alpha and RAR gamma mRNAs, the level of RAR beta transcripts was greatly decreased in various tissues of vitamin A-deficient rats, but was restored rapidly to a normal level after administration of retinoic acid. Retinol also restored the RAR beta mRNA level, but the magnitude and kinetics of the induction differed from those by retinoic acid. The use of specific inhibitors demonstrated that this autoregulation of RAR beta gene expression in vivo occurred at the transcriptional level. In addition, from these results it was postulated that the maintenance of the normal RAR beta mRNA levels seemed to require a threshold serum retinol concentration (about 25 micrograms/dl). Moreover, we found that administration of retinol and retinoic acid to normal rats caused the overexpression of RAR beta transcripts (2-15-fold) when compared with the control levels of RAR beta mRNA, although the levels of RAR alpha and RAR gamma mRNAs were not affected. Vitamin D and thyroid hormone did not modulate the levels of RAR transcripts. These findings clearly indicate the specific ligand regulation of RAR beta gene expression in intact animals. The altered levels of RAR beta according to retinoid status may affect retinoid-inducible gene expression.

Function of the retinoic acid receptors (RARs) during development (I). Craniofacial and skeletal abnormalities in RAR double mutants

Development ◽  
1994 ◽  
Vol 120 (10) ◽  
pp. 2723-2748 ◽  
Author(s):  
D. Lohnes ◽  
M. Mark ◽  
C. Mendelsohn ◽  
P. Dolle ◽  
A. Dierich ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Vitamin A ◽  
Congenital Malformations ◽  
Double Mutant ◽  
Congenital Abnormalities ◽  
Retinoic Acid Receptor ◽  
Retinoic Acid Receptors ◽  
Acid Receptor ◽  
Null Mutants

Numerous congenital malformations have been observed in fetuses of vitamin A-deficient (VAD) dams [Wilson, J. G., Roth, C. B., Warkany, J., (1953), Am. J. Anat. 92, 189–217]. Previous studies of retinoic acid receptor (RAR) mutant mice have not revealed any of these malformations [Li, E., Sucov, H. M., Lee, K.-F., Evans, R. M., Jaenisch, R. (1993) Proc. Natl. Acad. Sci. USA 90, 1590–1594; Lohnes, D., Kastner, P., Dierich, A., Mark, M., LeMeur, M., Chambon, P. (1993) Cell 73, 643–658; Lufkin, T., Lohnes, D., Mark, M., Dierich, A., Gorry, P., Gaub, M. P., Lemeur, M., Chambon, P. (1993) Proc. Natl. Acad. Sci. USA 90, 7225–7229; Mendelsohn, C., Mark, M., Dolle, P., Dierich, A., Gaub, M.P., Krust, A., Lampron, C., Chambon, P. (1994a) Dev. Biol. in press], suggesting either that there is a considerable functional redundancy among members of the RAR family during ontogenesis or that the RARs are not essential transducers of the retinoid signal in vivo. In order to discriminate between these possibilities, we have generated a series of RAR compound null mutants. These RAR double mutants invariably died either in utero or shortly after birth and presented a number of congenital abnormalities, which are reported in this and in the accompanying study. We describe here multiple eye abnormalities which are found in various RAR double mutant fetuses and are similar to those previously seen in VAD fetuses. Interestingly, we found further abnormalities not previously reported in VAD fetuses.(ABSTRACT TRUNCATED AT 250 WORDS)

Retinoic acid is required in the mouse embryo for left-right asymmetry determination and heart morphogenesis

Development ◽  
1999 ◽  
Vol 126 (12) ◽  
pp. 2589-2596 ◽  
Author(s):  
C. Chazaud ◽  
P. Chambon ◽  
P. Dolle
Keyword(s):  
Retinoic Acid ◽  
Vitamin A ◽  
Mouse Embryo ◽  
Time Course ◽  
Retinoic Acid Receptor ◽  
Mouse Embryos ◽  
Anteroposterior Patterning ◽  
Heart Looping ◽  
Left Right Asymmetry

Determination of the left-right position (situs) of visceral organs involves lefty, nodal and Pitx2 genes that are specifically expressed on the left side of the embryo. We demonstrate that the expression of these genes is prevented by the addition of a retinoic acid receptor pan-antagonist to cultured headfold stage mouse embryos, whereas addition of excess retinoic acid leads to their symmetrical expression. Interestingly, both treatments lead to randomization of heart looping and to defects in heart anteroposterior patterning. A time course analysis indicates that only the newly formed mesoderm at the headfold-presomite stage is competent for these retinoid effects. We conclude that retinoic acid, the active derivative of vitamin A, is essential for heart situs determination and morphogenesis.

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