The Roles of Vitamin A in the Regulation of Carbohydrate, Lipid, and Protein Metabolism

Chen, Wei; Chen, Guoxun

doi:10.3390/jcm3020453

Cited by 69 publications

(53 citation statements)

References 185 publications

(219 reference statements)

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“…Mild symptoms of hypovitaminosis manifested in the form of slight periocular inflammation and weak vocalizations in a few animals shortly before hibernation, but the majority showed no signs of hypovitaminosis A. Liver retinol levels were undetectable in VAD2 animals throughout the study. Interestingly, liver retinol stores in our VAC squirrels were high relative those in other laboratory rodents, although no signs of hypervitaminosis 11,40 were observed. Liver stores in squirrels not associated with the current study, some of which were euthanized immediately after trapping from the wild, were similarly high, suggesting that this condition is normal for this species.…”

Section: Discussioncontrasting

confidence: 49%

Developing a Model of Vitamin A Deficiency in a Hibernating Mammal, the 13-Lined Ground Squirrel (Ictidomys tridecemlineatus)

2018

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Retinoic acid, a bioactive metabolite of vitamin A, plays key roles in immune function and vision and adipose tissue development. Our goal was to study the effect of vitamin A deficiency in physiologic changes seen in hibernating 13-lined ground squirrels (Ictidomys tridecemlineatus). In this study, we first developed a model of vitamin A deficiency that was based on published mouse models; we then examined the role of RA in the circannual cycle of and adipose accumulation in this hibernating species. Gravid female ground squirrels began consuming a deficient diet during the last 2 wk of their 4-wk gestation; pups received the diet until they were 8 wk old, when severe symptoms of hypovitaminosis were observed, requiring the animals' removal from the protocol. Body size and adipose mass were significantly lower in vitamin-deficient pups than controls. To avoid these complications, we developed a second model, in which pups started on the deficient diet after weaning. The revised model produced few symptoms of deficiency, and squirrels were able to remain on the diet through spring emergence. Liver retinol analysis showed that deficient squirrels essentially had no vitamin A stores. Our data suggest that 13-lined ground squirrels maintain higher concentrations of stored retinol than other rodent species, such that their dietary needs may differ from those of traditional laboratory rodent models. Our results indicate that ground squirrels are especially susceptible to vitamin A deficiency, and ground squirrels should not be fed a deficient diet until after weaning, to avoid severe symptoms. Interestingly, vitamin A deficiency does not seem to affect this species' ability to hibernate successfully.

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Section: Discussioncontrasting

confidence: 49%

Developing a Model of Vitamin A Deficiency in a Hibernating Mammal, the 13-Lined Ground Squirrel (Ictidomys tridecemlineatus)

2018

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“…Retinal serves as the cofactor for the visual cycle, whereas atRA supports systemic effects of vitamin A by sustaining spermatogenesis, embryonic development, epithelial differentiation, and nervous and immune system functions (Ulbricht et al, 2012; Hogarth & Griswold, 2013). atRA also controls energy balance and adiposity and suppresses inflammation (Chen & Chen, 2014; Brown & Noelle, 2015). …”

Section: Introductionmentioning

confidence: 99%

Cellular retinoid binding-proteins, CRBP, CRABP, FABP5: Effects on retinoid metabolism, function and related diseases

Napoli

2017

Pharmacology & Therapeutics

195

180

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Cellular binding-proteins (BP), including CRBP1, CRBP2, CRABP1, CRABP2, and FABP5, shepherd the poorly aqueous soluble retinoids during uptake, metabolism and function. Holo-BP promote efficient use of retinol, a scarce but essential nutrient throughout evolution, by sheltering it and its major metabolite all-trans-retinoic acid from adventitious interactions with the cellular milieu, and by imposing specificity of delivery to enzymes, nuclear receptors and other partners. Apo-BP reflect cellular retinoid status and modify activities of retinoid metabolon enzymes, or exert non-canonical actions. High ligand binding affinities and the nature of ligand sequestration necessitate external factors to prompt retinoid release from holo-BP. One or more of cross-linking, kinetics, and colocalization have identified these factors as RDH, RALDH, CYP26, LRAT, RAR and PPARβ/δ. Michaelis-Menten and other kinetic approaches verify that BP channel retinoids to select enzymes and receptors by protein-protein interactions. Function of the BP and enzymes that constitute the retinoid metabolon depends in part on retinoid exchanges unique to specific pairings. The complexity of these exchanges configure retinol metabolism to meet the diverse functions of all-trans-retinoic acid and its ability to foster contrary outcomes in different cell types, such as inducing apoptosis, differentiation or proliferation. Altered BP expression affects retinoid function, for example, by impairing pancreas development resulting in abnormal glucose and energy metabolism, promoting predisposition to breast cancer, and fostering more severe outcomes in prostate cancer, ovarian adenocarcinoma, and glioblastoma. Yet, the extent of BP interactions with retinoid metabolon enzymes and their impact on retinoid physiology remains incompletely understood.

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“…Following dietary intake from foods of plant and/or animal origin, retinol is transported as retinyl esters with triacylglycerol-rich chylomicrons to the liver where it can either be stored in hepatic stellate cells or exported to peripheral tissue bound to retinol-binding protein 4 (RBP4) and transthyretin. Retinol is then converted to RA in target tissues where it functions as a ligand for nuclear RA receptors with several target genes involved in growth and differentiation, metabolism of macronutrients [2], and the immune system [3].…”

Section: Introductionmentioning

confidence: 99%

Creatinine, total cysteine and uric acid are associated with serum retinol in patients with cardiovascular disease

et al. 2019

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Purpose We hypothesized that biomarkers and dietary factors related to cardiovascular disease risk were associated with serum retinol and evaluated these potential associations in patients with suspected coronary artery disease (CAD). Methods We used cross-sectional data from 4116 patients hospitalised for suspected CAD. Dietary data were obtained from a subgroup of 1962 patients using a food frequency questionnaire. Potential biomarkers and dietary factors were explored using linear regression modelling adjusted for age and sex. Regression coefficients and corresponding confidence intervals (CI) are given as % change in serum retinol per unit change in the predictors. Analyses were performed in the total population and in strata of serum retinol tertiles. Results In age-and sex-adjusted models, serum creatinine (standardized β: 0.38, 95% CI [0.35, 0.42]), plasma total cysteine (0.26, [0.23, 0.29]), serum uric acid (0.30, [0.26, 0.33]) and plasma neopterin (0.22, [0.18, 0.25]) were positively associated, whereas plasma serine (− 0.15, [− 0.18, − 0.12]) and serum C-reactive protein (− 0.15, [− 0.18, − 0.12]) were inversely associated with serum retinol. When we included the significant biomarkers in a multivariate model, the model explained 33% of the variability (R 2 = 0.33) in serum retinol. The results were similar in the lower and upper tertiles of serum retinol. Weak or no associations were observed for dietary factors. Conclusions In patients with suspected CAD, concentrations of creatinine, cysteine and uric acid were positively associated with serum retinol. Future studies should assess whether retinol concentrations are influenced by metabolic alterations in patients at risk of cardiovascular disease.

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The Roles of Vitamin A in the Regulation of Carbohydrate, Lipid, and Protein Metabolism

Cited by 69 publications

References 185 publications

Developing a Model of Vitamin A Deficiency in a Hibernating Mammal, the 13-Lined Ground Squirrel (Ictidomys tridecemlineatus)

Developing a Model of Vitamin A Deficiency in a Hibernating Mammal, the 13-Lined Ground Squirrel (Ictidomys tridecemlineatus)

Cellular retinoid binding-proteins, CRBP, CRABP, FABP5: Effects on retinoid metabolism, function and related diseases

Creatinine, total cysteine and uric acid are associated with serum retinol in patients with cardiovascular disease

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