Iron Deficiency in Young Rats Alters the Distribution of Vitamin A between Plasma and Liver and between Hepatic Retinol and Retinyl Esters

Rosales, Francisco J.; Jang, Jing Tsz; Piñero, Domingo J.; Erikson, Keith M.; Beard, John L.; Ross, A. Catharine

doi:10.1093/jn/129.6.1223

Cited by 54 publications

(26 citation statements)

References 21 publications

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“…These authors also demonstrated decreased plasma RBP concentration in irondeficient rats (31). Iron deficiency lowers serum retinol, and vitamin A accumulates in the liver as retinyl esters, probably due to impaired activity of hepatic acid retinyl ester hydrolase, an iron-dependent enzyme (31). Consistent with the data from these animal studies, long-term supplementation with iron caused large increases in serum retinol in children (20).…”

Section: Rbp4 Insulin Resistance and Iron Overloadmentioning

confidence: 56%

“…An interaction between iron and vitamin A intake has also been well recognized in the past (15-17). Rosales et al (31) showed that the distribution of retinol through various body compartments is dependent on iron status, with higher concentrations of vitamin A in the livers of food-restricted control rats than in those of iron-deficient rats. These authors also demonstrated decreased plasma RBP concentration in irondeficient rats (31).…”

Section: Rbp4 Insulin Resistance and Iron Overloadmentioning

confidence: 99%

“…Rosales et al (31) showed that the distribution of retinol through various body compartments is dependent on iron status, with higher concentrations of vitamin A in the livers of food-restricted control rats than in those of iron-deficient rats. These authors also demonstrated decreased plasma RBP concentration in irondeficient rats (31). Iron deficiency lowers serum retinol, and vitamin A accumulates in the liver as retinyl esters, probably due to impaired activity of hepatic acid retinyl ester hydrolase, an iron-dependent enzyme (31).…”

Section: Rbp4 Insulin Resistance and Iron Overloadmentioning

confidence: 99%

“…It has been suggested that low plasma retinol concentrations were in fact caused by iron deficiency rather than vitamin A deficiency (20). Deficiency and supplementation of iron have different effects on the complicated intrahepatic balance between cellular uptake and mobilization of vitamin A and, hence, RBP4 (31)(32)(33).…”

Section: Rbp4 Insulin Resistance and Iron Overloadmentioning

confidence: 99%

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Circulating Retinol-Binding Protein-4 Concentration Might Reflect Insulin Resistance–Associated Iron Overload

2008

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OBJECTIVES-The mechanisms behind the association between retinol-binding protein-4 (RBP4) and insulin resistance are not well understood. An interaction between iron and vitamin A status, of which RBP4 is a surrogate, has long been recognized. We hypothesized that iron-associated insulin resistance could be behind the impaired insulin action caused by RBP4.RESEARCH DESIGN AND METHODS-Serum ferritin and RBP4 concentration and insulin resistance were evaluated in a sample of middle-aged men (n ϭ 132) and in a replication independent study. Serum RBP4 was also studied before and after iron depletion in patients with type 2 diabetes. Finally, the effect of iron on RBP4 release was evaluated in vitro in adipose tissue. RESULTS-A positive correlation between circulating RBP4and log serum ferritin (r ϭ 0.35 and r ϭ 0.61, respectively; P Ͻ 0.0001) was observed in both independent studies. Serum RBP4 concentration was higher in men than women in parallel to increased ferritin levels. On multiple regression analyses to predict serum RBP4, log serum ferritin contributed significantly to RBP4 variance after controlling for BMI, age, and homeostasis model assessment value. Serum RBP4 concentration decreased after iron depletion in type 2 diabetic patients (percent mean difference Ϫ13.7 [95% CI Ϫ25.4 to Ϫ2.04]; P ϭ 0.024). The iron donor lactoferrin led to increased dose-dependent adipose tissue release of RBP4 (2.4-fold, P ϭ 0.005) and increased RBP4 expression, while apotransferrin and deferoxamine led to decreased RBP4 release. CONCLUSIONS-The relationship between circulating RBP4and iron stores, both cross-sectional and after iron depletion, and in vitro findings suggest that iron could play a role in the RBP4 -insulin resistance relationship. Diabetes 57: [1918][1919][1920][1921][1922][1923][1924][1925] 2008 A dipose tissue is increasingly viewed as an endocrine organ that secretes many types of adipokines (such as leptin, tumor necrosis factor-␣, interleukin 6, and adiponectin) that modulate the action of insulin in other tissues. Retinol-binding protein-4 (RBP4), a new fat-derived adipokine that specifically binds to retinol, has recently been reported to provide a link between obesity and insulin resistance (1,2). Circulating RBP4 levels and adipose tissue RBP4 expression were raised in several different mouse models of obesity and insulin resistance. In these animal models, increasing the circulating levels of RBP4 leads to glucose intolerance, augmented hepatic gluconeogenesis, and attenuated insulin signaling in skeletal muscle, whereas knock-out of the RBP4 gene increases insulin sensitivity.In humans, different authors have reported increased serum RBP4 concentration in subjects with obesity, insulin resistance, or type 2 diabetes compared with lean subjects (2-6), although not all studies are concordant. At least two recent studies (7,8) did not observe a relationship between RBP4 and insulin resistance in women. Although some problems exist with serum RBP4 measurements (9), RBP4 mRNA was in fact downregulat...

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Section: Rbp4 Insulin Resistance and Iron Overloadmentioning

confidence: 56%

Section: Rbp4 Insulin Resistance and Iron Overloadmentioning

confidence: 99%

Section: Rbp4 Insulin Resistance and Iron Overloadmentioning

confidence: 99%

Section: Rbp4 Insulin Resistance and Iron Overloadmentioning

confidence: 99%

See 2 more Smart Citations

Circulating Retinol-Binding Protein-4 Concentration Might Reflect Insulin Resistance–Associated Iron Overload

2008

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“…In non-anaemic subjects, a test meal containing 1 000 µg retinol did not enhance iron absorption (Walczyk et al, 2003). Iron deficiency was shown to alter the distribution of retinol and retinyl esters between plasma and liver and to reduce plasma retinol concentrations in rats, despite adequate vitamin A intake and hepatic retinol stores (Amine et al, 1970;Staab et al, 1984;Rosales et al, 1999).…”

Section: 37mentioning

confidence: 99%

Scientific Opinion on Dietary Reference Values for vitamin A

Products¹

2015

EFSA Journal

126

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Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies derived Dietary Reference Values for vitamin A. The Panel considered that a concentration of 20 µg retinol/g liver can be used as a target for establishing the Average Requirement (AR) for vitamin A. In the absence of a better characterisation of the relationship between vitamin A intake and liver stores, a factorial approach was applied. This approach considered a total body/liver retinol store ratio of 1.25, a liver/body weight ratio of 2.4 %, a fractional catabolic rate of body retinol of 0.7 % per day, an efficiency of storage in the whole body for ingested retinol of 50 % and reference weights for women and men in the EU of 58.5 and 68.1 kg, respectively. ARs of 570 µg retinol equivalent (RE)/day for men and 490 µg RE/day for women were derived. Assuming a coefficient of variation (CV) of 15 %, Population Reference Intakes (PRIs) of 750 µg RE/day for men and 650 µg RE/day for women were set. For infants aged 7-11 months and children, the same equation as for adults was applied by using specific values for reference weight and liver/body weight ratio. For catabolic rate, the adult value corrected on the basis of a growth factor was used. ARs range from 190 µg RE/day in infants aged 7-11 months to 580 µg RE/day in boys aged 15-17 years. PRIs for infants and children were estimated using a CV of 15 % and range from 250 to 750 µg RE/day. For pregnancy and lactation, additional vitamin A requirements related to the accumulation of retinol in fetal and maternal tissues and transfer of retinol into breast milk were considered and PRIs of 700 and 1 300 µg RE/day, respectively, were set. Vitamin A is involved in vision as retinal, which plays a central role in the mechanisms of phototransduction, and in the systemic maintenance of the growth and integrity of cells in body tissues through the action of retinoic acid, which acts as regulator of genomic expression. The most specific clinical consequence of vitamin A deficiency is xerophthalmia, which encompasses a clinical spectrum of ocular manifestations. In low-income countries, vitamin A deficiency in young infants and children has been associated with increased infectious morbidity and mortality, including respiratory infection and diarrhoea. © EuropeanPreformed vitamin A is efficiently absorbed (70-90 %). The absorption of β-carotene appears to be highly variable (5-65 %), depending on food-and diet-related factors, genetic characteristics and the health status of the subject. The intestine is the primary tissue where dietary provitamin A carotenoids are converted to retinol. Retinol, in the form of retinyl esters, and provitamin A carotenoids enter the body as a component of nascent chylomicrons secreted into the lymphatic system. Most dietary retinol (in chylomicrons and chylomicron remnants) is taken up by the liver, which is the major site of retinol metabolism and storage. Hepatic retinyl esters are hydrolysed to free retinol, and delivered to ti...

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