Lung retinyl ester is low in young adult rats fed a vitamin A deficient diet after weaning, despite neonatal vitamin A supplementation and maintenance of normal plasma retinol

Abstract

Although it is understood that plasma retinol concentration is not proportional to the concentration of vitamin A stored in liver, plasma retinol still is often used as an indicator of vitamin A status. An aim of vitamin A supplementation strategies is to maintain plasma retinol concentration in a range considered adequate, generally >1.05 micromol/L in humans, with some adjustment for age. In the present study in rats, we addressed the following question: Does lung vitamin A increase postnatally, as is observed in rats fed a vitamin A-adequate diet, if plasma retinol is maintained at approximately 1 micromol/L by supplementation at neonatal age, but the weaning diet is deficient in vitamin A? We treated rats on postnatal d 6, 7, and 8 with placebo (oil), vitamin A, retinoic acid (RA), and a nutrient-metabolite combination of vitamin A and RA, VARA, after which tissues were analyzed on d 9. Other rats treated identically as neonates were fed a vitamin A-deficient diet from 3-9 wk of age, and in parallel, another group of rats was fed a vitamin A-adequate diet. Although supplementation with vitamin A or VARA elevated liver and lung retinyl esters (RE) on d 9 (P < 0.0001), and prevented the fall in plasma retinol to <1 micromol/L by 9 wk of age, when the diet was vitamin A-deficient, lung RE fell to 28% of the concentration present in the lungs of rats fed the vitamin A-adequate diet (P < 0.0001). We infer that the lungs depend, at least in part, on the uptake of dietary vitamin A, probably from chylomicrons, to develop RE stores in the postweaning growth period.

FIGURE 1

Design of study (A) and liver total retinol at 9 d and 9 wk of age (B) in rats treated as neonates with oil, vitamin A (VA), RA, or VARA. The box showing 70 nmol/g (20 µg/g) represents a value considered to indicate sufficient liver retinol storage in adult humans (see text). Values are means ± SE, n = 4 (9 d) and 6 (9 wk). Means without a common letter differ, P < 0.0001. The reference group of 9-wk-old VA–adequate rats marked b′ did not differ from the 9-wk groups marked b, but was not compared with the 9-d-old rats.

FIGURE 2

Plasma retinol at 9 d and 9 wk of age in rats treated as neonates with oil, vitamin A (VA), RA, or VARA. At 9 wk the value for a group of same-aged rats fed the vitamin A–adequate diet is also shown. The box shows values that have been used as indicators of vitamin A status in humans (see text). Values are means ± SE, n = 4 (9 d) and 6 (9 wk). Means without a common letter differ, P < 0.05. The reference group of 9-wk-old VA–adequate rats marked b′ did not differ from the 9-wk groups marked b, but was not compared with the 9-d-old rats.

FIGURE 3

Lung total retinol at 9 d and 9 wk of age in rats treated as neonates with oil, vitamin A (VA), RA, or VARA. At 9 wk the value for a group of same-aged rats fed vitamin A–adequate diet is also shown. No reference values are shown, as none have been established for lung. Values are means ± SE, n = 4 (9 d) and 6 (9 wk). Means without a common letter differ, P < 0.0001. The reference group of 9-wk-old VA–adequate rats marked * differed from the other 9-wk groups (P < 0.001), but was not compared with the 9-d-old rats.

FIGURE 4

Model of situations and outcomes resulting from neonatal supplementation with vitamin A or VARA, and a postweaning diet either lacking or adequate in vitamin A. (A) Supplementation with vitamin A or VARA would be expected to increase lung total retinol in the neonatal period, resulting in somewhat higher levels in the lungs at 9 wk, as compared with supplementation with oil or RA alone (see Fig. 3), but not to the level observed in rats fed vitamin A after weaning. (B) Regardless of neonatal vitamin A supplementation (dashed line without vitamin A or VARA; upper solid line with these treatments), the daily input of dietary vitamin A, mostly as RE, supports the gradual accumulation of vitamin A in the lungs, leading to the adult level.