Effects of diet and strain on mouse serum and tissue retinoid concentrations

Abstract

The relationship between dietary vitamin A and all-trans-retinoic acid levels in serum and tissues had not been quantified. We determined the impact of dietary vitamin A on retinoid levels in serum, liver, kidney, testis, and epididymal white adipose of five mouse strains: AKR/J; BALB/cByJ; C3H/HeJ; C57BL/6J; 129S1/SvImJ. Retinoids were quantified in mice fed copious vitamin A (lab chow, ≥20 IU/g) followed by one month feeding a vitamin A-sufficient diet (4 IU/g), or after three generations of feeding a vitamin A-sufficient diet. Retinol and retinyl esters were measured by high-performance liquid chromatography with ultraviolet absorbance detection. All-trans-retinoic acid was quantified by liquid chromatography tandem mass spectrometry. The amounts of dietary vitamin A had long-term strain-specific effects on tissue retinyl ester, retinol and all-trans-retinoic acid concentrations. Three generations of feeding a vitamin A-sufficient diet decreased all-trans-retinoic acid in most tissues of most strains, in some cases more than 60%, compared to a diet with copious vitamin A. With both diets, all-trans-retinoic acid concentrations maintained an order of liver ≈ testis > kidney > white adipose tissue ≈ serum. Neither retinol nor all-trans-retinoic acid in serum reflected all-trans-retinoic acid concentrations in tissues. Strain and tissue-specific differences in retinol and all-trans-retinoic acid altered by different amounts of dietary vitamin A could have profound effects on retinoid action. This would be the case especially with the increased all-trans-retinoic acid values associated with the amounts of vitamin A and its precursors (carotenoids) in chow diets.

Figure 1. Retinoids in serum and tissues of five mouse strains.

Retinyl esters (RE), retinol and all-trans-retinoic acid (atRA) in serum and tissues. Mice were fed a VAS after weaning from dams fed a chow diet (generation 1). Generation 1 mice were maintained and bred on the VAS, continuing into the third generation. Retinoids were quantified in male mice after week 9 of the first generation (open bars), or week 10 of the third generation (filled bars). Tissues and serum of 3 to 10 mice were assayed for each strain and generation: eWAT, epididymal white adipose tissue. Data are means ± SE: *P<0.05; **P<0.005, ***P<0.001 relative to first generation values.

Figure 2. Relationships between retinol and atRA.

Retinol (x-axis) and atRA (y-axis) values for serum and tissues from first generation (left column) and third generation (right column) fed a VAS (eWAT, epididymal white adipose tissue): □, C3H; Δ, AKR; ▪, 129; •, C57; ◯, BALB. Linear regression analysis for each tissue and generation verified that none of the slopes differed significantly from zero.