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.

All Trans Retinoic Acid, Transforming Growth Factor β and Prostaglandin E2 in Mouse Plasma Synergize with Basophil-Secreted Interleukin-4 to M2 Polarize Murine Macrophages

“…Since the lipid soluble prostaglandin, PGE 2 , has been reported to be involved in M2 skewing [32,33] we then tested it with and without TGFβ. As shown in Fig 4D, TGFβ plus PGE 2 acted synergistically to enhance M2 skewing but even at levels substantially higher than that observed physiologically [34,35], they were far less potent than 5% MP at M2 skewing.…”

“…We then tested the combination of ATRA, TGFβ and PGE 2 , at levels reported to be present in MP [34,35] for their ability to M2 skew and found that, together, they elicited Arg1 levels similar to that of 5% MP (Fig 4F). Also, the ability of the combination of ATRA, TGFβ and PGE 2 to M2 skew was markedly inhibited by the inhibitors, NAC, U0126 and LY294002 (Fig 4F), mimicking the response of MP to these agents.…”

Inhibitory Effects of Retinol Are Greater than Retinoic Acid on the Growth and Adhesion of Human Refractory Cancer Cells

“…10,11) Rol significantly reduces cancer cell growth when given within a 1-20 µM concentration range (Fig. 1).…”

Dietary vitamin A regulates wingless-related MMTV integration site signaling to alter the hair cycle

“…50 But most mice consume these high levels on a regular basis; because most standard unpurified diets contain extra vitamin A. Dr. Napoli calls the amount of vitamin A in unpurified diets “Copious”; and his group recently showed that these diets are causing lasting effects that impede vitamin A research. 51 According to the National Health and Nutrition Examination Survey (NHANES), most Americans consume the recommended level of dietary vitamin A through diet alone. But a significant number of Americans receive 2–7 times the recommended level of vitamin A through supplements.…”