1 How Dietary Deficiency Studies Have Illuminated the Many Roles …
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New methods for assessing vitamin A status need to be developed, validated, and
used to accurately define vitamin A deficiency for different animals, age groups,
cultures, and physiologic states. In addition, systems-based approaches and analyses
are needed to assess how vitamin A action in one tissue is influenced by processes
and actions occurring in neighboring or distant tissues that absorb, store, or release
vitamin A, or that secrete factors that synergize with vitamin A.
Have All Actions of Vitamin A Been Described?
Substantial evidence from re-feeding and targeted mutation experiments has given
rise to the canonical view that vitamin A indirectly promotes genomic responses
by serving as a precursor for retinoic acid-induced activation of nuclear receptor
complexes (Asson-Batres and Rochette-Egly 2014, 2016) However, current findings
strongly support the notion that vitamin A “…controls a larger spectrum of biological
activities than previously recognized” (Noy 2016). These actions include
(a) non-canonical, non-genomic, mechanisms of action of vitamin A via its
derivative, retinoic acid (Piskunov et al. 2014; Rochette-Egly 2015);
(b) effects of vitamin A, itself, in conjunction with retinol binding protein (RBP),
wherein holo-RBP binds to and activates the cytosolic membrane receptor, Stimulated by Retinoic Acid 6 (STRA6), which then activates the JAK-STAT pathway
and the transcription of genes beyond those that are activated by canonical retinoic
acid signaling (Noy 2016);
(c) the direct action of vitamin A on mitochondrial energetics and cytoplasmic
signaling (Hammerling 2016a, b); and
(d) the indirect effects of vitamin A on the epigenome through the actions of its
derivative, retinoic acid (Bar-El and Reifen 2017).
Future work is needed to elucidate these and other, as yet, unknown roles of
vitamin A and the consequences of deficiency.
References
Aberle SDB (1934) Neurological disturbances in rats reared on diets deficient in vitamin A. J Nutr
7:445–461
Asson-Batres MA, Rochette-Egly C (2014) The biochemistry of retinoic acid receptors I: structure,
activation, and function at the molecular level. Springer
Asson-Batres MA, Rochette-Egly C (2016) The biochemistry of retinoid signaling II: the physiology
of Vitamin A—Uptake, transport. Springer, Metabolism and Signaling
Asson-Batres MA, Smith WB (2006) Localization of retinaldehyde dehydrogenases and retinoid
binding proteins to sustentacular cells, glia, Bowman’s gland cells, and stroma: potential sites of
retinoic acid synthesis in the postnatal rat olfactory organ. J Comp Neurol 496:149–171
21
New methods for assessing vitamin A status need to be developed, validated, and
used to accurately define vitamin A deficiency for different animals, age groups,
cultures, and physiologic states. In addition, systems-based approaches and analyses
are needed to assess how vitamin A action in one tissue is influenced by processes
and actions occurring in neighboring or distant tissues that absorb, store, or release
vitamin A, or that secrete factors that synergize with vitamin A.
Have All Actions of Vitamin A Been Described?
Substantial evidence from re-feeding and targeted mutation experiments has given
rise to the canonical view that vitamin A indirectly promotes genomic responses
by serving as a precursor for retinoic acid-induced activation of nuclear receptor
complexes (Asson-Batres and Rochette-Egly 2014, 2016) However, current findings
strongly support the notion that vitamin A “…controls a larger spectrum of biological
activities than previously recognized” (Noy 2016). These actions include
(a) non-canonical, non-genomic, mechanisms of action of vitamin A via its
derivative, retinoic acid (Piskunov et al. 2014; Rochette-Egly 2015);
(b) effects of vitamin A, itself, in conjunction with retinol binding protein (RBP),
wherein holo-RBP binds to and activates the cytosolic membrane receptor, Stimulated by Retinoic Acid 6 (STRA6), which then activates the JAK-STAT pathway
and the transcription of genes beyond those that are activated by canonical retinoic
acid signaling (Noy 2016);
(c) the direct action of vitamin A on mitochondrial energetics and cytoplasmic
signaling (Hammerling 2016a, b); and
(d) the indirect effects of vitamin A on the epigenome through the actions of its
derivative, retinoic acid (Bar-El and Reifen 2017).
Future work is needed to elucidate these and other, as yet, unknown roles of
vitamin A and the consequences of deficiency.
References
Aberle SDB (1934) Neurological disturbances in rats reared on diets deficient in vitamin A. J Nutr
7:445–461
Asson-Batres MA, Rochette-Egly C (2014) The biochemistry of retinoic acid receptors I: structure,
activation, and function at the molecular level. Springer
Asson-Batres MA, Rochette-Egly C (2016) The biochemistry of retinoid signaling II: the physiology
of Vitamin A—Uptake, transport. Springer, Metabolism and Signaling
Asson-Batres MA, Smith WB (2006) Localization of retinaldehyde dehydrogenases and retinoid
binding proteins to sustentacular cells, glia, Bowman’s gland cells, and stroma: potential sites of
retinoic acid synthesis in the postnatal rat olfactory organ. J Comp Neurol 496:149–171