Vitamin A

Simulated microgravity induces a cellular regression of the mature phenotype in human primary osteoblasts.[Pubmed:29760957]

Cell Death Discov. 2018 May 10;4:59.

Decreased mechanical loading on bones, such as prolonged bed rest and microgravity during space flights, leads to the development of an osteoporotic-like phenotype. Although osteoblast hypo-functionality is reported to be involved in the progression of bone pathological conditions, the cellular mechanisms of this process remain largely unknown. The combined application of mass spectrometry "-omics" and histochemical and ultrastructural approaches have been employed to investigate the effects of the gravitational unloading on human bone-cell biology. Here we show, ex vivo, that simulated microgravity (Smug) on human primary osteoblasts (hpOB) induces an alteration of pro-osteogenic determinants (i.e., cell morphology and deposit of hydroxyapatite crystals), accompanied by a downregulation of adhesive proteins and bone differentiation markers (e.g., integrin beta-1, protein folding Crystallin Alpha B (CRYalpha-B), runt-related transcription factor 2 (RUNX-2), bone morphogenic protein-2 (BMP-2), and receptor activator of nuclear factor kappa-B ligand (RANK-L)), indicating an impairment of osteogenesis. Further, we observed for the first time that Smug can trigger a transition toward a mesenchymal-like phenotype, in which a mature osteoblast displays an hampered Vitamin A metabolism, loses adhesive molecules, gains mesenchymal components (e.g., pre-osteoblast state marker CD44), morphological protrusions (filopodium-like), enhances GTPase activities, which in turn allows it to acquire migrating properties. Although this phenotypic conversion is not complete and can be reversible, Smug environment proves a plasticity potential hidden on Earth. Overall, our results suggest that Smug can be a powerful physical cue for triggering ex vivo a dedifferentiation impulse on hpOBs, opening a new scenario of possible innovative therapeutical biomechanical strategies for the treatment of osteo-degenerative diseases.

Apocarotenoids: Emerging Roles in Mammals.[Pubmed:29751734]

Annu Rev Nutr. 2018 Aug 21;38:153-172.

Apocarotenoids are cleavage products of C40 isoprenoid pigments, named carotenoids, synthesized exclusively by plants and microorganisms. The colors of flowers and fruits and the photosynthetic process are examples of the biological properties conferred by carotenoids to these organisms. Mammals do not synthesize carotenoids but obtain them from foods of plant origin. Apocarotenoids are generated upon enzymatic and nonenzymatic cleavage of the parent compounds both in plants and in the tissues of mammals that have ingested carotenoid-containing foods. The best-characterized apocarotenoids are retinoids (Vitamin A and its derivatives), generated upon central oxidative cleavage of proVitamin A carotenoids, mainly beta-carotene. In addition to the well-known biological actions of Vitamin A, it is becoming apparent that nonretinoid apocarotenoids also have the potential to regulate a broad spectrum of critical cellular functions, thus influencing mammalian health. This review discusses the current knowledge about the generation and biological activities of nonretinoid apocarotenoids in mammals.

DHA upregulates FADS2 expression in primary cortical astrocytes exposed to vitamin A.[Pubmed:29750879]

Physiol Res. 2018 Aug 16;67(4):663-668. Epub 2018 May 10.

The fads2 gene encoding delta6-desaturase, the rate-limiting enzyme of the LCPUFA biosynthesis is expressed in astrocytes. Dietary fatty acids, which cross the blood-brain barrier, may regulate the transcription of lipogenic enzymes through activation of transcription factors such as peroxisome proliferator-activated receptors (PPARs). The PPARs form the transcription complex with retinoid X receptors (RXRs) that are activated by 9-cis retinoic acid, a metabolite of Vitamin A (VA). The study examines whether challenge of astrocytes with VA, prior 24-h treatment with palmitic acid (PA), alpha-linolenic acid (ALA) or docosahexaenoic acid (DHA) has the effect on the FADS2 expression. RT-qPCR showed that in astrocytes not challenged with VA, PA increased fads2 gene expression and DHA decreased it. However, in VA-primed astrocytes, PA doubled the FADS2 mRNA levels, while DHA increased fads2 gene expression, oppositely to non-primed cells. Furthermore, similar changes were seen in VA-primed astrocytes with regard to delta6-desaturase protein levels following PA and DHA treatment. ALA did not have any effect on the FADS2 mRNA and protein levels in either VA-primed or non-primed astrocytes. These findings indicate that in the presence of Vitamin A, DHA upregulates fads2 gene expression in astrocytes.

Comparative transcriptome analysis of rumen papillae in suckling and weaned Japanese Black calves using RNA sequencing.[Pubmed:29762736]

J Anim Sci. 2018 Jun 4;96(6):2226-2237.

The length and density of rumen papillae starts to increase during weaning and growth of ruminants. This significant development increases the intraruminal surface area and the efficiency of VFA (acetate, propionate, butyrate, etc.) uptake. Thus, it is important to investigate the factors controlling the growth and development of rumen papillae during weaning. This study aimed to compare the transcriptomes of rumen papillae in suckling and weaned calves. Total RNA was extracted from the rumen papillae of 10 male Japanese Black calves (5 suckling calves, 5 wk old; 5 weaned calves, 15 wk old) and used in RNA-sequencing. Transcript abundance was estimated and differentially expressed genes were identified and these data were then used in Ingenuity Pathway Analysis (IPA) to predict the major canonical pathways and upstream regulators. Among the 871 differentially expressed genes screened by IPA, 466 genes were upregulated and 405 were downregulated in the weaned group. Canonical pathway analysis showed that "atherosclerosis" was the most significant pathway, and "tretinoin," a derivative of Vitamin A, was predicted as the most active upstream regulator during weaning. Analyses also predicted IgG, lipopolysaccharides, and tumor-necrosis factor-alpha as regulators of the microbe-epithelium interaction that activates rumen-related immune responses. The functional category and the up-regulators found in this study provide a valuable resource for studying new candidate genes related to the proliferation and development of rumen papillae from suckling to weaning Japanese Black calves.

Comparative study of the nutritional status of vitamin A in pregnant women and in women who became pregnant or did not after Roux-en-Y gastric bypass.[Pubmed:29756978]

Nutr Hosp. 2018 Jan 18;35(2):421-427.

INTRODUCTION: the changes in digestive physiology after Roux-en-Y gastric bypass (RYGB), as well as pregnancy, maximizes the risk of Vitamin A deficiency (VAD) and both can result in harm to the mother and child health. OBJECTIVE: to compare the nutritional status of Vitamin A among women who became pregnant or did not after RYGB and in pregnant women who did not undergo surgery, and to assess the impact of VAD on the mother and child health. METHODS: this is a cross-sectional study of the analytical type. The women were divided into: group 1 (G1) with 80 pregnant women; group 2 (G2) with 40 pregnant women who had previously undergone RYGB, both in their third trimester of pregnancy; and group 3 (G3) with 77 non-pregnant women who had previously undergone RYGB. Serum concentrations of retinol and beta-carotene, night blindness (NB), gestational and neonatal intercurrences were investigated. The significance level adopted was p < 0.05. RESULTS: RYGB, per se,had a greater impact on the inadequacy of retinol, beta-carotene, and on the increased percentage of NB when compared to non-surgical pregnant women. When surgery was associated with pregnancy, more than 75% of inadequacy of retinol and beta-carotene was noted, as well as a higher percentage of individuals with NB. G2 also showed increased prevalence ratio for developing gestational and neonatal intercurrences, when compared to G1. CONCLUSION: RYGB provides greater negative impact on the nutritional status of Vitamin A compared to pregnancy, and surgery associated with pregnancy can create even greater risks.

Banana21: From Gene Discovery to Deregulated Golden Bananas.[Pubmed:29755496]

Front Plant Sci. 2018 Apr 26;9:558.

Uganda is a tropical country with a population in excess of 30 million, >80% of whom live in rural areas. Bananas (Musa spp.) are the staple food of Uganda with the East African Highland banana, a cooking banana, the primary starch source. Unfortunately, these bananas are low in pro-Vitamin A (PVA) and iron and, as a result, banana-based diets are low in these micronutrients which results in very high levels of inadequate nutrition. This inadequate nutrition manifests as high levels of Vitamin A deficiency, iron deficiency anemia, and stunting in children. A project known as Banana21 commenced in 2005 to alleviate micronutrient deficiencies in Uganda and surrounding countries through the generation of farmer- and consumer-acceptable edible bananas with significantly increased fruit levels of PVA and iron. A genetic modification approach was adopted since bananas are recalcitrant to conventional breeding. In this review, we focus on the PVA-biofortification component of the Banana21 project and describe the proof-of-concept studies conducted in Australia, the transfer of the technology to our Ugandan collaborators, and the successful implementation of the strategy into the field in Uganda. The many challenges encountered and the potential future obstacles to the practical exploitation of PVA-enhanced bananas in Uganda are discussed.

Dietary vitamin A impacts DNA methylation patterns of adipogenesis-related genes in suckling rats.[Pubmed:29758201]

Arch Biochem Biophys. 2018 Jul 15;650:75-84.

We previously showed that Vitamin A supplementation in early life impacts white adipose tissue (WAT) biology. We here studied the vitamin's effects on DNA methylation of genes crucial for WAT cell development, determination and metabolism. CpG promoter methylation and mRNA expression of Pparg, Zfp423, Pcna, and Rbp4 was compared in inguinal WAT of 21-day-old rats supplemented during the suckling period with vehicle (controls) or an emulsion of Vitamin A as retinyl ester (RE) or beta-carotene (BC). The methylation profile of promoters was affected by Vitamin A supplementation with pronounced differences between the RE and BC groups. In the RE group, hypermethylation of the Rbp4 (at multiple CpGs) and the Pparg2 (at a specific CpG) promoters and hypomethylation of the Pcna promoter (at multiple CpGs) was observed, together with inverse changes in gene expression levels. In the BC group, hypomethylation of the Rbp4 and hypermethylation of the Pcna promoter at distinct CpGs was observed, with no effects on gene expression. In both supplemention groups, hypomethylation and increased expression was found for Zfp423. Thus, modest Vitamin A supplementation in early postnatal life impacts methylation marks in developing WAT. Differential epigenetic effects of RE and BC in early life may affect adipose tissue programming activity.