CMO1 Deficiency Abolishes Vitamin A Production from β-Carotene and Alters Lipid Metabolism in Mice

Carotenoids are currently investigated regarding their potential to lower the risk of chronic disease and to combat vitamin A deficiency in humans. These plant-derived compounds must be cleaved and metabolically converted by intrinsic carotenoid oxygenases to support the panoply of vitamin A-dependent physiological processes. Two different carotenoid-cleaving enzymes were identified in mammals, the classical carotenoid-15,15′-oxygenase (CMO1) and a putative carotenoid-9′,10′-oxygenase (CMO2). To analyze the role of CMO1 in mammalian physiology, here we disrupted the corresponding gene by targeted homologous recombination in mice. On a diet providing β-carotene as major vitamin A precursor, vitamin A levels fell dramatically in several tissues examined. Instead, this mouse mutant accumulated the provitamin in large quantities (e.g. as seen by an orange coloring of adipose tissues). Besides impairments in β-carotene metabolism, CMO1 deficiency more generally interfered with lipid homeostasis. Even on a vitamin A-sufficient chow, CMO1-/- mice developed a fatty liver and displayed altered serum lipid levels with elevated serum unesterified fatty acids. Additionally, this mouse mutant was more susceptible to high fat diet-induced impairments in fatty acid metabolism. Quantitative reverse transcription-PCR analysis revealed that the expression of peroxisome proliferator-activated receptor γ-regulated marker genes related to adipogenesis was elevated in visceral adipose tissues. Thus, our study identifies CMO1 as the key enzyme for vitamin A production and provides evidence for a role of carotenoids as more general regulators of lipid metabolism.

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Role of vitamin A deficiency in the pathogenesis of myeloproliferative disorders

Blood ◽

10.1182/blood.v98.5.1636 ◽

2001 ◽

Vol 98 (5) ◽

pp. 1636-1637

Author(s):

Muttuswamy Sivakumaran

Keyword(s):

Vitamin A ◽

Vitamin A Deficiency ◽

Myeloproliferative Disorders

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Genotype Effects on β-Carotene Conversion to Vitamin A: Implications on Reducing Vitamin A Deficiency in the Philippines

Food and Nutrition Bulletin ◽

10.1177/03795721211060229 ◽

2021 ◽

pp. 037957212110602

Author(s):

Mark Pretzel P. Zumaraga ◽

Jose Maria Reynaldo Apollo Arquiza ◽

Mae Anne Concepcion ◽

Leah Perlas ◽

Ma. Neda Alcudia-Catalma ◽

...

Keyword(s):

Vitamin A ◽

Children And Adolescents ◽

Vitamin A Deficiency ◽

The Philippines ◽

Fisher Exact Test ◽

National Capital Region ◽

Nutrition Survey ◽

Vitamin A Status ◽

Genotype Frequencies

Background: The study aimed to identify two beta-carotene 15,15′-monooxygenase (BCMO1) mutations, namely R267S and A379V, and determine their association with vitamin A status among Filipinos 6 to 19 years old respondents of the 2013 Philippine National Nutrition Survey living in the National Capital Region. Materials and Methods: This study followed cross-sectional design. Whole blood specimen was collected in the morning and was used as source of genomic DNA and serum for retinol concentration determination. Fisher exact test was performed to determine whether genotype frequencies were associated to retinol concentrations/vitamin A deficiency status. A level of P < .05 was identified as significant. Results: A total of 693 Filipino children and adolescents were included. Of the 693, there were at least 7.6% who bears the combined mutations for R267S + A379V. Association analysis showed that an inverse relationship exists between the A379V TT variant and vitamin A status. Although the exact role of these identified polymorphisms on retinol/carotenoid metabolism need to be confirmed in dedicated functional studies. Conclusion: This study has identified for the first time the presence of 2 nonsynonymous genetic variants/mutations in the coding region of BCMO1 gene. Interestingly, one of these two variants, the A379V T, was found to be associated with vitamin A status. It is, therefore, warranted to investigate the role of BCMO1 variants for the success of supplementation programs and fortification efforts among vulnerable populations in this region. Genetic variability should be considered for future provitamin A supplementation recommendations among children and adolescents in the Philippines.

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Nutritional enhancement of Ghanaian weaning foods using the orange flesh sweetpotato (Ipomea batatas)

African Journal of Food, Agriculture, Nutrition and Development ◽

10.18697/ajfand.65.13190 ◽

2014 ◽

Vol 14 (65) ◽

pp. 9236-9256

Author(s):

EA Bonsi ◽

◽

WA Plahar ◽

R Zabawa ◽

◽

...

Keyword(s):

Vitamin A ◽

Sweet Potato ◽

Nutritive Value ◽

Vitamin A Deficiency ◽

Consumer Acceptability ◽

Weaning Food ◽

Nutrient Density ◽

Weaning Foods ◽

Maize Meal ◽

Β Carotene

Vitamin A deficiency (VAD) is a public health problem in Ghana. Research on the orange flesh sweet potato root has been given prominence because of its high β - carotene content as a means to enhance the nutritive value and vitamin A content of the traditional diets of Ghanaian children as a long -term intervention towards combating VAD. Two Ghanaian cereal -legume weaning foods: roasted maize- soy blend and fermented maize -soy blend were added to Orange Flesh Sweet potato (O FS) flour from the variety, Beauregard, to develop four weaning food formulations . To each product formulation preparation, 25% and 50% OFS flour was added to the basic cereal - legume meals , and mixed thoroughly. The four weaning formulations were evaluated for chemical composition, sensory characteristics and consumer acceptability. All samples had a range of protein (12.1% - 15%), fat (4.8% - 6.4%), carbohydrate (71.1% – 75.1%), energy (380 - 390 kcal/100g) and minerals (calcium, iron and phosphorus) to ensure good nutrient density, while the moisture content was low (5.3% - 6.1%) for storage stability. The contribution of β -carotene ( 55.18 –115.55 ug/g) by the OFS in the formulations further enhanced the nutritive value of all the blends and is enough to meet the daily β -carotene needs of the children ( 1-6 yrs of 400 -450ug/100g). A higher level of β -carotene was seen in the roasted maize meal weaning foods which make s them a better potential blend for combating VAD. Also, sensory evaluation of the products indicated the highest consumer acceptability score (87%) for the roasted maize meal porridge formulation containing 25% OFS . It is, therefore , concluded that OFS flour has the potential to be used at 25% replacement level in the soy- fortified roasted maize meal formulation, and OFS is a useful ingredient with the potential to improve the β -carotene or vitamin A content of such formulations . This will help alleviate vitamin A deficiency of children in Ghana and other countries with similar problems . It is , therefore, recommended that the orange flesh sweet potato flour be used by mothers as an entry point for enhancing the traditional weaning food preparations .

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Hypertrophy of Adipose Tissues in Quail Embryos by in ovo Injection of All-Trans Retinoic Acid

Frontiers in Physiology ◽

10.3389/fphys.2021.681562 ◽

2021 ◽

Vol 12 ◽

Author(s):

Dong-Hwan Kim ◽

Joonbum Lee ◽

Sanggu Kim ◽

Hyun S. Lillehoj ◽

Kichoon Lee

Keyword(s):

Retinoic Acid ◽

Vitamin A ◽

Marker Gene ◽

Marker Genes ◽

Health Issues ◽

Fat Cell ◽

In Ovo ◽

Adipose Tissues ◽

Trans Retinoic Acid ◽

All Trans Retinoic Acid

Excessive adipose accretion causes health issues in humans and decreases feed efficiency in poultry. Although vitamin A has been known to be involved in adipogenesis, effects of all-trans retinoic acid (atRA), as a metabolite of vitamin A, on embryonic adipose development have not been studied yet. Avian embryos are developing in confined egg environments, which can be directly modified to study effects of nutrients on embryonic adipogenesis. With the use of quail embryos, different concentrations of atRA (0 M to 10 μM) were injected in ovo at embryonic day (E) 9, and adipose tissues were sampled at E14. Percentages of fat pad weights in embryo weights were significantly increased in the group injected with 300 nM of atRA. Also, among three injection time points, E5, E7, or E9, E7 showed the most significant increase in weight and percentage of inguinal fat at E14. Injection of atRA at E7 increased fat cell size in E14 embryos with up-regulation of pro-adipogenic marker genes (Pparγ and Fabp4) and down-regulation of a preadipocyte marker gene (Dlk1) in adipose tissues. These data demonstrate that atRA promotes hypertrophic fat accretion in quail embryos, implying important roles of atRA in embryonic development of adipose tissues.

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Cassava with enhanced β-carotene maintains adequate vitamin A status in Mongolian gerbils (Meriones unguiculatus) despite substantial cis-isomer content

British Journal Of Nutrition ◽

10.1017/s0007114508184720 ◽

2009 ◽

Vol 102 (3) ◽

pp. 342-349 ◽

Cited By ~ 25

Author(s):

Julie A. Howe ◽

Bussie Maziya-Dixon ◽

Sherry A. Tanumihardjo

Keyword(s):

Vitamin A ◽

Vitamin A Deficiency ◽

Meriones Unguiculatus ◽

Provitamin A ◽

Carotenoid Content ◽

Mongolian Gerbils ◽

Serum Retinol ◽

Vitamin A Status ◽

Isomer Content ◽

Β Carotene

Efforts to increase β-carotene in cassava have been successful, but the ability of high-β-carotene cassava to prevent vitamin A deficiency has not been determined. Two studies investigated the bioefficacy of provitamin A in cassava and compared the effects of carotenoid content and variety on vitamin A status in vitamin A-depleted Mongolian gerbils (Meriones unguiculatus). Gerbils were fed a vitamin A-free diet 4 weeks prior to treatment. In Expt 1, treatments (ten gerbils per group) included 45 % high-β-carotene cassava, β-carotene and vitamin A supplements (intake matched to high-β-carotene cassava group), and oil control. In Expt 2, gerbils were fed cassava feeds with 1·8 or 4·3 nmol provitamin A/g prepared with two varieties. Gerbils were killed after 4 weeks. For Expt 1, liver vitamin A was higher (P < 0·05) in the vitamin A (1·45 (sd 0·23) μmol/liver), lower in the control (0·43 (sd 0·10) μmol/liver), but did not differ from the β-carotene group (0·77 (sd 0·12) μmol/liver) when compared with the high-β-carotene cassava group (0·69 (sd 0·20) μmol/liver). The bioconversion factor was 3·7 μg β-carotene to 1 μg retinol (2 mol:1 mol), despite 48 % cis-β-carotene [(Z)-β-carotene] composition in cassava. In Expt 2, cassava feed with 4·3 nmol provitamin A/g maintained vitamin A status. No effect of cassava variety was observed. Serum retinol concentrations did not differ. β-Carotene was detected in livers of gerbils receiving cassava and supplements, but the cis-to-trans ratio in liver differed from intake. Biofortified cassava adequately maintained vitamin A status and was as efficacious as β-carotene supplementation in the gerbil model.

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Effect of Drying on β-Carotene, α Carotene, Lutein and Zeaxanthin Content in Vegetables and Its Application for Vegetable Seasoning

E3S Web of Conferences ◽

10.1051/e3sconf/202014102007 ◽

2020 ◽

Vol 141 ◽

pp. 02007

Author(s):

Kullamethee Piyarach ◽

Kamnerd Nipawan ◽

Chumphukhaw Chadapon ◽

Suwannasit Daluwan ◽

Rotjanapun Kunjana

Keyword(s):

Vitamin A ◽

Vitamin A Deficiency ◽

Cost Effective ◽

Food Preservation ◽

Daily Consumption ◽

Overall Acceptability ◽

Chinese Kale ◽

Pepper Powder ◽

Air Dryer ◽

Β Carotene

In plant based food with dark-green, yellow and orange color, beta (β)-carotene, alpha (α)-carotene, lutein and zeaxanthin are predominating carotenoids contributing to an eyesight improvement. Among food preservation methods, drying using cabinet hot air dryer is one of the most cost-effective options and therefore, this investigation was aimed to study the carotenoids content in vegetables after drying and optimize the vegetable seasoning product. Based on customer survey, carrot, pumpkin, Chinese kale and long coriander were selected for the experiment, accessibility and have met the requirement of final moisture content, less than 10%. Our results demonstrated that drying period of sliced carrots and pumpkins was 360 min, while in Chinese kale and long coriander was 240 min. Amounts of carotenoids in carrot and long coriander were greatly remaining after drying. Drying of Chinese kale had little effect on carotenoids content. While, dried pumpkin may cause a major loss of β-,α-carotene and lutein content over 50%. Regarding to development of vegetable seasoning powder, Just about right and Hedonic 9 point tests were used for a sensory evaluation. The optimal seasoning formula consisted of 66. 8% mixed dried ground vegetables, 13.4% sugar, 8.8% salt, 6.7% garlic powder, and 4.3% white pepper powder. The overall acceptability of the product was rated as moderately liked, containing β-carotene, α-carotene, lutein and zeaxanthin content as 178.04±3.39, 58.81±1.83, 158.89±4.16, 0.98±0.01 μg/g, respectively (vitamin A approximately 29.67 μg RE/g). Fortification of vegetable seasoning powder for daily consumption may improve the eye vision and reduce the rate of vitamin A deficiency.

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A new approach to the assessment of marginal vitamin A deficiency in children in suburban Guwahati, India: hydrolysis of retinoyl glucuronide to retinoic acid

British Journal Of Nutrition ◽

10.1017/s0007114508047739 ◽

2008 ◽

Vol 101 (6) ◽

pp. 794-797 ◽

Cited By ~ 3

Author(s):

Pulin C. Sarma ◽

Bhabesh C. Goswami ◽

Krishna Gogoi ◽

Harsha Bhattacharjee ◽

Arun B. Barua

Keyword(s):

Retinoic Acid ◽

Vitamin A ◽

Vitamin A Deficiency ◽

Serum Retinol ◽

Serum Samples ◽

Group I ◽

High Prevalence ◽

Hydrolysis Of ◽

Β Carotene

The objective of the present study was to determine marginal vitamin A deficiency (VAD) by testing the hydrolysis of retinoyl glucuronide (RAG) to retinoic acid (RA) in children. Previous studies in rats showed that hydrolysis occurred when rats were vitamin A deficient. Children (n 61) aged 3–18 years, were divided into two groups, I and II. Blood was collected from the children in Group I (n 19) who were not dosed with RAG. Children in Group II (n 42) were administered all-trans retinoyl glucuronide (RAG) orally, and blood was collected 4 h after the dose. All serum samples were analysed for retinoids and carotenoids. RA was detected in serum only when serum retinol was < 0·85 μmol/l. Thus, hydrolysis of RAG to RA occurred in children with VAD or marginal VAD. Serum retinol was < 0·35 μmol/l in twenty-one children, 0·35–0·7 μmol/l in twenty-three children, 0·7–0·9 μmol/l in eleven children and >1 μmol/l in six children. Mean serum retinol in sixty-one children was 0·522 (sd 0·315) μmol/l. Mean β-carotene (0·016 (sd 0·015) μmol/l) was far below normal compared to the level of lutein (0·176 (sd 0·10) μmol/l) in sixty-one children. A low β-carotene level might be due to a low intake of carotene but high demand for vitamin A. The RAG hydrolysis test may prove to be a useful approach for the determination of marginal VAD with no clinical or subclinical signs of VAD. High prevalence of VAD amongst certain communities in Assam cannot be ruled out.

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A Comparison of Retinyl Palmitate and Red Palm Oil β-Carotene as Strategies to Address Vitamin A Deficiency

Nutrients ◽

10.3390/nu5083257 ◽

2013 ◽

Vol 5 (8) ◽

pp. 3257-3271 ◽

Cited By ~ 17

Author(s):

Ellie Souganidis ◽

Arnaud Laillou ◽

Magali Leyvraz ◽

Regina Moench-Pfanner

Keyword(s):

Vitamin A ◽

Palm Oil ◽

Vitamin A Deficiency ◽

Retinyl Palmitate ◽

Red Palm Oil ◽

Β Carotene

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Migration, Marital Status and Smoking as Risk Determinants of Cancer

Scandinavian Journal of Social Medicine ◽

10.1177/140349488701500203 ◽

1987 ◽

Vol 15 (2) ◽

pp. 67-72 ◽

Cited By ~ 10

Author(s):

Leena Tenkanen ◽

Lyly Teppo

Keyword(s):

Risk Factors ◽

Lung Cancer ◽

High Risk ◽

Vitamin A ◽

Marital Status ◽

Psychosocial Stress ◽

Vitamin A Deficiency ◽

Cancer Epidemiology ◽

Risk Determinants

To study the importance of migration to urban area, marital status and smoking as risk factors in cancer, a cohort of 4475 Finnish men was followed up for the occurrence of cancer during the period 1964–1980. Of particular interest was the interaction of migration or marital status with smoking. For cancers at all sites, not married urbanized smoking men had the greatest risk, followed by not married native urban smokers. This pattern was mainly due to high risk of cancers of the lung and larynx among the urbanized men, with a risk peak among urbanized not married smokers. The pattern persisted even when the amount smoked was allowed for. The importance in lung cancer epidemiology of vitamin A deficiency, occupation and psychosocial stress was discussed, and some support was found for the role of psychosocial stress in both the migration and the marital status factors.

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