Gene Expression Pattern in Response to Cholecalciferol Supplementation Highlights Cubilin as a Major Protein of 25(OH)D Uptake in Adipocytes and Male Mice White Adipose Tissue
Bonnet L, Karkeni E, Couturier C, Astier J, Dalifard J, Defoort C, Svilar L, Martin JC, Tourniaire F, Landrier JF
Endocrinology · 19 citations
Review labels
Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.
How it was studied
- Design
- Animal study (classified by our AI screen)
- Studied in
- People, plus animal or lab work
- Main outcome
- Mechanisms only
Who paid for it
- Funding
- Independent funding
- Government
- Institut National de la Santé et de la Recherche Médicale
- Government
- Institut National de la Recherche Agronomique
Based on 2 listed funder(s).
Publication
- Published
- 2017-11-24 · Endocrinology · vol. 159 · issue 2 · pp. 957–966
- Publisher
- Oxford University Press
- Cited
- 31 citations · more than 88% of similar papers · 2.3× the field average
- References
- 49 works
- Access
- Free to read
- Research areas
- Vitamin D Research Studies · Vitamin C and Antioxidants Research · Stress Responses and Cortisol
- Keywords
- Endocrinology, Cholecalciferol, Internal medicine, Biology, Calcitriol receptor, Adipose tissue, CYP24A1, White adipose tissue, Vitamin D and neurology, Gene expression, Biochemistry, Gene, Medicine
- MeSH
- cells, cultured, 3t3-l1 cells, adipocytes, animals, mice, inbred c57bl, humans, mice, cholecalciferol, vitamin d, receptors, cell surface, receptors, calcitriol, gene expression profiling, gene expression regulation, dietary supplements, female, male, lipid metabolism, adipose tissue, white
10 authors
From FR
- L BonnetInserm; Aix-Marseille Université; Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement; Unité de recherche sur les maladies cardiovasculaires et métaboliques
- Esma KarkeniInserm; Aix-Marseille Université; Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement; Unité de recherche sur les maladies cardiovasculaires et métaboliques
- Charlène CouturierInserm; Aix-Marseille Université; Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement; Unité de recherche sur les maladies cardiovasculaires et métaboliques
- Julien AstierInserm; Aix-Marseille Université; Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement; Unité de recherche sur les maladies cardiovasculaires et métaboliques
- Julie DalifardInserm; Aix-Marseille Université; Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement; Unité de recherche sur les maladies cardiovasculaires et métaboliques
- Catherine DefoortInserm; Aix-Marseille Université; Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement; Unité de recherche sur les maladies cardiovasculaires et métaboliques
Abstract
It is well established that the active form of vitamin D (i.e., 1,25-dihydroxyvitamin D [1,25(OH)2D]) regulates the expression of genes involved in its own metabolism and transport in the kidney and possibly in the liver. However, little is known about the transcriptional impact of cholecalciferol supplementation on white adipose tissue (WAT) and adipocytes, which are a major site of vitamin D and 25-hydroxyvitamin D [25(OH)D] storage in the organism. To fill this gap, we investigated the impact of cholecalciferol supplementation in WAT via a panel of genes coding for enzymes and proteins involved in vitamin D metabolism and uptake. Mice supplemented with cholecalciferol (15,000 IU/kg of body weight per day) for 4 days showed decreased messenger RNA (mRNA) levels of proteins involved in cholecalciferol metabolism (Cyp24a1, Cyp27a1) and decreased cubilin mRNA levels in WAT. These data were partly confirmed in 3T3-L1 adipocytes incubated with 1,25(OH)2D. The downregulation of cubilin mRNA observed in WAT and in 3T3-L1 was confirmed at the protein level in WAT and at the mRNA level in human primary adipocytes. Vitamin D receptor (VDR) agonist (EB1089) and RNA interference approaches demonstrated that VDR was involved in this regulation. Furthermore, chemical inhibitor and RNA inference analysis demonstrated that cubilin was involved in 25(OH)D uptake by adipocytes. This study established an overall snapshot of the genes regulated by cholecalciferol in mouse WAT and cell-autonomously in adipocytes. We highlighted that the regulation of cubilin expression was mediated by a VDR-dependent mechanism, and we demonstrated that cubilin was involved in 25(OH)D uptake by adipocytes.
Abstract via Europe PMC. Copyright remains with the authors or publisher.
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