title: Vitamin D and adipose tissue-more than storage.
abstract: The pandemic increase in obesity is inversely associated with vitamin D levels. While a higher BMI was causally related to lower 25-hydroxyvitamin D (25(OH)D), no evidence was obtained for a BMI lowering effect by higher 25(OH)D. Some of the physiological functions of 1,25(OH)2D3 (1,25-dihydroxycholecalciferol or calcitriol) via its receptor within the adipose tissue have been investigated such as its effect on energy balance, adipogenesis, adipokine, and cytokine secretion. Adipose tissue inflammation has been recognized as the key component of metabolic disorders, e.g., in the metabolic syndrome. The adipose organ secretes more than 260 different proteins/peptides. However, the molecular basis of the interactions of 1,25(OH)2D3, vitamin D binding proteins (VDBPs) and nuclear vitamin D receptor (VDR) after sequestration in adipose tissue and their regulations are still unclear. 1,25(OH)2D3 and its inactive metabolites are known to inhibit the formation of adipocytes in mouse 3T3-L1 cell line. In humans, 1,25(OH)2D3 promotes preadipocyte differentiation under cell culture conditions. Further evidence of its important functions is given by VDR knock out (VDR(-/-)) and CYP27B1 knock out (CYP27B1 (-/-)) mouse models: Both VDR(-/-) and CYP27B1(-/-) models are highly resistant to the diet induced weight gain, while the specific overexpression of human VDR in adipose tissue leads to increased adipose tissue mass. The analysis of microarray datasets from human adipocytes treated with macrophage-secreted products up-regulated VDR and CYP27B1 genes indicating the capacity of adipocytes to even produce active 1,25(OH)2D3. Experimental studies demonstrate that 1,25(OH)2D3 has an active role in adipose tissue by modulating inflammation, adipogenesis and adipocyte secretion. Yet, further in vivo studies are needed to address the effects and the effective dosages of vitamin D in human adipose tissue and its relevance in the associated diseases.
authors.affiliation: Department of Physiology, Institute of Biomedicine, University of Oulu Oulu, Finland ; Biocenter of Oulu, University of Oulu Oulu, Finland.
authors.forename: Shivaprakash J
authors.initials: SJ
authors.lastname: Mutt
authors.affiliation: School of Population Health and Sansom Institute, University of South Australia Adelaide, SA, Australia ; South Australian Health and Medical Research Institute Adelaide, SA, Australia ; Population, Policy and Practice, Institute of Child Health, University College London London, UK.
authors.forename: Elina
authors.initials: E
authors.lastname: Hyppönen
authors.affiliation: Department of Surgery, Oulu University Hospital, University of Oulu Oulu, Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Saarnio
authors.affiliation: Biocenter of Oulu, University of Oulu Oulu, Finland ; Unit of Primary Care, Institute of Health Sciences, University of Oulu, Oulu University Hospital Oulu, Finland ; Department of Children, Young People and Families, National Institute for Health and Welfare Oulu, Finland ; Department of Epidemiology and Biostatistics, and MRC-PHE Center for Environment and Health, School of Public Health, Imperial College London London, UK.
authors.forename: Marjo-Riitta
authors.initials: MR
authors.lastname: Järvelin
authors.affiliation: Department of Physiology, Institute of Biomedicine, University of Oulu Oulu, Finland ; Biocenter of Oulu, University of Oulu Oulu, Finland ; Medical Research Center Oulu and Oulu University Hospital Oulu, Finland.
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Herzig
keywords: 1,25-dihydroxycholecalciferol or calcitriol; adipogenesis; adipokines; adipose tissue; gene regulation; secretion; vitamin D binding protein