Obesity associated with poor Vitamin D genes (VDR in this study) – Jan 2018

Vitamin D, Vitamin D Receptor, and Adipose Tissue: Focus on Cellular Mechanisms

Carmen J. Narvaez1, Donald G. Matthews1,2, JoEllen Welsh1
1 University at Albany, Rensselaer, NY, United States; 2 Oregon Health and Science University, Portland, OR, United States

VitaminDWiki

Fact: People with poor immune systems have been survived to become parents for 150 years
    poor hygene, no antibiotics, no vaccines, etc used toeliminatel 30% of potential parents
Appears that: More people now have poor immune systems
Fact: Poor Vitamin D genes are one aspect of a poor immune system
Fact: Obesity is associated with many different poor vitamin D genes
SPECULATION: Increased obesity is associated with poor vitamin D genetics


Items in both categories Obesity and Genetics are listed here:

Items in both categories Obesity and Vitamin D Receptor are listed here:

Items in both categories Obesity and Vitmin D Binding Protein are listed here:


Obesity is increasing globally (many charts, note: vitamin D can help) – Oct 2017
Obesity is associated with low Vitamin D (and treated by D as well) – Aug 2019 has the following
Fast weight loss by Obese Adults: Summary of the data as of Sept 2019
1) 50,000 IU Vitamin D weekly for at least 6 months
   If gut problems, should use a gut-friendly form of vitamin D
2) Add calorie restriction diet and light exercise after ~2 months*
   * Vitamin D levels must be above 30ng/ml to help with weight loss
   * Start losing weight 2 months sooner if take a 50,000 IU daily for a week
3) More weight loss if also add Magnesium or cofactors
   30% Improved Vitamin D response with Magnesium - a Vitamin D Cofactor
   Note: Magnesium reduces weight loss by itself as well
   20% improved vitamin D response if also add Omega-3 a Vitamin D Cofactor
  Note: Omega-3 reduces weight loss by itself as well
4) More weight loss if also improve activation of Vitamin D Receptor
   Vitamin D Receptor activator: 0-30% improved Vitamin D response
   Obesity 1.5 X more likely if poor Vitamin D Receptor – meta-analysis Nov 2019
Update Dec 2019 - Dr. Greger plant-based eating (not diet) for both weight loss and health.
  His book does not mention Vitamin D nor Adenovirus

 Download the PDF from ResearchGate via VitaminDWiki

Table of Contents

Storage of Vitamin D Metabolites in Adipose Tissue 584
Effect of Vitamin D on Adipogenesis at the Cellular Level 585
Model Systems for the Study of Adipogenesis 585
Effects of l,25(OH)2D Treatment and Vitamin D Receptor on Differentiation in 3T3-L1 Cells 586
Effects of l,25(OH)2D on Additional Established Rodent Cell Line Models of Adipogenesis 587
Vitamin D Signaling in Primary Cultures of Mesenchymal Cells 587
Role of the Vitamin D Receptor in Control of Adipogenesis 587
Effect of 1,25(OH)2D on Differentiation of Human Mesenchymal Precursors588
Impact of Vitamin D Signaling on Adiposity in Mouse Models 590
Genetically Engineered Mouse Models 590
Effect of Vitamin D Deficiency and Supplementation on Adiposity and Metabolism in Animal Models 591
Translational Considerations 592
Vitamin D Status and Body Weight: Insight Into Clinical Trials 592
Conclusions and Future Directions 593


Adipocytes function in storage of energy reserves, secretion of adipokines that regulate appetite, and control of thermogenesis. The major form of adipose tissue is termed white adipose tissue (WAT) and is located in subcutaneous and visceral depots. Development and maintenance of WAT is dependent on the nuclear receptor peroxisome prolifera- tor-activated receptor y (PPARy), which drives adipogenesis (generation of new adipocytes from mesenchymal precursors) and regulates fatty acid storage and glucose metabolism. PPARy regulates multiple target genes essential for adipocyte differentiation, lipid metabolism, and glucose homeostasis, as well as the expression of adipokines and cytokines secreted from adipose tissue. Brown adipose tissue (BAT) is a unique type of adipose tissue present in mammals that functions in body temperature regulation. Activated BAT uniquely expresses an “uncoupling protein" (UCP1) within the inner mitochondrial membrane, which uncouples substrate oxidation from ATP synthesis, leading to increased fuel oxidation and thermogenesis. The vitamin D receptor (VDR) and vitamin D-metabolizing enzymes_(CYP24A1, CYP27B1) are expressed in adipose tissue, and vitamin D signaling has been shown to alter the differentiation and phenotype of both WAT and BAT adipocytes and to modulate adiposity and energy metabolism in vivo. Examples of recently uncovered mechanisms that contribute to the effects

CONCLUSIONS AND FUTURE DIRECTIONS

In summary, adipose tissue has long been recognized as a major site of vitamin D storage, and new technologies have facilitated quantitation of the amount of vitamin D and 25(OH)D in adipose tissue depots. Although it appears likely that vitamin D storage and release is regulated (for example, during physiological states such as puberty, pregnancy, and aging), but virtually nothing is known about the mechanisms by which this might be achieved. Understanding regulatory signals and genetic determinants of vitamin D storage might provide insight into how pathological conditions such as obesity and metabolic syndrome alter the process, leading to lower serum 25(OH)D in such conditions. With respect to adipose tissue as a target for vitamin D, both mesenchymal precursors and mature adipocytes express the VDR and the major vitamin D-metabolizing enzymes [24,73,111]. Direct actions of 25(OH)D, 1,25(OH)2D, and VDR on adipogenic differentiation and gene expression have been documented, although the effects differ with model system. Animal studies support a modulatory role for dietary vitamin D and VDR activity in control of body weight, but much contradictory data exist, and detailed mechanisms are lacking. It is likely that vitamin D has distinct effects on mesenchymal precursors, preadipocytes, and mature adipocytes, which could account for much of the variability derived from in vitro studies and differences in the phenotypes of genetically engineered mice. In addition to direct effects on adipose tissue, it is quite clear that vitamin D signaling integrates pathways in different tissues (including muscle, liver, bone, and possibly brain) that influence metabolism and energy expenditure and indirectly alter the balance of lipogenesis and lipolysis in adipose tissue. Although obesity in humans is consistently associated with low serum 25(OH) D, most studies have failed to detect significant effects of vitamin D supplementation on overall body weight, although some data support beneficial effects of supplementation on fat mass, waist circumference, insulin sensitivity, and/or inflammation. As recent studies have demonstrated that vitamin D supplementation alters adipose tissue gene expression 112, and VDR has been identified as a gene induced by insulin in "healthy" obesity [113], further mechanistic research into the role of vitamin D and its receptor in adipose tissue biology is critical to resolve the current inconsistencies in this field and to facilitate translational impact.

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