Vitamin D gets trapped in fat cells - improved understanding - Holick

Created January 2025

Interaction of Vitamin D-BODIPY With Fat Cells and the Link to Obesity-associated Vitamin D Deficiency

Anticancer Research January 2025, 45 (1) 55-63; DOI: https://doi.org/10.21873/anticanres.17392

NAZLI UÇAR, JUDE T. DEENEY, R. TAYLOR PICKERING, TING-YU FAN, RALF LOO, PETER M. MUELLER and MICHAEL F. HOLICK

Background/Aim: Obese individuals often exhibit vitamin D deficiency, potentially due to sequestration in fat cells. Little is known about how vitamin D3 enters adipocytes and associates with the intracellular lipid droplet.

Materials and Methods: Newly differentiated human and mouse (3T3-L1) adipocytes and primary mouse adipocytes were treated with vitamin D3 covalently linked to green fluorescent BODIPY (VitD-B) or Green BODIPY (GB) as control. Cells were exposed to 10-100 nM concentrations for various lengths of time (1-48 h). Fluorescence microscopy assessed vitamin D distribution.

Results: VitD-B demonstrated stable incorporation into adipocytes without enzymatic cleavage, as HPLC showed no free vitamin D3 after 72 h. Fluorescence microscopy showed GB uptake was rapid and persisted for 48 h. VitD-B uptake was more gradual compared to GB in the human and 3T3-L1 adipocytes. Primary mouse adipocytes exhibited similar uptake patterns, with VitD-B appearing within 1 h and fluorescence intensity increasing 1.2-fold at 8 h and 5.7-fold at 24 h. GB exhibited rapid fluorescence uptake in these same cells, 29-fold higher than VitD-B at 1 h. At 24 h, some VitD-B treated cells exhibited greater fluorescence intensity around the surface of the lipid droplets, which was not observed in GB. Isolated lipid droplets exhibited rapid and immediate uptake of both VitD-B and GB, indicating a strong affinity for these lipid structures. The time-dependent accumulation of vitamin D3 in human adipocytes mirrored VitD-B uptake.

Conclusion: VitD-B is a reliable proxy for studying the dynamics of vitamin D3 uptake in adipocytes.

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Main points of the study by Perplexity AI - Jan 2024

This research paper investigates how vitamin D interacts with fat cells (adipocytes), with key findings organized as follows:

Methodology and Tools

  • Researchers developed a fluorescent-labeled vitamin D (VitD-B) to track its movement in fat cells

  • The study examined both human and mouse fat cells, including cultured cells and primary cells extracted from tissue

  • VitD-B proved stable over 72 hours with no breakdown, making it a reliable research tool

    Key Findings

    Uptake Patterns

  • VitD-B enters fat cells gradually over time, unlike the control substance (GB) which enters quickly

  • After 24 hours, some cells showed a distinctive "halo" pattern of vitamin D around their lipid droplets

  • The time-dependent accumulation of regular vitamin D matched the pattern seen with VitD-B

    Cell Type Comparisons

  • Similar uptake patterns were observed across different cell types:

    • Human fat cells

    • Mouse 3T3-L1 cells

    • Primary mouse fat cells

    Clinical Implications

    Obesity Connection

  • The research helps explain why obese individuals often have vitamin D deficiency

  • As fat tissue increases, more vitamin D becomes trapped in fat cells

  • This sequestration reduces vitamin D's availability to the rest of the body

    Research Limitations

  • The study was limited to 48 hours, preventing understanding of long-term effects

  • In vitro models may not fully replicate the complexity of living tissue

  • The isolation process for lipid droplets may have disrupted some cellular mechanisms

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