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Differential effects of 1α,25-dihydroxycholecalciferol on MCP-1 and adiponectin production in human white adipocytes

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Abstract

Background/aim

Obesity is characterized by a low-grade inflammation in white adipose tissue (WAT), which promotes insulin resistance. Low serum levels of 1α,25-dihydroxycholecalciferol (DHCC) associate with insulin resistance and higher body mass index although it is unclear whether vitamin D supplementation improves insulin sensitivity. We investigated the effects of DHCC on adipokine gene expression and secretion in adipocytes focusing on two key factors with pro-inflammatory [monocyte chemoattractant protein-1 (MCP-1/CCL2)] and anti-inflammatory [adiponectin (ADIPOQ)] effects.

Methods

Pre-adipocytes were isolated from human subcutaneous WAT and cultured until full differentiation. Differentiated adipocytes were either pre-treated with DHCC (10−7 M) and subsequently incubated with tumor necrosis factor-α (TNFα, 100 ng/mL) or concomitantly incubated with TNFα/DHCC. MCP1 and adiponectin mRNA expression was measured by RT–PCR and protein release by ELISA.

Results

DHCC was not toxic and did not affect adipocyte morphology or the mRNA levels of adipocyte-specific genes. TNFα induced a significant increase in CCL2 mRNA and protein secretion, while DHCC alone reduced CCL2 mRNA expression (~25%, p < 0.05). DHCC attenuated TNFα-induced CCL2 mRNA expression in both pre-incubation (~15%, p < 0.05) and concomitant (~60%, p < 0.01) treatments. TNFα reduced ADIPOQ mRNA (~80%) and secretion (~35%). DHCC alone decreased adiponectin secretion to a similar degree (~35%, p < 0.05). Concomitant treatment with DHCC/TNFα for 48 h had an additive effect, resulting in a pronounced reduction in adiponectin secretion (~70%).

Conclusions

DHCC attenuates MCP-1 and adiponectin production in human adipocytes, thereby reducing the expression of both pro- and anti-inflammatory factors. These effects may explain the difficulties so far in determining the role of DHCC in insulin sensitivity and obesity in humans.

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Acknowledgments

This work has been supported by Nordic Centre of Excellence on “Systems biology in controlled dietary interventions and cohort studies, SYSDIET (No. 070014)”. MR, PA, and ID are supported by grants from the Swedish Research Council. MR and PA are also supported by grants from the NovoNordisk Foundation and the Swedish Diabetes Fund.

Conflict of interest

All the authors have read and approved submission of the manuscript and declare no conflict of interest.

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Authors and Affiliations

  1. Department of Medicine Huddinge, Lipid Laboratory, Karolinska Institutet, NVS, Karolinska University Hospital Huddinge, 141 86, Stockholm, Sweden

    Silvia Lorente-Cebrián, Anna Eriksson, Niklas Mejhert, Ingrid Dahlman, Gaby Åström, Eva Sjölin, Kerstin Wåhlén, Jurga Laurencikiene, Peter Arner & Mikael Rydén

  2. Department of Physiology, Institute of Biomedicine, Faculty of Medicine, Biomedicum Helsinki, Haartmaninkatu 8, 00029, Helsinki, Finland

    Thomas Dunlop

  3. Department of Biosciences, University of Eastern Finland, 70211, Kuopio, Finland

    Carsten Carlberg

  4. Department of Plastic Surgery, Akademikliniken, 115 42, Stockholm, Sweden

    Per Hedén

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  1. Silvia Lorente-Cebrián
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Corresponding author

Correspondence to Silvia Lorente-Cebrián.

Additional information

S. Lorente-Cebrián and A. Eriksson contributed equally to this work.

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Lorente-Cebrián, S., Eriksson, A., Dunlop, T. et al. Differential effects of 1α,25-dihydroxycholecalciferol on MCP-1 and adiponectin production in human white adipocytes. Eur J Nutr 51, 335–342 (2012). https://doi.org/10.1007/s00394-011-0218-z

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