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mRNA concentrations of MIF in subcutaneous abdominal adipose cells are associated with adipocyte size and insulin action

International Journal of Obesity volume 33, pages 842–850 (2009)Cite this article

Abstract

Objective:

To determine whether the mRNA concentrations of inflammation response genes in isolated adipocytes and in cultured preadipocytes are related to adipocyte size and in vivo insulin action in obese individuals.

Design:

Cross-sectional inpatient study.

Subjects:

Obese Pima Indians with normal glucose tolerance.

Measurements:

Adipocyte diameter (by microscope technique; n=29), expression of candidate genes (by quantitative real-time PCR) in freshly isolated adipocytes (monocyte chemoattractant protein (MCP) 1 and MCP2, macrophage inflammatory protein (MIP) 1α, MIP1β and MIP2, macrophage migration inhibitory factor (MIF), tumor necrosis factor α, interleukin (IL) 6 and IL8; n=22) and cultured preadipocytes (MCP1, MIP1α, MIF, IL6 and matrix metalloproteinase 2; n=33) from subcutaneous abdominal adipose tissue (by aspiration biopsy, n=34), body fat by dual-energy X-ray absorptiometry, glucose tolerance by 75 g oral glucose tolerance test and insulin action by euglycemic-hyperinsulinemic clamp (insulin infusion rate 40 mU m−2 min−1) (all n=34).

Results:

MIF was the only gene whose expression in both freshly isolated adipocytes and cultured preadipocytes was positively associated with adipocytes diameter and negatively associated with peripheral and hepatic insulin action (all P<0.05). In multivariate analysis, the association between adipocyte MIF mRNA concentrations and adipocytes diameter was independent of the percentage of body fat (P=0.03), whereas adipocyte MIF mRNA concentrations, but not adipocyte diameter, independently predicted peripheral insulin action. The mRNA expression concentrations of the MIF gene in adipocytes were not associated with plasma concentrations of MIF, but were negatively associated with plasma adiponectin concentrations (P=0.004). In multivariate analysis, adipocyte MIF RNA concentrations (P=0.03) but not plasma adiponectin concentrations (P=0.4) remained a significant predictor of insulin action.

Conclusions:

Increased expression of MIF gene in adipose cells may be an important link between obesity characterized by enlarged adipocytes and insulin resistance in normal glucose tolerant people.

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Acknowledgements

This work was funded by the intramural research program of the NIDDK/NIH/DHHS. We gratefully acknowledge Thomas Brookshire, PA and nursing and dietary staffs of the NIH metabolic unit for the care of the volunteers, and Emma Rousseau and Shannon Parrington for excellent technical assistance. We are grateful to the members and leaders of the Gila River Indian Community for their continuing cooperation in our studies. We thank Dr Susanne Votruba for helpful comments on this article. Clinical trial registration number: NCT00410800.

Author information

Authors and Affiliations

  1. Obesity and Diabetes Clinical Research Section, NIDDK/NIH/DHHS, Phoenix, AZ, USA

    J Koska, C Trinidad, J C Bunt & P A Permana

  2. Phoenix Veterans Affairs Health Care System, Phoenix, AZ, USA

    J Koska & P A Permana

  3. Department of Internal Medicine, Division of Endocrinology, University of Tuebingen, Tuebingen, Germany

    N Stefan

  4. Pennington Biomedical Research Center, Baton Rouge, LA, USA

    S Dubois & E Ravussin

  5. Indiana University School of Medicine, 541 North Clinical Drive, Indianapolis, IN, USA

    R V Considine

  6. Graduate School of Medicine, Osaka University, 2-2-B5 Yamadaoka, Suita, Osaka, Japan

    T Funahashi

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Correspondence to J Koska.

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Supplementary Information accompanies the paper on International Journal of Obesity website (http://www.nature.com/ijo)

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Koska, J., Stefan, N., Dubois, S. et al. mRNA concentrations of MIF in subcutaneous abdominal adipose cells are associated with adipocyte size and insulin action. Int J Obes 33, 842–850 (2009). https://doi.org/10.1038/ijo.2009.106

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