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Integrative Biology

Liver, but not adipose tissue PEDF gene expression is associated with insulin resistance

International Journal of Obesity volume 37, pages 1230–1237 (2013)Cite this article

Subjects

Abstract

Objective:

Recent studies linked circulating pigment epithelium-derived factor (PEDF) to obesity-associated insulin resistance, but the main source of circulating PEDF is unknown. We aimed to investigate liver and adipose tissue PEDF gene expression in association with obesity and insulin resistance.

Design, subjects and methods:

Three (two cross-sectional and one longitudinal) independent cohorts have been studied, for adipose tissue (n=80 and n=30) and liver gene expression (n=32 and n=14). Effects of high glucose and cytokines on HepG2 cell line were also investigated. PEDF gene expression and circulating PEDF were analyzed using real-time PCR and ELISA, respectively.

Results:

In a first cohort of subjects, PEDF relative gene expression was higher in subcutaneous (SC) than in omental (OM) adipose tissue (P<0.0001) being also higher in mature adipocytes compared with stromo-vascular cells (P<0.0001). However, OM PEDF relative gene expression was decreased in morbidly obese subjects (P=0.01). Both OM PEDF and OM PEDF receptor (PEDFR) correlated positively with lipogenic and lipolytic genes, and with genes implicated in the lipid vacuole formation. Circulating PEDF levels were not associated with fat PEDF gene expression. In the second cohort, SC PEDF was decreased in subjects with type 2 diabetes and did not change significantly after weight loss. We next explored circulating PEDF in association with markers of liver-related insulin resistance injury (alanine aminotransferase, r=0.59, P=0.001). Interestingly, liver PEDF gene expression increased with obesity and insulin resistance in men, being significantly associated with fasting glucose and glycated hemoglobin in two independent cohorts. In fact, high glucose led to increased PEDF in HepG2 cells, while inflammatory stimuli present in the adipose tissue environment downregulated PEDF.

Conclusion:

Liver, but not adipose tissue, might be the source of increased circulating PEDF linked to insulin resistance.

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Acknowledgements

This work was partially supported by research grants from the Ministerio de Educación y Ciencia (SAF2008-0273). The Prague substudy was supported by research grants from the Ministry of Health of the Czech Republic and General University Hospital in Prague (IGA 10024-4 and MZOVFN2005).

Author information

Author notes

  1. J M Moreno-Navarrete and V Touskova: These authors contributed equally to the work.

Authors and Affiliations

  1. Department of Diabetes, Endocrinology and Nutrition, Institut d’Investigació Biomèdica de Girona, and CIBER Fisiopatologia Obesidad y Nutricion (CB06/03/010), Instituto de Salud Carlos III, Girona, Spain

    J M Moreno-Navarrete, M Sabater, F Ortega, M Serrano, G Pardo, N Pueyo, W Ricart & J M Fernández-Real

  2. Third Department of Medicine, General University Hospital and First School of Medicine, Charles University, Prague, Czech Republic

    V Touskova, M Mraz, J Drapalova, Z Lacinova & M Haluzik

  3. Department of Endocrinology, Metabolic Research Laboratory, Clínica Universidad de Navarra, CIBEROBN (CB06/03/1014), Instituto de Salud Carlos III (ISCIII), Pamplona, Spain

    V Catalán, J Gómez-Ambrosi & G Frühbeck

  4. Department of Pathology, Hospital of Girona ‘Dr Josep Trueta’, Girona, Spain

    M R Ortiz

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  1. J M Moreno-Navarrete
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Corresponding author

Correspondence to J M Fernández-Real.

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Moreno-Navarrete, J., Touskova, V., Sabater, M. et al. Liver, but not adipose tissue PEDF gene expression is associated with insulin resistance. Int J Obes 37, 1230–1237 (2013). https://doi.org/10.1038/ijo.2012.223

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