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Prevention of high-fat diet-induced adipose tissue remodeling in obese diabetic mice by n-3 polyunsaturated fatty acids

International Journal of Obesity volume 31, pages 1004–1013 (2007)Cite this article

Abstract

Objective:

Obesity is associated with reduced insulin sensitivity and extensive reorganization of adipose tissue. As polyunsaturated fatty acids (PUFA) appear to inhibit diabetes development, we investigated PUFA effects on markers of matrix remodeling in white adipose tissue.

Methods and procedure:

Male obese diabetic (db/db) mice were treated with either a low-fat standard diet (LF), or high-fat diets rich in saturated and monounsaturated fatty acids (HF/S), n-6 PUFA (HF/6) or the latter including marine n-3 PUFA (HF/3). White adipose tissue was analyzed for gene expression, fatty acid composition and by immunofluorescence.

Results:

HF/S treatment increased adipose tissue expression of a number of genes involved in matrix degradation including matrix metalloproteinase (MMP)-12, -14 and cathepsin K, L and S compared with LF. MMP-12 gene was expressed in macrophages and adipocytes, and MMP-12 protein colocalized with both cell types. In addition, mean adipocyte area increased by 1.6-fold in HF/S-treated mice. Genes essential for collagen production, such as procollagen I, III, VI, tenascin C and biglycan were upregulated in HF/S-treated animals as well. N-3 PUFA supplementation resulted in enrichment of these fatty acids in adipose tissue. Moreover, n-3 PUFA inhibited the HF/S-induced upregulation of genes involved in matrix degradation and production I restored mean adipocyte area and prevented MMP-12 expression in macrophages and adipocytes.

Conclusion:

N-3 PUFA prevent high-fat diet-induced matrix remodeling and adipocyte enlargement in adipose tissue of obese diabetic mice. Such changes could contribute to diabetes prevention by n-3 PUFA in obese patients.

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Acknowledgements

This work was supported by the Joseph-Skoda-Award of the Austrian Association of Internal Medicine to (TMS) and by CeMM – Center of Molecular Medicine, a basic research institute within the companies of the Austrian Academy of Sciences (to TMS and WW).

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Authors and Affiliations

  1. Clinical Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University Vienna, Vienna, Austria

    J Huber, M Löffler, J Todoric, M Zeyda, R Geyeregger, W Waldhäusl & T M Stulnig

  2. Department of Medical and Chemical Laboratory Diagnostics, Medical University Vienna and Ludwig Boltzmann Institute for Clinical and Experimental Oncology, Vienna, Austria

    M Bilban

  3. Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    M Reimers

  4. Department of Pharmacology, Cardiovascular Research Center, University of Virginia, Charlottesville, VA, USA

    A Kadl & N Leitinger

  5. Division of Food Chemistry, Department of Food Science and Technology, Boku University of Natural Resourses and Applied Life Sciences, Vienna, Austria

    M Schreiner

  6. Clinical Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University Vienna, Vienna, Austria

    T Weichhart

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Correspondence to T M Stulnig.

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Huber, J., Löffler, M., Bilban, M. et al. Prevention of high-fat diet-induced adipose tissue remodeling in obese diabetic mice by n-3 polyunsaturated fatty acids. Int J Obes 31, 1004–1013 (2007). https://doi.org/10.1038/sj.ijo.0803511

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