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Adipocyte and cell biology

Adipose tissue loss and lipodystrophy in xylosyltransferase II deficient mice

International Journal of Obesity volume 43, pages 1783–1794 (2019)Cite this article

Subjects

Abstract

Background/objectives

The cellular and extracellular matrix (ECM) interactions that regulate adipose tissue homeostasis are incompletely understood. Proteoglycans (PGs) and their sulfated glycosaminoglycans (GAGs) provide spatial and temporal signals for ECM organization and interactions with resident cells by impacting growth factor and cytokine activity. Therefore, PGs and their GAGs could be significant to adipose tissue homeostasis. The purpose of this study was to determine the role of ECM sulfated GAGs in adipose tissue homeostasis.

Methods

Adipose tissue and metabolic homeostasis in mice deficient in xylosyltransferase 2 (Xylt2−/−) were examined by histologic analyses, gene expression analyses, whole body fat composition measurements, and glucose tolerance test. Adipose tissue inflammation and adipocyte precursors were characterized by flow cytometry and in vitro culture of mesenchymal stem cells.

Results

Xylt2−/− mice have low body weight due to overall reductions in abdominal fat deposition. Histologically, the adipocytes are reduced in size and number in both gonadal and mesenteric fat depots of Xylt2−/− mice. In addition, these mice are glucose intolerant, insulin resistant, and have increased serum triglycerides as compared to Xylt2 + / + control mice. Furthermore, the adipose tissue niche has increased inflammatory cells and enrichment of proinflammatory factors IL6 and IL1β, and these mice also have a loss of adipose tissue vascular endothelial cells. Lastly, xylosyltransferease-2 (XylT2) deficient mesenchymal stem cells from gonadal adipose tissue and bone marrow exhibit impaired adipogenic differentiation in vitro.

Conclusions

Decreased GAGs due to the loss of the key GAG assembly enzyme XylT2 causes reduced steady state adipose tissue stores leading to a unique lipodystrophic model. Accumulation of an adipocytic precursor pool of cells is discovered indicating an interruption in differentiation. Therefore, adipose tissue GAGs are important in the homeostasis of adipose tissue by mediating control of adipose precursor development, tissue inflammation, and vascular development.

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Acknowledgements

This work was supported by funds from the Oklahoma Center for Adult Stem Cell Research, a program of TSET, NIH Center of Biomedical Research Excellence (COBRE), P20 GM103648, P20GM103441, P30GM114731, Oklahoma State University Research Activity funding. We also thank the COBRE Animal Models Core for assistance. We also thank Huan Song for expert technical assistance.

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Authors and Affiliations

  1. Department of Physiological Sciences, Oklahoma State University, Stillwater, OK, 74078, USA

    Pulavendran Sivasami, Nabin Poudel, Maria Cristina Munteanu, Pamela Lovern, Lin Liu & Myron E. Hinsdale

  2. Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA

    Joanna Hudson & Myron E. Hinsdale

  3. Aging and Metabolism Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, 73104, USA

    Tim Griffin

  4. Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA

    Tim Griffin

  5. Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA

    Tim Griffin

  6. Reynolds Oklahoma Center on Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA

    Tim Griffin

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Sivasami, P., Poudel, N., Munteanu, M.C. et al. Adipose tissue loss and lipodystrophy in xylosyltransferase II deficient mice. Int J Obes 43, 1783–1794 (2019). https://doi.org/10.1038/s41366-019-0324-1

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