Petäistö, T., Vicente, D., Mäkelä, K.A., Finnilä, M.A., Miinalainen, I., Koivunen, J., Izzi, V., Aikio, M., Karppinen, S.‐M., Devarajan, R., Thevenot, J., Herzig, K.‐H., Heljasvaara, R. and Pihlajaniemi, T. (2020), Lack of collagen XVIII leads to lipodystrophy and perturbs hepatic glucose and lipid homeostasis. J Physiol, 598: 3373-3393. doi:10.1113/JP279559
Lack of collagen XVIII leads to lipodystrophy and perturbs hepatic glucose and lipid homeostasis
|Author:||Petäistö, Tiina1; Vicente, David1; Mäkelä, Kari A.2;|
1Oulu Center for Cell‐Matrix Research, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland
2Research Unit of Biomedicine, Biocenter Oulu and Faculty of Medicine, University of Oulu, Oulu, Finland
3Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland
4Biocenter Oulu, University of Oulu, Oulu, Finland
5Department of Biomedicine, Centre for Cancer Biomarkers (CCBIO), University of Bergen, Bergen, Norway
|Online Access:||PDF Full Text (PDF, 8.9 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe2020062946196
John Wiley & Sons,
|Publish Date:|| 2020-06-29
Liver and adipose tissues play important roles in the regulation of systemic glucose and lipid metabolism. Extracellular matrix synthesis and remodelling are significantly altered in these tissues in obesity and type 2 diabetes. Collagen XVIII is a ubiquitous extracellular matrix component, and it occurs in three isoforms which differ in terms of molecular size, domain structure and tissue distribution. We recently showed that, in mice, the lack of collagen XVIII, and especially its medium and long isoforms, leads to reduced adiposity and dyslipidaemia. To address the metabolic consequences of these intriguing observations, we assessed whole‐body glucose homeostasis in mice challenged with a high‐fat diet and in normal physiological conditions. We observed that, in the high caloric diet, the overall adiposity was decreased by 30%, serum triglyceride values were threefold higher and the steatotic area in liver was twofold larger in collagen XVIII knockout mice compared with controls. We demonstrated that mice lacking either all three collagen XVIII isoforms, or specifically, the medium and long isoforms develop insulin resistance and glucose intolerance. Furthermore, we found that ablation of collagen XVIII leads to increased heat production in low temperatures and to reduction of the high blood triglyceride levels of the knockout mice to the level of wild‐type mice. Our data indicate that collagen XVIII plays a role in the regulation of glucose tolerance, insulin sensitivity and lipid homeostasis, principally through its ability to regulate the expansion of the adipose tissue. These findings advance the understanding of metabolic disorders.
Journal of physiology
|Pages:||3373 - 3393|
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
1182 Biochemistry, cell and molecular biology
This work was supported by grants from Biocenter Finland, Jane and Aatos Erkko Foundation, Academy of Finland (grant no. 294617 and 308867) and Sigrid Jusélius Foundation, and personal grants from the Scholarship Funds of the University of Oulu to D.V., the Kerttu Saalasti Foundation to T.Pe. and the Diabetes Research Foundation to M.A.
|Academy of Finland Grant Number:||
294617 (Academy of Finland Funding decision)
308867 (Academy of Finland Funding decision)
© 2020 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.