Thrombospondin1 Deficiency Attenuates Obesity-Associated Microvascular Complications in ApoE-/- Mice

Authors

Hasiyeti Maimaitiyiming, University of KentuckyFollow
Kate Clemons, University of Kentucky
Qi Zhou, University of Kentucky
Heather Norman, University of KentuckyFollow
Shuxia Wang, University of KentuckyFollow

Abstract

Obesity is associated with insulin resistance and the increased development of vascular complications. Previously, we have demonstrated that thrombospondin1 (TSP1) regulates macrophage function and contributes to obesity associated inflammation and insulin resistance. However, the role of TSP1 in the development of obesity associated vascular complications is not clear. Therefore, in the current study, we investigated whether TSP1 deficiency protects mice from obesity associated micro as well as macro-vascular complications in ApoE-/- mice. In this study, male ApoE-/- mice and ApoE-/-TSP1-/- mice were fed with a low-fat (LF) or a high-fat (HF) diet for 16 weeks. We found that body weight and fat mass increased similarly between the ApoE-/-TSP1-/- mice and ApoE-/- mice under HF feeding conditions. However, as compared to obese ApoE-/- mice, obese ApoE-/-TSP1-/- mice had improved glucose tolerance, increased insulin sensitivity, and reduced systemic inflammation. Aortic atherosclerotic lesion formation was similar in these two groups of mice. In contrast, albuminuria was attenuated and kidney fibrosis was reduced in obese ApoE-/-TSP1-/- mice compared to obese ApoE-/- mice. The improved kidney function in obese ApoE-/-TSP1-/- mice was associated with decreased renal lipid accumulation. Together, these data suggest that TSP1 deficiency did not affect the development of obesity associated macro-vascular complication, but attenuated obesity associated micro-vascular complications.

Document Type

Article

Publication Date

3-24-2015

Notes/Citation Information

Published in PLOS One, v. 10, no. 3, article e0121403, p. 1-14.

© 2015 Maimaitiyiming et al.

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Digital Object Identifier (DOI)

http://dx.doi.org/10.1371/journal.pone.0121403

Funding Information

Support was provided by I01 BX001204 from Veterans Affairs (to S. Wang); National Institutes of Health grants R01 DK081555 and DK098176 (to S. Wang); National Institutes of Health Training Grant DK07778 (to H. Norman); and a Centers of Biomedical Research Excellence grant P20GM103527-06. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Repository Citation

Maimaitiyiming, Hasiyeti; Clemons, Kate; Zhou, Qi; Norman, Heather; and Wang, Shuxia, "Thrombospondin1 Deficiency Attenuates Obesity-Associated Microvascular Complications in ApoE-/- Mice" (2015). Pharmacology and Nutritional Sciences Faculty Publications. 31.
https://uknowledge.uky.edu/pharmacol_facpub/31