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Reversal of adipose tissue loss by probucol in mice with deficiency of both scavenger receptor class B type 1 and LDL receptor on high fat diet.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2018 Mar 11; Vol. 497 (3), pp. 930-936. Date of Electronic Publication: 2017 May 15. - Publication Year :
- 2018
-
Abstract
- Scavenger receptor class B type 1(SR-B1) and low density lipoprotein receptor (LDLR) play vital roles in cholesterol homeostasis. Previous studies indicated a strong link between cholesterol and adipose tissue (AT). In this study, adult male SR-B1 and LDLR double knockout (DKO) mice were fed with high fat diet (HFD) for 3 months. Interestingly, we found severe loss of AT in DKO mice fed with HFD. To reverse the AT loss in DKO mice, 1% probucol was added in HFD. In DKO mice on HFD, plasma total cholesterol (TC) and free cholesterol (FC) levels were increased 6 and 15 folds respectively compared with wild type (WT) mice. We found severe loss of AT in whole body of DKO mice compared with WT or single KO mice. In AT of DKO mice, histology showed the very small size of adipocytes and infiltration of inflammatory cells; Genes expressions related to fatty acid uptake, lipogenesis and adipogenesis were decreased; TUNEL analysis and related genes expressions of endoplasmic reticulum (ER) stress and inflammation were significantly higher than those of WT or single KO mice. Probucol could reduce increased TC and FC levels, and reverse the loss of fat and apoptosis of AT in DKO mice. AT loss in DKO mice with HFD was probably due to high levels of FC which led to apoptosis induced by ER stress and inflammation of AT. This study provided a novel utility of probucol in rescue of fat loss in DKO mice.<br /> (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Subjects :
- Adipose Tissue metabolism
Adipose Tissue pathology
Animals
Antioxidants pharmacology
Endoplasmic Reticulum Stress drug effects
Gene Knockout Techniques
Inflammation drug therapy
Inflammation genetics
Inflammation metabolism
Inflammation pathology
Mice, Inbred C57BL
Mice, Knockout
Receptors, LDL metabolism
Scavenger Receptors, Class B metabolism
Adipose Tissue drug effects
Anticholesteremic Agents pharmacology
Apoptosis drug effects
Diet, High-Fat adverse effects
Probucol pharmacology
Receptors, LDL genetics
Scavenger Receptors, Class B genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 497
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 28522295
- Full Text :
- https://doi.org/10.1016/j.bbrc.2017.05.017