CD36 deletion reduces VLDL secretion, modulates liver prostaglandins, and exacerbates hepatic steatosis in ob/ob mice[S]
Recent findings described the role of CD36-mediated signaling in regulating cellular calcium and the release of various bioactive molecules, including the prostaglandins, neurotransmitters, cholecystokinin, and secretin. Here we document the role of CD36 in the secretion of hepatic VLDL. CD36 deleti...
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doaj-646880587559491d8dd04b8ddd9099762021-04-28T05:59:06ZengElsevierJournal of Lipid Research0022-22752013-11-01541129882997CD36 deletion reduces VLDL secretion, modulates liver prostaglandins, and exacerbates hepatic steatosis in ob/ob mice[S]Fatiha Nassir0Okunade L. Adewole1Elizabeth M. Brunt2Nada A. Abumrad3To whom correspondence should be addressed; Department of Medicine Washington University School of Medicine, St. Louis, MO 63110Department of Medicine Washington University School of Medicine, St. Louis, MO 63110Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110Department of Medicine Washington University School of Medicine, St. Louis, MO 63110Recent findings described the role of CD36-mediated signaling in regulating cellular calcium and the release of various bioactive molecules, including the prostaglandins, neurotransmitters, cholecystokinin, and secretin. Here we document the role of CD36 in the secretion of hepatic VLDL. CD36 deletion resulted in 60% suppression of VLDL output in vivo, and VLDL secretion was reduced in vitro using incubated liver slices. The effect of CD36 deletion was mediated by enhancing formation of hepatic prostaglandins D2, F2, and E2. Treatment of CD36-deficient slices with inhibitors of cyclooxygenases reversed the reduction in triglyceride secretion. We also examined the effect of CD36 deletion on the obesity-associated spontaneous steatosis of the ob/ob mouse that is driven by enhanced de novo lipogenesis. Homozygous ob/ob mice lacking CD36 (ob-CD36−/−) were generated and studied for hepatic triglyceride accumulation and VLDL secretion. Livers of ob/ob mice were steatotic as expected and had 5-fold more CD36 on Kupffer cells and hepatocytes. CD36 deletion exacerbated the steatosis by impairing hepatic triglyceride and apoB secretion through increasing prostaglandin levels. These findings suggest an unappreciated role of CD36 in regulating VLDL secretion, which might have relevance to some forms of fatty liver. They provide insight into the association reported in humans between CD36 protein expression and serum levels of apoB and VLDL particle number.http://www.sciencedirect.com/science/article/pii/S0022227520350501triglycerideKupffer cellscyclooxygenase |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Fatiha Nassir Okunade L. Adewole Elizabeth M. Brunt Nada A. Abumrad |
spellingShingle |
Fatiha Nassir Okunade L. Adewole Elizabeth M. Brunt Nada A. Abumrad CD36 deletion reduces VLDL secretion, modulates liver prostaglandins, and exacerbates hepatic steatosis in ob/ob mice[S] Journal of Lipid Research triglyceride Kupffer cells cyclooxygenase |
author_facet |
Fatiha Nassir Okunade L. Adewole Elizabeth M. Brunt Nada A. Abumrad |
author_sort |
Fatiha Nassir |
title |
CD36 deletion reduces VLDL secretion, modulates liver prostaglandins, and exacerbates hepatic steatosis in ob/ob mice[S] |
title_short |
CD36 deletion reduces VLDL secretion, modulates liver prostaglandins, and exacerbates hepatic steatosis in ob/ob mice[S] |
title_full |
CD36 deletion reduces VLDL secretion, modulates liver prostaglandins, and exacerbates hepatic steatosis in ob/ob mice[S] |
title_fullStr |
CD36 deletion reduces VLDL secretion, modulates liver prostaglandins, and exacerbates hepatic steatosis in ob/ob mice[S] |
title_full_unstemmed |
CD36 deletion reduces VLDL secretion, modulates liver prostaglandins, and exacerbates hepatic steatosis in ob/ob mice[S] |
title_sort |
cd36 deletion reduces vldl secretion, modulates liver prostaglandins, and exacerbates hepatic steatosis in ob/ob mice[s] |
publisher |
Elsevier |
series |
Journal of Lipid Research |
issn |
0022-2275 |
publishDate |
2013-11-01 |
description |
Recent findings described the role of CD36-mediated signaling in regulating cellular calcium and the release of various bioactive molecules, including the prostaglandins, neurotransmitters, cholecystokinin, and secretin. Here we document the role of CD36 in the secretion of hepatic VLDL. CD36 deletion resulted in 60% suppression of VLDL output in vivo, and VLDL secretion was reduced in vitro using incubated liver slices. The effect of CD36 deletion was mediated by enhancing formation of hepatic prostaglandins D2, F2, and E2. Treatment of CD36-deficient slices with inhibitors of cyclooxygenases reversed the reduction in triglyceride secretion. We also examined the effect of CD36 deletion on the obesity-associated spontaneous steatosis of the ob/ob mouse that is driven by enhanced de novo lipogenesis. Homozygous ob/ob mice lacking CD36 (ob-CD36−/−) were generated and studied for hepatic triglyceride accumulation and VLDL secretion. Livers of ob/ob mice were steatotic as expected and had 5-fold more CD36 on Kupffer cells and hepatocytes. CD36 deletion exacerbated the steatosis by impairing hepatic triglyceride and apoB secretion through increasing prostaglandin levels. These findings suggest an unappreciated role of CD36 in regulating VLDL secretion, which might have relevance to some forms of fatty liver. They provide insight into the association reported in humans between CD36 protein expression and serum levels of apoB and VLDL particle number. |
topic |
triglyceride Kupffer cells cyclooxygenase |
url |
http://www.sciencedirect.com/science/article/pii/S0022227520350501 |
work_keys_str_mv |
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1721504714119446528 |