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Apolipoprotein E2 Accentuates Postprandial Inflammation and Diet-Induced Obesity to Promote Hyperinsulinemia in Mice

Genetic studies have revealed the association between the ε2 allele of the apolipoprotein E (apoE) gene and greater risk of metabolic diseases. This study compared C57BL/6 mice in which the endogenous mouse gene has been replaced by the human APOE2 or APOE3 gene (APOE2 and APOE3 mice) to identify th...

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Autores principales: Kuhel, David G., Konaniah, Eddy S., Basford, Joshua E., McVey, Courtney, Goodin, Colleen T., Chatterjee, Tapan K., Weintraub, Neal L., Hui, David Y.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3554349/
https://www.ncbi.nlm.nih.gov/pubmed/22961083
http://dx.doi.org/10.2337/db12-0390
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author Kuhel, David G.
Konaniah, Eddy S.
Basford, Joshua E.
McVey, Courtney
Goodin, Colleen T.
Chatterjee, Tapan K.
Weintraub, Neal L.
Hui, David Y.
author_facet Kuhel, David G.
Konaniah, Eddy S.
Basford, Joshua E.
McVey, Courtney
Goodin, Colleen T.
Chatterjee, Tapan K.
Weintraub, Neal L.
Hui, David Y.
author_sort Kuhel, David G.
collection PubMed
description Genetic studies have revealed the association between the ε2 allele of the apolipoprotein E (apoE) gene and greater risk of metabolic diseases. This study compared C57BL/6 mice in which the endogenous mouse gene has been replaced by the human APOE2 or APOE3 gene (APOE2 and APOE3 mice) to identify the mechanism underlying the relationship between ε2 and obesity and diabetes. In comparison with APOE3 mice, the APOE2 mice had elevated fasting plasma lipid and insulin levels and displayed prolonged postprandial hyperlipidemia accompanied by increased granulocyte number and inflammation 2 h after being fed a lipid-rich meal. In comparison with APOE3 mice, the APOE2 mice also showed increased adiposity when maintained on a Western-type, high-fat, high-cholesterol diet. Adipose tissue dysfunction with increased macrophage infiltration, abundant crown-like structures, and inflammation were also observed in adipose tissues of APOE2 mice. The severe adipocyte dysfunction and tissue inflammation corresponded with the robust hyperinsulinemia observed in APOE2 mice after being fed the Western-type diet. Taken together, these data showed that impaired plasma clearance of apoE2-containing, triglyceride-rich lipoproteins promotes lipid redistribution to neutrophils and adipocytes to accentuate inflammation and adiposity, thereby accelerating the development of hyperinsulinemia that will ultimately lead to advanced metabolic diseases.
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spelling pubmed-35543492014-02-01 Apolipoprotein E2 Accentuates Postprandial Inflammation and Diet-Induced Obesity to Promote Hyperinsulinemia in Mice Kuhel, David G. Konaniah, Eddy S. Basford, Joshua E. McVey, Courtney Goodin, Colleen T. Chatterjee, Tapan K. Weintraub, Neal L. Hui, David Y. Diabetes Metabolism Genetic studies have revealed the association between the ε2 allele of the apolipoprotein E (apoE) gene and greater risk of metabolic diseases. This study compared C57BL/6 mice in which the endogenous mouse gene has been replaced by the human APOE2 or APOE3 gene (APOE2 and APOE3 mice) to identify the mechanism underlying the relationship between ε2 and obesity and diabetes. In comparison with APOE3 mice, the APOE2 mice had elevated fasting plasma lipid and insulin levels and displayed prolonged postprandial hyperlipidemia accompanied by increased granulocyte number and inflammation 2 h after being fed a lipid-rich meal. In comparison with APOE3 mice, the APOE2 mice also showed increased adiposity when maintained on a Western-type, high-fat, high-cholesterol diet. Adipose tissue dysfunction with increased macrophage infiltration, abundant crown-like structures, and inflammation were also observed in adipose tissues of APOE2 mice. The severe adipocyte dysfunction and tissue inflammation corresponded with the robust hyperinsulinemia observed in APOE2 mice after being fed the Western-type diet. Taken together, these data showed that impaired plasma clearance of apoE2-containing, triglyceride-rich lipoproteins promotes lipid redistribution to neutrophils and adipocytes to accentuate inflammation and adiposity, thereby accelerating the development of hyperinsulinemia that will ultimately lead to advanced metabolic diseases. American Diabetes Association 2013-02 2013-01-17 /pmc/articles/PMC3554349/ /pubmed/22961083 http://dx.doi.org/10.2337/db12-0390 Text en © 2013 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Metabolism
Kuhel, David G.
Konaniah, Eddy S.
Basford, Joshua E.
McVey, Courtney
Goodin, Colleen T.
Chatterjee, Tapan K.
Weintraub, Neal L.
Hui, David Y.
Apolipoprotein E2 Accentuates Postprandial Inflammation and Diet-Induced Obesity to Promote Hyperinsulinemia in Mice
title Apolipoprotein E2 Accentuates Postprandial Inflammation and Diet-Induced Obesity to Promote Hyperinsulinemia in Mice
title_full Apolipoprotein E2 Accentuates Postprandial Inflammation and Diet-Induced Obesity to Promote Hyperinsulinemia in Mice
title_fullStr Apolipoprotein E2 Accentuates Postprandial Inflammation and Diet-Induced Obesity to Promote Hyperinsulinemia in Mice
title_full_unstemmed Apolipoprotein E2 Accentuates Postprandial Inflammation and Diet-Induced Obesity to Promote Hyperinsulinemia in Mice
title_short Apolipoprotein E2 Accentuates Postprandial Inflammation and Diet-Induced Obesity to Promote Hyperinsulinemia in Mice
title_sort apolipoprotein e2 accentuates postprandial inflammation and diet-induced obesity to promote hyperinsulinemia in mice
topic Metabolism
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3554349/
https://www.ncbi.nlm.nih.gov/pubmed/22961083
http://dx.doi.org/10.2337/db12-0390
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