Apolipoprotein E2 accentuates postprandial inflammation and diet-induced obesity to promote hyperinsulinemia in mice

David G. Kuhel, Eddy S. Konaniah, Joshua E. Basford, Courtney McVey, Colleen T. Goodin, Tapan Kumar Chatterjee, Neal Lee Weintraub, David Y. Hui

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

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 This study compared C57BL/6 mice in which the endogenous mouse gene has been replaced by the human APOE2 or APOE3 gene (APOE2 and APOE3 mice) to identify the mechanism underlying the relationship between ε2 and obesity and diabetes.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 Westerntype 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.

Original languageEnglish (US)
Pages (from-to)382-391
Number of pages10
JournalDiabetes
Volume62
Issue number2
DOIs
StatePublished - Feb 1 2013

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Apolipoprotein E2
Hyperinsulinism
Obesity
Diet
Inflammation
Metabolic Diseases
Adiposity
Lipids
Adipocytes
Adipose Tissue
Genes
High Fat Diet
Hyperlipidemias
Crowns
Inbred C57BL Mouse
Granulocytes
Lipoproteins
Meals
Fasting
Triglycerides

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Kuhel, D. G., Konaniah, E. S., Basford, J. E., McVey, C., Goodin, C. T., Chatterjee, T. K., ... Hui, D. Y. (2013). Apolipoprotein E2 accentuates postprandial inflammation and diet-induced obesity to promote hyperinsulinemia in mice. Diabetes, 62(2), 382-391. https://doi.org/10.2337/db12-0390

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 Kumar; Weintraub, Neal Lee; Hui, David Y.

In: Diabetes, Vol. 62, No. 2, 01.02.2013, p. 382-391.

Research output: Contribution to journalArticle

Kuhel, DG, Konaniah, ES, Basford, JE, McVey, C, Goodin, CT, Chatterjee, TK, Weintraub, NL & Hui, DY 2013, 'Apolipoprotein E2 accentuates postprandial inflammation and diet-induced obesity to promote hyperinsulinemia in mice', Diabetes, vol. 62, no. 2, pp. 382-391. https://doi.org/10.2337/db12-0390
Kuhel DG, Konaniah ES, Basford JE, McVey C, Goodin CT, Chatterjee TK et al. Apolipoprotein E2 accentuates postprandial inflammation and diet-induced obesity to promote hyperinsulinemia in mice. Diabetes. 2013 Feb 1;62(2):382-391. https://doi.org/10.2337/db12-0390
Kuhel, David G. ; Konaniah, Eddy S. ; Basford, Joshua E. ; McVey, Courtney ; Goodin, Colleen T. ; Chatterjee, Tapan Kumar ; Weintraub, Neal Lee ; Hui, David Y. / Apolipoprotein E2 accentuates postprandial inflammation and diet-induced obesity to promote hyperinsulinemia in mice. In: Diabetes. 2013 ; Vol. 62, No. 2. pp. 382-391.
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