Loss of small heterodimer partner protects against atherosclerosis in apolipoprotein E-deficient mice

Min Joo Kim; Kwan Jae Lee; Ji-Yeon Hwang; Hye Seung Lee; Sung Hee Chio; Soo Lim; Hak Chul Jang; Young Joo Park

doi:10.1507/endocrj.EJ13-0212

ORIGINALS

Loss of small heterodimer partner protects against atherosclerosis in apolipoprotein E-deficient mice

Min Joo Kim, Kwan Jae Lee, Ji-Yeon Hwang, Hye Seung Lee, Sung Hee Chio, Soo Lim, Hak Chul Jang, Young Joo Park

Author information

Min Joo Kim
Department of Internal Medicine, Seoul National University College of Medicine, Seoul 110-744, Republic of Korea
Department of Internal Medicine, Korea Cancer Center Hospital, Seoul 139-706, Republic of Korea
Kwan Jae Lee
Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam 463-707, Republic of Korea
Ji-Yeon Hwang
Preclinical Research Center, Biomedical Research Institute, Seoul National University Bundang Hospital, Seongnam 463-707, Republic of Korea
Hye Seung Lee
Department of Pathology, Seoul National University Bundang Hospital, Seongnam 463-707, Republic of Korea
Sung Hee Chio
Department of Internal Medicine, Seoul National University College of Medicine, Seoul 110-744, Republic of Korea
Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam 463-707, Republic of Korea
Soo Lim
Department of Internal Medicine, Seoul National University College of Medicine, Seoul 110-744, Republic of Korea
Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam 463-707, Republic of Korea
Hak Chul Jang
Department of Internal Medicine, Seoul National University College of Medicine, Seoul 110-744, Republic of Korea
Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam 463-707, Republic of Korea
Young Joo Park
Department of Internal Medicine, Seoul National University College of Medicine, Seoul 110-744, Republic of Korea

Keywords: Small heterodimer partner, Atherosclerosis, Obesity, Adipose tissue, Cholesterol 7-alpha-hydroxylase

JOURNAL FREE ACCESS

2013 Volume 60 Issue 10 Pages 1171-1177

DOI https://doi.org/10.1507/endocrj.EJ13-0212

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Abstract

Small heterodimer partner (SHP) is involved in bile, lipid, and glucose metabolism. The aim of this study was to investigate the effect of SHP on the development of atherosclerosis. Apolipoprotein E knockout (ApoE^-/-) mice were crossed with SHP knockout (SHP^-/-) mice to generate double knockout (ApoE^-/-SHP^-/-) mice. ApoE^-/- and ApoE^-/-SHP^-/- male mice were fed a western diet for 20 weeks. Body weight in ApoE^-/-SHP^-/- mice was significantly lower than that in ApoE^-/- mice (37 ± 1 g vs. 42 ± 1 g, p < 0.01). Loss of SHP in ApoE^-/- mice decreased the size of adipocytes in white adipose tissue and reduced lipid accumulation in the liver. Glucose intolerance was improved in ApoE^-/-SHP^-/- mice as compared with ApoE^-/- mice (p < 0.01). There was no statistical difference in non-high density lipoprotein cholesterol levels between ApoE^-/-SHP^-/- mice and ApoE^-/- mice despite an increase of cholesterol 7α-hydroxylase expression in the liver. The proportion of atherosclerotic lesions in the aorta was significantly lower in ApoE^-/-SHP^-/- mice than in ApoE^-/- mice (2.8 ± 2.0% vs. 9.1 ± 1.9%, p < 0.01). In conclusion, loss of SHP function can prevent atherosclerosis, and resistance to diet-induced obesity is the primary factor contributing to this protective effect.

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