Department of Internal Medicine, Seoul National University College of Medicine, Seoul 110-744, Republic of Korea.
Endocr J. 2013;60(10):1171-7. doi: 10.1507/endocrj.ej13-0212. Epub 2013 Aug 3.
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.
小异二聚体伴侣（SHP）参与胆汁、脂质和葡萄糖代谢。本研究旨在探讨 SHP 对动脉粥样硬化发展的影响。将载脂蛋白 E 基因敲除（ApoE-/-）小鼠与 SHP 基因敲除（SHP-/-）小鼠杂交，产生双重基因敲除（ApoE-/-SHP-/-）小鼠。雄性 ApoE-/-和 ApoE-/-SHP-/-小鼠喂食西方饮食 20 周。ApoE-/-SHP-/-小鼠的体重明显低于 ApoE-/-小鼠（37±1 g 比 42±1 g，p<0.01）。ApoE-/-小鼠中 SHP 的缺失减少了白色脂肪组织中脂肪细胞的大小，并减少了肝脏中的脂质积累。与 ApoE-/-小鼠相比，ApoE-/-SHP-/-小鼠的葡萄糖耐量得到改善（p<0.01）。尽管肝脏中胆固醇 7α-羟化酶的表达增加，但 ApoE-/-SHP-/-小鼠和 ApoE-/-小鼠之间的非高密度脂蛋白胆固醇水平没有统计学差异。ApoE-/-SHP-/-小鼠主动脉粥样硬化病变的比例明显低于 ApoE-/-小鼠（2.8±2.0%比 9.1±1.9%，p<0.01）。总之，SHP 功能缺失可预防动脉粥样硬化，而对饮食诱导肥胖的抵抗力是这种保护作用的主要因素。
