title: Loss of small heterodimer partner protects against atherosclerosis in apolipoprotein E-deficient mice.
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.
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul 110-744, Republic of Korea.
authors.forename: Min Joo
authors.initials: MJ
authors.lastname: Kim
authors.forename: Kwan Jae
authors.initials: KJ
authors.lastname: Lee
authors.forename: Ji-Yeon
authors.initials: JY
authors.lastname: Hwang
authors.forename: Hye Seung
authors.initials: HS
authors.lastname: Lee
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Chio
authors.forename: Soo
authors.initials: S
authors.lastname: Lim
authors.forename: Hak Chul
authors.initials: HC
authors.lastname: Jang
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Park
mesh_terms: D000818:Animals; D001011:Aorta / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000473:pathology / Q000517:prevention & control*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000096:biosynthesis; D004032:Diet / Q000009:adverse effects; D007333:Insulin Resistance; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000517:prevention & control; D018160:Receptors, Cytoplasmic and Nuclear / Q000172:deficiency*; D015430:Weight Gain / Q000187:drug effects
chemical_list: D001057:Apolipoproteins E; D018160:Receptors, Cytoplasmic and Nuclear; C099713:nuclear receptor subfamily 0, group B, member 2; D002790:Cholesterol 7-alpha-Hydroxylase