OBJECTIVE: Diabetes-induced dyslipidemia is seen in streptozotocin-induced diabetic rats. This is caused, in part, by elevated intestinal acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity. Because two ACAT isozymes (ACAT-1 and ACAT-2) were identified, in the present study we determined which ACAT isozyme was involved in the elevated intestinal ACAT activity in diabetic rats. METHODS AND RESULTS: We cloned a full-length cDNA of rat ACAT-2. Its overexpression in ACAT-deficient AC29 cells demonstrated that the ACAT activity is derived from the cloned cDNA, and a 45-kDa protein of rat ACAT-2 cross-reacts with an anti-human ACAT-2 antibody. The tissue distribution of rat ACAT-2 mRNA revealed its restricted expression to liver and small intestine. Immunohistochemical analyses using an anti-human ACAT-2 antibody demonstrated that ACAT-2 is localized in villus-crypt axis of rat small intestine. The intestinal ACAT activity in diabetic rats was significantly immunodepleted by an anti-ACAT-2 antibody but not by an anti-ACAT-1 antibody. Finally, intestinal ACAT-2 in diabetic rats significantly increased at both protein and mRNA levels as compared with that in control rats. CONCLUSIONS: Our data demonstrate that ACAT-2 isozyme is responsible for the increased intestinal ACAT activity of diabetic rats, suggesting an important role of ACAT-2 for dyslipidemia in diabetic patients. Diabetic rats exhibit dyslipidemia caused, in part, by elevated intestinal acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity. We determined which ACAT isozyme (ACAT-1 or ACAT-2) was involved in the elevated intestinal ACAT activity in diabetic rats. We demonstrated an important role of ACAT-2, implicating its involvement in dyslipidemia in diabetic patients.
OBJECTIVE:Diabetes-induced dyslipidemia is seen in streptozotocin-induced diabeticrats. This is caused, in part, by elevated intestinal acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity. Because two ACAT isozymes (ACAT-1 and ACAT-2) were identified, in the present study we determined which ACAT isozyme was involved in the elevated intestinal ACAT activity in diabeticrats. METHODS AND RESULTS: We cloned a full-length cDNA of ratACAT-2. Its overexpression in ACAT-deficient AC29 cells demonstrated that the ACAT activity is derived from the cloned cDNA, and a 45-kDa protein of ratACAT-2 cross-reacts with an anti-humanACAT-2 antibody. The tissue distribution of ratACAT-2 mRNA revealed its restricted expression to liver and small intestine. Immunohistochemical analyses using an anti-humanACAT-2 antibody demonstrated that ACAT-2 is localized in villus-crypt axis of rat small intestine. The intestinal ACAT activity in diabeticrats was significantly immunodepleted by an anti-ACAT-2 antibody but not by an anti-ACAT-1 antibody. Finally, intestinal ACAT-2 in diabeticrats significantly increased at both protein and mRNA levels as compared with that in control rats. CONCLUSIONS: Our data demonstrate that ACAT-2 isozyme is responsible for the increased intestinal ACAT activity of diabeticrats, suggesting an important role of ACAT-2 for dyslipidemia in diabeticpatients. Diabeticrats exhibit dyslipidemia caused, in part, by elevated intestinal acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity. We determined which ACAT isozyme (ACAT-1 or ACAT-2) was involved in the elevated intestinal ACAT activity in diabeticrats. We demonstrated an important role of ACAT-2, implicating its involvement in dyslipidemia in diabeticpatients.
Authors: Chang Xie 谢畅; Zhang-Sen Zhou 周章森; Na Li 李钠; Yan Bian 卞艳; Yong-Jian Wang 王永建; Li-Juan Wang 王丽娟; Bo-Liang Li 李伯良; Bao-Liang Song 宋保亮 Journal: J Lipid Res Date: 2012-07-17 Impact factor: 5.922
Authors: Michael J Keenan; Roy J Martin; Anne M Raggio; Kathleen L McCutcheon; Ian L Brown; Anne Birkett; Susan S Newman; Jihad Skaf; Maren Hegsted; Richard T Tulley; Eric Blair; June Zhou Journal: J Nutrigenet Nutrigenomics Date: 2012-04-20
Authors: Kylie Kavanagh; Matthew A Davis; Li Zhang; Martha D Wilson; Thomas C Register; Michael R Adams; Lawrence L Rudel; Janice D Wagner Journal: Arterioscler Thromb Vasc Biol Date: 2009-10 Impact factor: 8.311