title: Acyl-coenzyme A:cholesterol acyltransferase-2 (ACAT-2) is responsible for elevated intestinal ACAT activity in diabetic rats.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Medical Biochemistry, Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Hori
authors.forename: Maki
authors.initials: M
authors.lastname: Satoh
authors.forename: Kohichiro
authors.initials: K
authors.lastname: Furukawa
authors.forename: Yu-ichiro
authors.initials: Y
authors.lastname: Sakamoto
authors.forename: Hideki
authors.initials: H
authors.lastname: Hakamata
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Komohara
authors.forename: Motohiro
authors.initials: M
authors.lastname: Takeya
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Akira
authors.initials: A
authors.lastname: Miyazaki
authors.forename: Seikoh
authors.initials: S
authors.lastname: Horiuchi
mesh_terms: D000818:Animals; D001483:Base Sequence; D016466:CHO Cells / Q000201:enzymology; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000493:pharmacokinetics; D006224:Cricetinae; D003412:Cricetulus; D018076:DNA, Complementary; D048909:Diabetes Complications / Q000201:enzymology*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000201:enzymology*; D004790:Enzyme Induction; D006949:Hyperlipidemias / Q000201:enzymology* / Q000209:etiology; D007408:Intestinal Absorption; D007421:Intestine, Small / Q000201:enzymology*; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D008099:Liver / Q000201:enzymology; D008297:Male; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000502:physiology; D002785:Sterol O-Acyltransferase / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013311:Streptozocin; D014162:Transfection; D014280:Triglycerides / Q000097:blood; D000097587:Sterol O-Acyltransferase 2
chemical_list: D002784:Cholesterol; D002791:Cholesterol, Dietary; D018076:DNA, Complementary; D007527:Isoenzymes; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D002785:Sterol O-Acyltransferase; D013311:Streptozocin; D014280:Triglycerides; D000097587:Sterol O-Acyltransferase 2