title: Hepatic carboxylesterase 1 is induced by glucose and regulates postprandial glucose levels.
abstract: Metabolic syndrome, characterized by obesity, hyperglycemia, dyslipidemia and hypertension, increases the risks for cardiovascular disease, diabetes and stroke. Carboxylesterase 1 (CES1) is an enzyme that hydrolyzes triglycerides and cholesterol esters, and is important for lipid metabolism. Our previous data show that over-expression of mouse hepatic CES1 lowers plasma glucose levels and improves insulin sensitivity in diabetic ob/ob mice. In the present study, we determined the physiological role of hepatic CES1 in glucose homeostasis. Hepatic CES1 expression was reduced by fasting but increased in diabetic mice. Treatment of mice with glucose induced hepatic CES1 expression. Consistent with the in vivo study, glucose stimulated CES1 promoter activity and increased acetylation of histone 3 and histone 4 in the CES1 chromatin. Knockdown of ATP-citrate lyase (ACL), an enzyme that regulates histone acetylation, abolished glucose-mediated histone acetylation in the CES1 chromatin and glucose-induced hepatic CES1 expression. Finally, knockdown of hepatic CES1 significantly increased postprandial blood glucose levels. In conclusion, the present study uncovers a novel glucose-CES1-glucose pathway which may play an important role in regulating postprandial blood glucose levels.
authors.affiliation: Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, Ohio, United States of America.
authors.forename: Jiesi
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, Ohio, United States of America.
authors.forename: Liya
authors.initials: L
authors.lastname: Yin
authors.affiliation: Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, Ohio, United States of America.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, Ohio, United States of America.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, Ohio, United States of America; Department of Pharmacology and Toxicology, College of Pharmacy, University of Baghdad, Baghdad, Iraq.
authors.forename: Munaf
authors.initials: M
authors.lastname: Zalzala
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Akron, Akron, Ohio, United States of America.
authors.forename: Gang
authors.initials: G
authors.lastname: Cheng
authors.affiliation: Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, Ohio, United States of America.
authors.forename: Yanqiao
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D001275:ATP Citrate (pro-S)-Lyase / Q000378:metabolism; D000107:Acetylation / Q000187:drug effects; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D006657:Histones / Q000378:metabolism; D006706:Homeostasis; D008099:Liver / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009752:Nutritional Status; D019518:Postprandial Period
chemical_list: D001786:Blood Glucose; D002843:Chromatin; D006657:Histones; D001275:ATP Citrate (pro-S)-Lyase; D002265:Carboxylic Ester Hydrolases; C545375:carboxylesterase 1, mouse; D005947:Glucose