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.
Highlights
Metabolic syndrome refers to a group of metabolic disturbances, including obesity, hyperglycemia, dyslipidemia and hypertension, which increase the risks for cardiovascular disease, diabetes and stroke
To investigate whether hepatic Carboxylesterase 1 (CES1) expression is affected by a Western diet, we fed C57BL/6 mice a high fat/high cholesterol (HFHC) diet for 3 weeks; the data show that treatment with an High fat/high cholesterol (HFHC) diet for a short time did not regulate hepatic Ces1 expression (Figure 1E)
We investigated the effect of fasting on hepatic CES1 expression
Summary
Metabolic syndrome refers to a group of metabolic disturbances, including obesity, hyperglycemia, dyslipidemia and hypertension, which increase the risks for cardiovascular disease, diabetes and stroke. Lipid and glucose metabolism is tightly regulated in the body by modulating their dietary intake, transport, synthesis, storage and elimination. Any disturbances of these metabolic processes may increase the risks for metabolic diseases. Our recent data show that adenovirus-mediated over-expression of mouse CES1 (Ad-CES1) lowers hepatic TG and plasma glucose levels in both wild-type and diabetic mice and improves glucose tolerance in diabetic mice [5]. These latter data indicate that CES1 plays an important role in glucose metabolism
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
