Hepatic carboxylesterase 1 is induced by glucose and regulates postprandial glucose levels.
Male; Animals; Mice; Blood Glucose/*metabolism; Histones/metabolism; Gene Expression Regulation; Acetylation/drug effects; Glucose/*pharmacology; Homeostasis; Carboxylic Ester Hydrolases/*metabolism; Nutritional Status; *Postprandial Period; ATP Citrate (pro-S)-Lyase/metabolism; Chromatin/metabolism; Liver/*enzymology; Inbred C57BL; Enzymologic/drug effects
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.
Xu Jiesi; Yin Liya; Xu Yang; Li Yuanyuan; Zalzala Munaf; Cheng Gang; Zhang Yanqiao
PloS one
2014
2014
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1371/journal.pone.0109663" target="_blank" rel="noreferrer noopener">10.1371/journal.pone.0109663</a>
Sucrose, But Not Glucose, Blocks IL1-beta-Induced Inflammatory Response in Human Chondrocytes by Inducing Autophagy via AKT/mTOR Pathway.
*AUTOPHAGY; *CHONDROCYTES; *OSTEOARTHRITIS; *SUCROSE; Adult; Aged; Autophagy/*drug effects; Chondrocytes/*metabolism/pathology; Female; Glucose/*pharmacology; Humans; Inflammation/chemically induced/metabolism/pathology; Interleukin-1beta/*pharmacology; Male; Middle Aged; Osteoarthritis/*metabolism/pathology; Proto-Oncogene Proteins c-akt/*metabolism; Signal Transduction/*drug effects; Sucrose/*pharmacology; TOR Serine-Threonine Kinases/*metabolism
Pathogenesis of osteoarthritis (OA) is multifactorial but interleukin-1beta (IL-1beta) is known to be an important mediator of cartilage degradation. Autophagy is an essential cellular homeostasis mechanism and has been proposed to protect against cartilage degradation and chondrocyte death under pathological conditions. We investigated the role of autophagy activated by sucrose, a natural disaccharide, in suppressing inflammatory mediator's expression and cell death under pathological conditions in human chondrocytes. Autophagy activation was investigated by Western blotting for LC3 and Beclin-1, immunofluorescence staining for LC3 puncta, and measuring autophagic flux. Activation of mTOR, AKT, and P70S6K was evaluated by Western blotting. Chondrocyte apoptosis was evaluated by propidium iodide (PI) staining using flowcytometry, expression of Bax by Western blotting, gene expression by TaqMan assays and caspase 3/7 activity was measured using a luminescence-based assay. We found that sucrose-induced active autophagy in OA chondrocytes in vitro was dependent on the activation of AKT/mTOR/P70S6K signaling pathways but was independent of reactive oxygen species (ROS) production. Sucrose activated autophagy blocked IL-1beta-induced apoptosis and mRNA expression of MMP-13, COX-2, and IL-6 in human OA chondrocytes. Glucose or fructose, the two metabolites of sucrose, failed to induce autophagy indicating that autophagy was specifically mediated by sucrose. In conclusion, sucrose attenuated IL-1beta induced apoptosis and the expression of catabolic mediators by inducing autophagy, and the autophagy in part was mediated through the activation of AKT/mTOR/P70S6K signaling pathway in human OA chondrocytes. J. Cell. Biochem. 118: 629-639, 2017. (c) 2016 Wiley Periodicals, Inc.
Khan Nazir M; Ansari Mohammad Y; Haqqi Tariq M
Journal of cellular biochemistry
2017
2017-03
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1002/jcb.25750" target="_blank" rel="noreferrer noopener">10.1002/jcb.25750</a>