I Prostanoid Receptor–Mediated Inflammatory Pathway Promotes Hepatic Gluconeogenesis Through Activation of PKA and Inhibition of AKT

Yan, Shuai; Zhang, Qianqian; Zhong, Xiaojing; Tang, Juan; Wang, Yuanyang; Yu, Junjie; Zhou, Yi; Zhang, Jian; Guo, Feifan; Liu, Yi; FitzGerald, Garret A.; Yu, Ying

doi:10.2337/db13-1893

Cited by 24 publications

(30 citation statements)

References 48 publications

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“…Serum was separated and stored at −20°C for later use. Measurement of serum triglycerides (TG), total cholesterol, high‐density lipoprotein cholesterol (HDLC) and low‐density lipoprotein cholesterol (LDLC) levels was performed with commercial kits, following the manufacturer's protocol (BJKT, Beijing, China) (Yan et al ., ).…”

Section: Methodsmentioning

confidence: 97%

Aspirin enhances protective effect of fish oil against thrombosis and injury‐induced vascular remodelling

Gong

Lin

Piao

et al. 2015

British J Pharmacology

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Background and Purpose Although aspirin (acetylsalicylic acid) is commonly used to prevent ischaemic events in patients with coronary artery disease, many patients fail to respond to aspirin treatment. Dietary fish oil (FO), containing ω3 polyunsaturated fatty acids (PUFAs), has anti‐inflammatory and cardio‐protective properties, such as lowering cholesterol and modulating platelet activity. The objective of the present study was to investigate the potential additional effects of aspirin and FO on platelet activity and vascular response to injury. Experimental Approach Femoral arterial remodelling was induced by wire injury in mice. Platelet aggregation, and photochemical‐ and ferric chloride‐induced carotid artery thrombosis were employed to evaluate platelet function. Key Results FO treatment increased membrane ω3 PUFA incorporation, lowered plasma triglyceride and cholesterol levels, and reduced systolic BP in mice. FO or aspirin alone inhibited platelet aggregation; however, when combined, they exhibited synergistic suppression of platelet activity in mice, independent of COX‐1 inhibition. FO alone, but not aspirin, attenuated arterial neointimal growth in response to injury. Strikingly, a combination of FO and aspirin synergistically inhibited injury‐induced neointimal hyperplasia and reduced perivascular inflammatory reactions. Moreover, co‐administration of FO and aspirin decreased the expression of pro‐inflammatory cytokines and adhesion molecules in inflammatory cells. Consistently, a pro‐resolution lipid mediator‐Resolvin E1, was significantly elevated in plasma in FO/aspirin‐treated mice. Conclusions and Implications Co‐administration of FO and low‐dose aspirin may act synergistically to protect against thrombosis and injury‐induced vascular remodelling in mice. Our results support further investigation of adjuvant FO supplementation for patients with stable coronary artery disease. Linked Articles This article is part of a themed section on Chinese Innovation in Cardiovascular Drug Discovery. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-23

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Section: Methodsmentioning

confidence: 97%

Aspirin enhances protective effect of fish oil against thrombosis and injury‐induced vascular remodelling

Gong

Lin

Piao

et al. 2015

British J Pharmacology

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“…There was no significant change in the protein expression of known regulators of FAO, such as adipose triglyceride lipase, cluster of differentiation 36, fatty acid transport protein 1, or peroxisome proliferator-activated receptor α 20-23 ( Figure 3A). Similarly, there was no change in Akt phosphorylation at both Ser473 and Thr308 sites, p38 phosphorylation at Thr180, or protein kinase A phosphorylation at Thr197 (Figure 3B), which are proteins involved in glucose metabolism, [24][25][26] as well as in the regulation of FAO. 27,28 Despite the apparent lack of compensatory responses of important regulators of myocardial energy metabolism in ACC-DKI mice, there was a significant 3.6-fold increase of the uncoupling protein-3 (UCP3) in hearts of ACC-DKI mice compared with the hearts of WT ( Figure 3C).…”

Section: Loss Of Ampk-mediated Acc Phosphorylation In Hearts Of Acc-dmentioning

confidence: 99%

AMPK-Dependent Inhibitory Phosphorylation of ACC Is Not Essential for Maintaining Myocardial Fatty Acid Oxidation

Zordoky

Nagendran

Pulinilkunnil

et al. 2014

Circulation Research

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A cetyl coenzyme A carboxylase (ACC) plays an important role in regulating fatty acid oxidation (FAO) in the heart. 1,2 ACC catalyzes the conversion of acetyl CoA to malonyl-CoA. 3 In muscle, malonyl-CoA is an endogenous inhibitor of carnitine palmitoyl CoA transferase 1, which regulates long-chain fatty acyl CoA import into the mitochondria for β-oxidation. 4,5Two isoforms of ACC exist in the heart (ACC 1 and 2), 3,6 and both ACC1/2 can be regulated by inhibitory phosphorylation by AMP-activated protein kinase (AMPK).7 AMPK phosphorylates ACC1/2 on serine residues (Ser79/212), 7-9 leading to inhibition of ACC activity and decreased malonyl-CoA production.10 Despite the role that AMPK plays in regulating ACC activity and subsequent FAO, whether AMPK-mediated inactivation of ACC plays an obligate role in the maintenance of myocardial FAO rates has not been tested. In This Issue, see p 471To address this, we generated mutant mice with alanine knock-in mutations in both ACC1 (at Ser79) and ACC2 (at Ser212). In the liver and skeletal muscle, these mice maintain functional ACC and AMPK but express a mutant form of ACC that is no longer inhibited by AMPK phosphorylation. 11Consistent with the loss of AMPK-mediated inactivation of ACC, we have previously shown that these ACC-double knock-in (ACC-DKI) mice have significantly elevated ACC activity and impaired FAO in the liver.11 However, the effect of preventing AMPK-mediated phosphorylation of ACC in the heart has not been investigated. Herein, we show that hearts from ACC-DKI mice have increased malonyl-CoA levels compared with wild-type (WT) mice, but their FAO rates

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“…High‐fat diet boosts PG generation in mouse liver . In this study, all PG receptors were expressed at varying levels in liver, whereas only EP3 expression was up‐regulated in response to WD feeding in mice (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Plasma cholesterol (Chol) and triglyceride (TG) were evaluated using commercial kits according to the manufacturer's instructions (Wako Life Sciences, Richmond, VA). Hepatic Chol and TG contents were assessed following lipid extraction as described . Intracellular Chol levels were determined as described .…”

Section: Methodsmentioning

confidence: 99%

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Prostaglandin E2 promotes hepatic bile acid synthesis by an E prostanoid receptor 3‐mediated hepatocyte nuclear receptor 4α/cholesterol 7α‐hydroxylase pathway in mice

et al. 2016

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I Prostanoid Receptor–Mediated Inflammatory Pathway Promotes Hepatic Gluconeogenesis Through Activation of PKA and Inhibition of AKT

Cited by 24 publications

References 48 publications

Aspirin enhances protective effect of fish oil against thrombosis and injury‐induced vascular remodelling

Aspirin enhances protective effect of fish oil against thrombosis and injury‐induced vascular remodelling

AMPK-Dependent Inhibitory Phosphorylation of ACC Is Not Essential for Maintaining Myocardial Fatty Acid Oxidation

Prostaglandin E2 promotes hepatic bile acid synthesis by an E prostanoid receptor 3‐mediated hepatocyte nuclear receptor 4α/cholesterol 7α‐hydroxylase pathway in mice

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