The Experts below are selected from a list of 1617 Experts worldwide ranked by ideXlab platform
Daniele Piomelli - One of the best experts on this subject based on the ideXlab platform.
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Mast Cell-Derived Histamine Regulates Liver Ketogenesis via Oleoylethanolamide Signaling.
Cell metabolism, 2018Co-Authors: Alessandra Misto, Maria Beatrice Passani, Gustavo Provensi, Valentina Vozella, Daniele PiomelliAbstract:Summary The conversion of lipolysis-derived fatty acids into ketone bodies (ketogenesis) is a crucial metabolic adaptation to prolonged periods of food scarcity. The process occurs primarily in liver mitochondria and is initiated by fatty-acid-mediated stimulation of the ligand-operated transcription factor, peroxisome proliferator-activated receptor-α ( PPAR -α). Here, we present evidence that mast cells contribute to the control of fasting-induced ketogenesis via a paracrine mechanism that involves secretion of histamine into the hepatic portal circulation, stimulation of liver H 1 receptors, and local biosynthesis of the high-affinity PPAR -α agonist, Oleoylethanolamide (OEA). Genetic or pharmacological interventions that disable any one of these events, including mast cell elimination, deletion of histamine- or OEA-synthesizing enzymes, and H 1 blockade, blunt ketogenesis without affecting lipolysis. The results reveal an unexpected role for mast cells in the regulation of systemic fatty-acid homeostasis, and suggest that OEA may act in concert with lipolysis-derived fatty acids to activate liver PPAR -α and promote ketogenesis.
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Dysfunctional Oleoylethanolamide signaling in a mouse model of Prader-Willi syndrome
Pharmacological research, 2016Co-Authors: Miki Igarashi, Fariba Oveisi, Vidya Narayanaswami, Virginia Kimonis, Pietro M. Galassetti, Kwang-mook Jung, Daniele PiomelliAbstract:Prader-Willi syndrome (PWS), the leading genetic cause of obesity, is characterized by a striking hyperphagic behavior that can lead to obesity, type-2 diabetes, cardiovascular disease and death. The molecular mechanism underlying impaired satiety in PWS is unknown. Oleoylethanolamide (OEA) is a lipid mediator involved in the control of feeding, body weight and energy metabolism. OEA produced by small-intestinal enterocytes during dietary fat digestion activates type-α peroxisome proliferator-activated receptors (PPAR-α) to trigger an afferent signal that causes satiety. Emerging evidence from genetic and human laboratory studies suggests that deficits in OEA-mediated signaling might be implicated in human obesity. In the present study, we investigated whether OEA contributes to feeding dysregulation in Magel2m+/p- (Magel2 KO) mice, an animal model of PWS. Fasted/refed male Magel2 KO mice eat more than do their wild-type littermates and become overweight with age. Meal pattern analyses show that hyperphagia in Magel2 KO is due to increased meal size and meal duration rather than to lengthening of the intermeal interval, which is suggestive of a defect in mechanisms underlying satiation. Food-dependent OEA accumulation in jejunum and fasting OEA levels in plasma are significantly greater in Magel2 KO mice than in wild-type controls. Together, these findings indicate that deletion of the Magel2 gene is accompanied by marked changes in OEA signaling. Importantly, intraperitoneal administration of OEA (10mg/kg) significantly reduces food intake in fasted/refed Magel2 KO mice, pointing to a possible use of this natural compound to control hunger in PWS.
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Role of Oleoylethanolamide as a feeding regulator in goldfish
Journal of Experimental Biology, 2014Co-Authors: Ana B. Tinoco, Daniele Piomelli, Andrea Armirotti, Esther Isorna, María Jesús Delgado, Nuria De PedroAbstract:Oleoylethanolamide (OEA) is a bioactive lipid mediator, produced in the intestine and other tissues, which is involved in energy balance regulation in mammals, modulating feeding and lipid metabolism. The purpose of the present study was to investigate the presence and possible role of OEA in feeding regulation in goldfish (Carassius auratus). We assessed whether goldfish peripheral tissues and brain contain OEA and their regulation by nutritional status. OEA was detected in all studied tissues (liver, intestinal bulb, proximal intestine, muscle, hypothalamus, telencephalon and brainstem). Food deprivation (48 h) reduced intestinal OEA levels and levels increased upon re-feeding, suggesting that this compound may be involved in the short-term regulation of food intake in goldfish, as a satiety factor. Next, the effects of acute intraperitoneal administration of OEA on feeding, swimming and plasma levels of glucose and triglycerides were analysed. Food intake, swimming activity and circulating triglyceride levels were reduced by OEA 2 h post-injection. Finally, the possible interplay among OEA and other feeding regulators (leptin, cholecystokinin, ghrelin, neuropeptide Y, orexin and monoamines) was investigated. OEA actions on energy homeostasis in goldfish could be mediated, at least in part, through interactions with ghrelin and the serotonergic system, as OEA treatment reduced ghrelin expression in the intestinal bulb, and increased serotonergic activity in the telencephalon. In summary, our results indicate for the first time in fish that OEA could be involved in the regulation of feeding, swimming and lipid metabolism, suggesting a high conservation of OEA actions in energy balance throughout vertebrate evolution.
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Sympathetic activity controls fat-induced Oleoylethanolamide signaling in small intestine.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011Co-Authors: Nicholas V. Dipatrizio, Gary J Schwartz, Silvana Gaetani, Giuseppe Astarita, Ana Guijarro, Daniele PiomelliAbstract:Ingestion of dietary fat stimulates production of the small-intestinal satiety factors Oleoylethanolamide (OEA) and N-palmitoyl-phosphatidylethanolamine (NPPE), which reduce food intake through a combination of local (OEA) and systemic (NPPE) actions. Previous studies have shown that sympathetic innervation of the gut is necessary for duodenal infusions of fat to induce satiety, suggesting that sympathetic activity may engage small-intestinal satiety signals such as OEA and NPPE. In the present study, we show that surgical resection of the sympathetic celiac-superior mesenteric ganglion complex, which sends projections to the upper gut, abolishes feeding-induced OEA production in rat small-intestinal cells. These effects are accounted for by suppression of OEA biosynthesis, and are mimicked by administration of the selective β2-adrenergic receptor antagonist ICI-118,551. We further show that sympathetic ganglionectomy or pharmacological blockade of β2-adrenergic receptors prevents NPPE release into the circulation. In addition, sympathetic ganglionectomy increases meal frequency and lowers satiety ratio, and these effects are corrected by pharmacological administration of OEA. The results suggest that sympathetic activity controls fat-induced satiety by enabling the coordinated production of local (OEA) and systemic (NPPE) satiety signals in the small intestine.
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CD36 gene deletion decreases Oleoylethanolamide levels in small intestine of free-feeding mice
Pharmacological research, 2009Co-Authors: Ana Guijarro, Giuseppe Astarita, Daniele PiomelliAbstract:Oleoylethanolamide (OEA) is an endogenous lipid mediator that decreases food intake and enhances lipid catabolism. Dietary fat stimulates OEA mobilization in the proximal small intestine, through a mechanism that requires the participation of the membrane glycoprotein CD36 (fatty acid translocase, FAT). CD36 is highly expressed in small-intestinal enterocytes and is involved in fatty acid uptake and intracellular signaling. Here, we analyze the impact of genetic CD36 deletion on OEA production in various mouse tissues under free-feeding conditions and at different times of the light/dark cycle. CD36 ablation decreases OEA levels in jejunum and plasma during the dark phase, when mice consume most of their daily food. CD36 deletion is also associated with reduced OEA levels in kidney, but not in other tissues including duodenum, stomach, adrenals, white and brown fat, heart, liver, pancreas, skeletal muscle and brain. The results underscore the important role of CD36 in jejunal OEA production linked to feeding.
Lichao Yang - One of the best experts on this subject based on the ideXlab platform.
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Oleoylethanolamide Increases Glycogen Synthesis and Inhibits Hepatic Gluconeogenesis via the LKB1/AMPK Pathway in Type 2 Diabetic Model.
The Journal of pharmacology and experimental therapeutics, 2020Co-Authors: Tong Ren, Lu Peng, Xin Jin, Rengong Zhuo, Huaying Zhang, Enhui Yao, Lichao YangAbstract:Oleoylethanolamide (OEA) is an endogenous peroxisome proliferator-activated receptor α (PPARα) agonist that acts on the peripheral control of energy metabolism. However, its therapeutic potential and related mechanisms in hepatic glucose metabolism under type 2 diabetes mellitus (T2DM) are not clear. Here, OEA treatment markedly improved glucose homeostasis in a PPARα-independent manner. OEA efficiently promoted glycogen synthesis and suppressed gluconeogenesis in mouse primary hepatocytes and liver tissue. OEA enhanced hepatic glycogen synthesis and inhibited gluconeogenesis via liver kinase B1 (LKB1)/5' AMP-activated protein kinase (AMPK) signaling pathways. PPARα was not involved in the roles of OEA in the LKB1/AMPK pathways. We found that OEA exerts its antidiabetic effect by increasing glycogenesis and decreasing gluconeogenesis via the LKB1/AMPK pathway. The ability of OEA to control hepatic LKB1/AMPK pathways may serve as a novel therapeutic approach for the treatment of T2DM. SIGNIFICANCE STATEMENT: Oleoylethanolamide (OEA) exerted a potent antihyperglycemic effect in a peroxisome proliferator-activated receptor α-independent manner. OEA played an antihyperglycemic role primarily via regulation of hepatic glycogen synthesis and gluconeogenesis. The main molecular mechanism of OEA in regulating liver glycometabolism is activating the liver kinase B1/5' AMP-activated protein kinase signaling pathways.
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Oleoylethanolamide increases glycogen synthesis and inhibits hepatic gluconeogenesis via the lkb1 ampk pathway in type 2 diabetic model
Journal of Pharmacology and Experimental Therapeutics, 2020Co-Authors: Tong Ren, Lu Peng, Xin Jin, Rengong Zhuo, Huaying Zhang, Enhui Yao, Lichao YangAbstract:Oleoylethanolamide (OEA) is an endogenous peroxisome proliferator-activated receptor α (PPARα) agonist that acts on the peripheral control of energy metabolism. However, its therapeutic potential and related mechanisms in hepatic glucose metabolism under type 2 diabetes mellitus (T2DM) are not clear. Here, OEA treatment markedly improved glucose homeostasis in a PPARα-independent manner. OEA efficiently promoted glycogen synthesis and suppressed gluconeogenesis in mouse primary hepatocytes and liver tissue. OEA enhanced hepatic glycogen synthesis and inhibited gluconeogenesis via liver kinase B1 (LKB1)/5' AMP-activated protein kinase (AMPK) signaling pathways. PPARα was not involved in the roles of OEA in the LKB1/AMPK pathways. We found that OEA exerts its antidiabetic effect by increasing glycogenesis and decreasing gluconeogenesis via the LKB1/AMPK pathway. The ability of OEA to control hepatic LKB1/AMPK pathways may serve as a novel therapeutic approach for the treatment of T2DM. SIGNIFICANCE STATEMENT: Oleoylethanolamide (OEA) exerted a potent antihyperglycemic effect in a peroxisome proliferator-activated receptor α-independent manner. OEA played an antihyperglycemic role primarily via regulation of hepatic glycogen synthesis and gluconeogenesis. The main molecular mechanism of OEA in regulating liver glycometabolism is activating the liver kinase B1/5' AMP-activated protein kinase signaling pathways.
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Immunomodulatory effect of Oleoylethanolamide in dendritic cells via TRPV1/AMPK activation.
Journal of cellular physiology, 2019Co-Authors: Enhui Yao, Lu Peng, Rui Huang, Jie Ren, Xuefeng Huang, Guixiang Zhang, Jinhua Huang, Xiazhen Yang, Xiaoxin Luo, Lichao YangAbstract:Oleoylethanolamide (OEA) is an endogenous lipid mediator involved in the control of feeding, body weight, and energy metabolism. However, whether OEA modulates maturation of dendritic cells (DCs) has never been addressed. Hence, we evaluated the effect of OEA on DCs maturation in bone marrow-derived DCs (BMDCs) in four aspects: (a) Cell surface markers were determined using flow cytometric analysis; (b) cell mobile ability was testified with the transwell assay; (c) stimulation of T cells proliferation was performed in a coculture system; and (d) cytokine production was measured using polymerase chain reaction (PCR). The result showed that, in mature BMDCs induced by lipopolysaccharides (LPS), the OEA treatment decreased expressions of cell surface markers, reduced cell migration, diminished the proliferation of cocultured T cells, and regulated cytokine production of BMDCs, indicating the modulatory effect of OEA on DCs maturation. Furthermore, to explore the underlying mechanism of the immunomodulatory effect of OEA, we used antagonists of transient receptor potential vanilloid-1 (TRPV1) and AMP-activated protein kinase (AMPK), determined the protein expressions of TRPV1/AMPK and Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) using western blot, and measured the intracellular calcium concentration using calcium imaging. The result illustrated that OEA downregulated TLR4/NF-κB, the classical pathway leading to DCs maturation induced by LPS, through the activation of TRPV1 and AMPK. Collectively, the present study suggests that OEA suppresses DCs maturation through the activation of TRPV1/AMPK. These findings increase our understanding of this endogenous lipid OEA.
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Oleoylethanolamide alleviates macrophage formation via AMPK/PPARα/STAT3 pathway.
Pharmacological reports : PR, 2018Co-Authors: Yun Zhao, Lu Peng, Lichao Yang, Jie Ren, Lu Yan, Xuefeng Huang, Guixiang Zhang, Bingqqian Chen, Yu Zhou, Li PengAbstract:Abstract Background Atherosclerosis is the main underlying cause of most cardiovascular diseases, and monocyte migrating to the vascular wall and subsequently differentiating into macrophage are critical steps in the process of atherosclerosis. The goal of this study was to clarify the effect of Oleoylethanolamide (OEA) on monocyte migration and subsequent macrophage formation in the vascular wall. Methods We studied OEA in two monocyte-migrating systems in vitro: one was a single cell system whereby monocytes were exposed to OEA directly; the other was a co-culture system whereby monocytes were exposed to OEA-treated macrophages. The effect of OEA on macrophage content in the vascular wall in vivo was measured in apolipoprotein E (apoE)−/− mice by CD68 immunohistochemistry. The protein and mRNA expressions with OEA treatment were examined using western blot and real-time PCR. Results Interestingly, OEA possessed dual-directional regulation of monocyte chemotaxis in vitro, with a stimulatory effect in the single cell system and a suppressive effect in the co-culture system. And OEA restrained macrophage deposition in the vascular wall of apoE−/− mice. The underlying mechanism of OEA suppressing monocyte migration in the co-culture system was that OEA increased phosphorylation of AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor α (PPARα) level, and decreased phosphorylation of signal transducer and activator of transcription 3 (STAT3) and monocyte chemoattractant protein-1 (MCP-1) level in macrophages, which was reinforced by the in vivo experiment. Conclusions OEA restrains excessive macrophage formation in the progressive lesion by inhibiting MCP-1 production of the existent macrophages through the AMPK/PPARα/STAT3 pathway.
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Oleoylethanolamide alleviates macrophage formation via ampk pparα stat3 pathway
Pharmacological Reports, 2018Co-Authors: Yun Zhao, Lu Peng, Lichao Yang, Jie Ren, Lu Yan, Xuefeng Huang, Guixiang Zhang, Bingqqian Chen, Yu Zhou, Li PengAbstract:Abstract Background Atherosclerosis is the main underlying cause of most cardiovascular diseases, and monocyte migrating to the vascular wall and subsequently differentiating into macrophage are critical steps in the process of atherosclerosis. The goal of this study was to clarify the effect of Oleoylethanolamide (OEA) on monocyte migration and subsequent macrophage formation in the vascular wall. Methods We studied OEA in two monocyte-migrating systems in vitro: one was a single cell system whereby monocytes were exposed to OEA directly; the other was a co-culture system whereby monocytes were exposed to OEA-treated macrophages. The effect of OEA on macrophage content in the vascular wall in vivo was measured in apolipoprotein E (apoE)−/− mice by CD68 immunohistochemistry. The protein and mRNA expressions with OEA treatment were examined using western blot and real-time PCR. Results Interestingly, OEA possessed dual-directional regulation of monocyte chemotaxis in vitro, with a stimulatory effect in the single cell system and a suppressive effect in the co-culture system. And OEA restrained macrophage deposition in the vascular wall of apoE−/− mice. The underlying mechanism of OEA suppressing monocyte migration in the co-culture system was that OEA increased phosphorylation of AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor α (PPARα) level, and decreased phosphorylation of signal transducer and activator of transcription 3 (STAT3) and monocyte chemoattractant protein-1 (MCP-1) level in macrophages, which was reinforced by the in vivo experiment. Conclusions OEA restrains excessive macrophage formation in the progressive lesion by inhibiting MCP-1 production of the existent macrophages through the AMPK/PPARα/STAT3 pathway.
Giuseppe Astarita - One of the best experts on this subject based on the ideXlab platform.
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Sympathetic activity controls fat-induced Oleoylethanolamide signaling in small intestine.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011Co-Authors: Nicholas V. Dipatrizio, Gary J Schwartz, Silvana Gaetani, Giuseppe Astarita, Ana Guijarro, Daniele PiomelliAbstract:Ingestion of dietary fat stimulates production of the small-intestinal satiety factors Oleoylethanolamide (OEA) and N-palmitoyl-phosphatidylethanolamine (NPPE), which reduce food intake through a combination of local (OEA) and systemic (NPPE) actions. Previous studies have shown that sympathetic innervation of the gut is necessary for duodenal infusions of fat to induce satiety, suggesting that sympathetic activity may engage small-intestinal satiety signals such as OEA and NPPE. In the present study, we show that surgical resection of the sympathetic celiac-superior mesenteric ganglion complex, which sends projections to the upper gut, abolishes feeding-induced OEA production in rat small-intestinal cells. These effects are accounted for by suppression of OEA biosynthesis, and are mimicked by administration of the selective β2-adrenergic receptor antagonist ICI-118,551. We further show that sympathetic ganglionectomy or pharmacological blockade of β2-adrenergic receptors prevents NPPE release into the circulation. In addition, sympathetic ganglionectomy increases meal frequency and lowers satiety ratio, and these effects are corrected by pharmacological administration of OEA. The results suggest that sympathetic activity controls fat-induced satiety by enabling the coordinated production of local (OEA) and systemic (NPPE) satiety signals in the small intestine.
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CD36 gene deletion decreases Oleoylethanolamide levels in small intestine of free-feeding mice
Pharmacological research, 2009Co-Authors: Ana Guijarro, Giuseppe Astarita, Daniele PiomelliAbstract:Oleoylethanolamide (OEA) is an endogenous lipid mediator that decreases food intake and enhances lipid catabolism. Dietary fat stimulates OEA mobilization in the proximal small intestine, through a mechanism that requires the participation of the membrane glycoprotein CD36 (fatty acid translocase, FAT). CD36 is highly expressed in small-intestinal enterocytes and is involved in fatty acid uptake and intracellular signaling. Here, we analyze the impact of genetic CD36 deletion on OEA production in various mouse tissues under free-feeding conditions and at different times of the light/dark cycle. CD36 ablation decreases OEA levels in jejunum and plasma during the dark phase, when mice consume most of their daily food. CD36 deletion is also associated with reduced OEA levels in kidney, but not in other tissues including duodenum, stomach, adrenals, white and brown fat, heart, liver, pancreas, skeletal muscle and brain. The results underscore the important role of CD36 in jejunal OEA production linked to feeding.
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Fat-induced satiety factor Oleoylethanolamide enhances memory consolidation
Proceedings of the National Academy of Sciences of the United States of America, 2009Co-Authors: Patrizia Campolongo, Giuseppe Astarita, Benno Roozendaal, Viviana Trezza, Vincenzo Cuomo, James L. Mcgaugh, Daniele PiomelliAbstract:The ability to remember contexts associated with aversive and rewarding experiences provides a clear adaptive advantage to animals foraging in the wild. The present experiments investigated whether hormonal signals released during feeding might enhance memory of recently experienced contextual information. Oleoylethanolamide (OEA) is an endogenous lipid mediator that is released when dietary fat enters the small intestine. OEA mediates fat-induced satiety by engaging type-alpha peroxisome proliferator-activated receptors (PPAR-alpha) in the gut and recruiting local afferents of the vagus nerve. Here we show that post-training administration of OEA in rats improves retention in the inhibitory avoidance and Morris water maze tasks. These effects are blocked by infusions of lidocaine into the nucleus tractus solitarii (NTS) and by propranolol infused into the basolateral complex of the amygdala (BLA). These findings suggest that the memory-enhancing signal generated by OEA activates the brain via afferent autonomic fibers and stimulates noradrenergic transmission in the BLA. The actions of OEA are mimicked by PPAR-alpha agonists and abolished in mutant mice lacking PPAR-alpha. The results indicate that OEA, acting as a PPAR-alpha agonist, facilitates memory consolidation through noradrenergic activation of the BLA, a mechanism that is also critically involved in memory enhancement induced by emotional arousal.
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the lipid messenger oea links dietary fat intake to satiety
Cell Metabolism, 2008Co-Authors: Gary J Schwartz, Daniele Piomelli, Silvana Gaetani, Giuseppe Astarita, Patrizia Campolongo, Vincenzo CuomoAbstract:The association between fat consumption and obesity underscores the need to identify physiological signals that control fat intake. Previous studies have shown that feeding stimulates small-intestinal mucosal cells to produce the lipid messenger Oleoylethanolamide (OEA) which, when administered as a drug, decreases meal frequency by engaging peroxisome proliferator-activated receptors-alpha (PPAR-alpha). Here, we report that duodenal infusion of fat stimulates OEA mobilization in the proximal small intestine, whereas infusion of protein or carbohydrate does not. OEA production utilizes dietary oleic acid as a substrate and is disrupted in mutant mice lacking the membrane fatty-acid transporter CD36. Targeted disruption of CD36 or PPAR-alpha abrogates the satiety response induced by fat. The results suggest that activation of small-intestinal OEA mobilization, enabled by CD36-mediated uptake of dietary oleic acid, serves as a molecular sensor linking fat ingestion to satiety.
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Targeted enhancement of Oleoylethanolamide production in proximal small intestine induces across-meal satiety in rats
American journal of physiology. Regulatory integrative and comparative physiology, 2008Co-Authors: Janet H. Kim, Fariba Oveisi, Giuseppe Astarita, Daniele PiomelliAbstract:Pharmacological administration of the natural lipid amide, Oleoylethanolamide (OEA), inhibits food intake in free-feeding rodents by prolonging latency to feed and postmeal interval. This anorexic ...
Lu Peng - One of the best experts on this subject based on the ideXlab platform.
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Oleoylethanolamide Increases Glycogen Synthesis and Inhibits Hepatic Gluconeogenesis via the LKB1/AMPK Pathway in Type 2 Diabetic Model.
The Journal of pharmacology and experimental therapeutics, 2020Co-Authors: Tong Ren, Lu Peng, Xin Jin, Rengong Zhuo, Huaying Zhang, Enhui Yao, Lichao YangAbstract:Oleoylethanolamide (OEA) is an endogenous peroxisome proliferator-activated receptor α (PPARα) agonist that acts on the peripheral control of energy metabolism. However, its therapeutic potential and related mechanisms in hepatic glucose metabolism under type 2 diabetes mellitus (T2DM) are not clear. Here, OEA treatment markedly improved glucose homeostasis in a PPARα-independent manner. OEA efficiently promoted glycogen synthesis and suppressed gluconeogenesis in mouse primary hepatocytes and liver tissue. OEA enhanced hepatic glycogen synthesis and inhibited gluconeogenesis via liver kinase B1 (LKB1)/5' AMP-activated protein kinase (AMPK) signaling pathways. PPARα was not involved in the roles of OEA in the LKB1/AMPK pathways. We found that OEA exerts its antidiabetic effect by increasing glycogenesis and decreasing gluconeogenesis via the LKB1/AMPK pathway. The ability of OEA to control hepatic LKB1/AMPK pathways may serve as a novel therapeutic approach for the treatment of T2DM. SIGNIFICANCE STATEMENT: Oleoylethanolamide (OEA) exerted a potent antihyperglycemic effect in a peroxisome proliferator-activated receptor α-independent manner. OEA played an antihyperglycemic role primarily via regulation of hepatic glycogen synthesis and gluconeogenesis. The main molecular mechanism of OEA in regulating liver glycometabolism is activating the liver kinase B1/5' AMP-activated protein kinase signaling pathways.
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Oleoylethanolamide increases glycogen synthesis and inhibits hepatic gluconeogenesis via the lkb1 ampk pathway in type 2 diabetic model
Journal of Pharmacology and Experimental Therapeutics, 2020Co-Authors: Tong Ren, Lu Peng, Xin Jin, Rengong Zhuo, Huaying Zhang, Enhui Yao, Lichao YangAbstract:Oleoylethanolamide (OEA) is an endogenous peroxisome proliferator-activated receptor α (PPARα) agonist that acts on the peripheral control of energy metabolism. However, its therapeutic potential and related mechanisms in hepatic glucose metabolism under type 2 diabetes mellitus (T2DM) are not clear. Here, OEA treatment markedly improved glucose homeostasis in a PPARα-independent manner. OEA efficiently promoted glycogen synthesis and suppressed gluconeogenesis in mouse primary hepatocytes and liver tissue. OEA enhanced hepatic glycogen synthesis and inhibited gluconeogenesis via liver kinase B1 (LKB1)/5' AMP-activated protein kinase (AMPK) signaling pathways. PPARα was not involved in the roles of OEA in the LKB1/AMPK pathways. We found that OEA exerts its antidiabetic effect by increasing glycogenesis and decreasing gluconeogenesis via the LKB1/AMPK pathway. The ability of OEA to control hepatic LKB1/AMPK pathways may serve as a novel therapeutic approach for the treatment of T2DM. SIGNIFICANCE STATEMENT: Oleoylethanolamide (OEA) exerted a potent antihyperglycemic effect in a peroxisome proliferator-activated receptor α-independent manner. OEA played an antihyperglycemic role primarily via regulation of hepatic glycogen synthesis and gluconeogenesis. The main molecular mechanism of OEA in regulating liver glycometabolism is activating the liver kinase B1/5' AMP-activated protein kinase signaling pathways.
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immunomodulatory effect of Oleoylethanolamide in dendritic cells via trpv1 ampk activation
Journal of Cellular Physiology, 2019Co-Authors: Lu Peng, Enhui Yao, Guixiang Zhang, Jinhua Huang, Xiazhen Yang, Xuefeng HuangAbstract:Oleoylethanolamide (OEA) is an endogenous lipid mediator involved in the control of feeding, body weight, and energy metabolism. However, whether OEA modulates maturation of dendritic cells (DCs) has never been addressed. Hence, we evaluated the effect of OEA on DCs maturation in bone marrow-derived DCs (BMDCs) in four aspects: (a) Cell surface markers were determined using flow cytometric analysis; (b) cell mobile ability was testified with the transwell assay; (c) stimulation of T cells proliferation was performed in a coculture system; and (d) cytokine production was measured using polymerase chain reaction (PCR). The result showed that, in mature BMDCs induced by lipopolysaccharides (LPS), the OEA treatment decreased expressions of cell surface markers, reduced cell migration, diminished the proliferation of cocultured T cells, and regulated cytokine production of BMDCs, indicating the modulatory effect of OEA on DCs maturation. Furthermore, to explore the underlying mechanism of the immunomodulatory effect of OEA, we used antagonists of transient receptor potential vanilloid-1 (TRPV1) and AMP-activated protein kinase (AMPK), determined the protein expressions of TRPV1/AMPK and Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) using western blot, and measured the intracellular calcium concentration using calcium imaging. The result illustrated that OEA downregulated TLR4/NF-κB, the classical pathway leading to DCs maturation induced by LPS, through the activation of TRPV1 and AMPK. Collectively, the present study suggests that OEA suppresses DCs maturation through the activation of TRPV1/AMPK. These findings increase our understanding of this endogenous lipid OEA.
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Immunomodulatory effect of Oleoylethanolamide in dendritic cells via TRPV1/AMPK activation.
Journal of cellular physiology, 2019Co-Authors: Enhui Yao, Lu Peng, Rui Huang, Jie Ren, Xuefeng Huang, Guixiang Zhang, Jinhua Huang, Xiazhen Yang, Xiaoxin Luo, Lichao YangAbstract:Oleoylethanolamide (OEA) is an endogenous lipid mediator involved in the control of feeding, body weight, and energy metabolism. However, whether OEA modulates maturation of dendritic cells (DCs) has never been addressed. Hence, we evaluated the effect of OEA on DCs maturation in bone marrow-derived DCs (BMDCs) in four aspects: (a) Cell surface markers were determined using flow cytometric analysis; (b) cell mobile ability was testified with the transwell assay; (c) stimulation of T cells proliferation was performed in a coculture system; and (d) cytokine production was measured using polymerase chain reaction (PCR). The result showed that, in mature BMDCs induced by lipopolysaccharides (LPS), the OEA treatment decreased expressions of cell surface markers, reduced cell migration, diminished the proliferation of cocultured T cells, and regulated cytokine production of BMDCs, indicating the modulatory effect of OEA on DCs maturation. Furthermore, to explore the underlying mechanism of the immunomodulatory effect of OEA, we used antagonists of transient receptor potential vanilloid-1 (TRPV1) and AMP-activated protein kinase (AMPK), determined the protein expressions of TRPV1/AMPK and Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) using western blot, and measured the intracellular calcium concentration using calcium imaging. The result illustrated that OEA downregulated TLR4/NF-κB, the classical pathway leading to DCs maturation induced by LPS, through the activation of TRPV1 and AMPK. Collectively, the present study suggests that OEA suppresses DCs maturation through the activation of TRPV1/AMPK. These findings increase our understanding of this endogenous lipid OEA.
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Oleoylethanolamide alleviates macrophage formation via AMPK/PPARα/STAT3 pathway.
Pharmacological reports : PR, 2018Co-Authors: Yun Zhao, Lu Peng, Lichao Yang, Jie Ren, Lu Yan, Xuefeng Huang, Guixiang Zhang, Bingqqian Chen, Yu Zhou, Li PengAbstract:Abstract Background Atherosclerosis is the main underlying cause of most cardiovascular diseases, and monocyte migrating to the vascular wall and subsequently differentiating into macrophage are critical steps in the process of atherosclerosis. The goal of this study was to clarify the effect of Oleoylethanolamide (OEA) on monocyte migration and subsequent macrophage formation in the vascular wall. Methods We studied OEA in two monocyte-migrating systems in vitro: one was a single cell system whereby monocytes were exposed to OEA directly; the other was a co-culture system whereby monocytes were exposed to OEA-treated macrophages. The effect of OEA on macrophage content in the vascular wall in vivo was measured in apolipoprotein E (apoE)−/− mice by CD68 immunohistochemistry. The protein and mRNA expressions with OEA treatment were examined using western blot and real-time PCR. Results Interestingly, OEA possessed dual-directional regulation of monocyte chemotaxis in vitro, with a stimulatory effect in the single cell system and a suppressive effect in the co-culture system. And OEA restrained macrophage deposition in the vascular wall of apoE−/− mice. The underlying mechanism of OEA suppressing monocyte migration in the co-culture system was that OEA increased phosphorylation of AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor α (PPARα) level, and decreased phosphorylation of signal transducer and activator of transcription 3 (STAT3) and monocyte chemoattractant protein-1 (MCP-1) level in macrophages, which was reinforced by the in vivo experiment. Conclusions OEA restrains excessive macrophage formation in the progressive lesion by inhibiting MCP-1 production of the existent macrophages through the AMPK/PPARα/STAT3 pathway.
Silvana Gaetani - One of the best experts on this subject based on the ideXlab platform.
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Vagal afferents are not necessary for the satiety effect of the gut lipid messenger Oleoylethanolamide.
American journal of physiology. Regulatory integrative and comparative physiology, 2014Co-Authors: Elnaz Karimian Azari, Deepti Ramachandran, Sandra Weibel, Myrtha Arnold, Adele Romano, Silvana Gaetani, Wolfgang Langhans, Abdelhak MansouriAbstract:The endogenous lipid messenger Oleoylethanolamide (OEA) inhibits eating and modulates fat metabolism supposedly through the activation of peroxisome proliferator-activated receptor-α (PPARα) and va...
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The satiety signal Oleoylethanolamide stimulates oxytocin neurosecretion from rat hypothalamic neurons
Peptides, 2013Co-Authors: Adele Romano, Pasqua Dipasquale, Silvia Cianci, Vincenzo Cuomo, Tommaso Cassano, Bianca Tempesta, Roberto Coccurello, Silvana GaetaniAbstract:The anandamide monounsaturated analogue Oleoylethanolamide (OEA) acts as satiety signal released from enterocytes upon the ingestion of dietary fats to prolong the interval to the next meal. This effect, which requires intact vagal fibers and intestinal PPAR-alpha receptors, is coupled to the increase of c-fos and oxytocin mRNA expression in neurons of the paraventricular nucleus (PVN) and is prevented by the intracerebroventricular administration of a selective oxytocin antagonist, thus suggesting a necessary role of oxytocinergic neurotransmission in the pro-satiety effect of OEA. By brain microdialysis and immunohistochemistry, in this study we demonstrate that OEA treatment can stimulate oxytocin neurosecretion from the PVN and enhance oxytocin expression at both axonal and somatodendritic levels of hypothalamic neurons. Such effects, which are maximum 2h after OEA administration, support the hypothesis that the satiety-inducing action of OEA is mediated by the activation of oxytocin hypothalamic neurons.
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Sympathetic activity controls fat-induced Oleoylethanolamide signaling in small intestine.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011Co-Authors: Nicholas V. Dipatrizio, Gary J Schwartz, Silvana Gaetani, Giuseppe Astarita, Ana Guijarro, Daniele PiomelliAbstract:Ingestion of dietary fat stimulates production of the small-intestinal satiety factors Oleoylethanolamide (OEA) and N-palmitoyl-phosphatidylethanolamine (NPPE), which reduce food intake through a combination of local (OEA) and systemic (NPPE) actions. Previous studies have shown that sympathetic innervation of the gut is necessary for duodenal infusions of fat to induce satiety, suggesting that sympathetic activity may engage small-intestinal satiety signals such as OEA and NPPE. In the present study, we show that surgical resection of the sympathetic celiac-superior mesenteric ganglion complex, which sends projections to the upper gut, abolishes feeding-induced OEA production in rat small-intestinal cells. These effects are accounted for by suppression of OEA biosynthesis, and are mimicked by administration of the selective β2-adrenergic receptor antagonist ICI-118,551. We further show that sympathetic ganglionectomy or pharmacological blockade of β2-adrenergic receptors prevents NPPE release into the circulation. In addition, sympathetic ganglionectomy increases meal frequency and lowers satiety ratio, and these effects are corrected by pharmacological administration of OEA. The results suggest that sympathetic activity controls fat-induced satiety by enabling the coordinated production of local (OEA) and systemic (NPPE) satiety signals in the small intestine.
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Oleoylethanolamide: a new player in energy metabolism control. Role in food intake
Drug Discovery Today: Disease Mechanisms, 2010Co-Authors: Pasqua Dipasquale, Adele Romano, Silvia Cianci, Laura Righetti, Silvana GaetaniAbstract:Oleoylethanolamide (OEA) is a lipid amide produced by enterocytes upon the absorption of dietary fat and participates in the induction of satiety. Through indirect pathways, probably depending on the local activation of peroxisome-proliferator-activated receptor-alpha and involving afferent vagus nerve fibers, OEA signal is transmitted to the brain-stem and the hypothalamus, where it stimulates the release of oxytocin from magnocellular neurons. OEA mechanism might, thus, provide a novel target for the design of therapies controlling appetite.
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Oleoylethanolamide: a new player in energy metabolism control. Role in food intake
Drug Discovery Today: Disease Mechanisms, 2010Co-Authors: Pasqua Dipasquale, Adele Romano, Silvia Cianci, Laura Righetti, Silvana GaetaniAbstract:Oleoylethanolamide (OEA) is a lipid amide produced by enterocytes upon the absorption of dietary fat and participates in the induction of satiety. Through indirect pathways, probably depending on the local activation of peroxisome-proliferator-activated receptor-alpha and involving afferent vagus nerve fibers, OEA signal is transmitted to the brain-stem and the hypothalamus, where it stimulates the release of oxytocin from magnocellular neurons. OEA mechanism might, thus, provide a novel target for the design of therapies controlling appetite. © 2011 Elsevier Ltd
