OBJECTIVE Oleoylethanolamide(OEA) is an endogenous peroxisome proliferatoractivated receptor alpha(PPARα) agonist that acts on the peripheral control of energy metabolism.Previous studies have shown that OEA exerts n...OBJECTIVE Oleoylethanolamide(OEA) is an endogenous peroxisome proliferatoractivated receptor alpha(PPARα) agonist that acts on the peripheral control of energy metabolism.Previous studies have shown that OEA exerts neuroprotection after cerebral ischemia.However,whether OEA affects the outcomes of diabetes-induced encephalopathy(DE) requires further study.METHODS The chronic effects of OEA on DE were evaluated in C57BL/6 and PPARαknockout mice,individually.The cognitive function was assessed with Morris water maze.The expression of receptor for advanced glycation end products(RAGE) and phosphorylation of Tau in mice hippocampus were determined using Western blotting.The influence of OEA in neuron loss and neuroplasticity were assessed with immunofluorescent staining and Western blotting.RESULTS OEA markedly ameliorated performance in the Morris water maze,which was correlated with its capabilities of suppressing glycometabolism and phosphorylation of Tau in the hippocampus.OEA offered protection from diabetes-induced impairments in hippocampal neuroplasticity.Furthermore,the changes in Morris water maze performance and neuron loss could not be observed in PPARα knockout mouse models with OEA administration.CONCLUSION The ability of OEA to control PPARα signaling can serve as a novel neuroprotective approach for the treatment of diabetes-induced encephalopathy.展开更多
OBJECTIVE Oleoylethanolamide(OEA) has shown neuroprotective effect in treating acute and chronic ischemic stroke.However,it is unclear whether OEA is able to modulate microglia/macrophage polarization,which has recent...OBJECTIVE Oleoylethanolamide(OEA) has shown neuroprotective effect in treating acute and chronic ischemic stroke.However,it is unclear whether OEA is able to modulate microglia/macrophage polarization,which has recently been documented to be important in the pathology of ischemic stroke.This study explored the potential role of OEA in modulating the microglial phenotypes.METHODS In vivo,middle cerebral artery occlusion(MCAO) was induced in both PPARα-/-(KO) and wild-type(WT)mice.In vitro,primary cortical microglia or neuron or coculture from KO/WT mice was subjected to oxygen glucose deprivation(OGD).Western blotting and immunofluorescence were used for detecting the specialized protein expression of M1/M2,such as CD206 and CD16/32.q PCR was utilized to detect the signature gene change of M1/M2.RESULTS OEA significantly reduced neuron damage of mice after MCAO.More importantly,OEA promoted microglia/macrophage transferring from inflammatory M1 phenotype to a protective,anti-inflammatory M2 phenotype in vivo or in vitro.Interestingly,these benifical effects of OEA could not be observed in the KO mice or KO microglia.CONCLUSION Our results reveal a novel pharmacological effect of OEA in modulating microglia/macrophage polarization after MCAO,thus depening our understanding of neuroprotective mechanisms of OEA in treatment of ischemic stroke.Furthermore,this new mechanism may allow OEA to be used in many other microglia/macrophage polarizationrelated inflammatory diseases.展开更多
Patients undergoing Roux-en-Y gastric bypass(RYGB)surgery elicit striking loss of body weight. Anatomical restructuring of the gastrointestinal(GI) tract, leading to reduced caloric intake and changes in food preferen...Patients undergoing Roux-en-Y gastric bypass(RYGB)surgery elicit striking loss of body weight. Anatomical restructuring of the gastrointestinal(GI) tract, leading to reduced caloric intake and changes in food preference, are thought to be the primary drivers of weight loss in bariatric surgery patients. However, the mechanisms by which RYGB surgery causes a reduced preference for fatty foods remain elusive. In a recent report, Hankir et al described how RYGB surgery modulated lipid nutrient signals in the intestine of rats to blunt their craving for fatty food. The authors reported that RYGB surgery restored an endogenous fat-satiety signaling pathway, mediated via oleoylethanolamide(OEA), that was greatly blunted in obese animals. In RYGB rats, high fat diet(HFD) led to increased production of OEA that activated the intestinal peroxisome proliferation activator receptors-α(PPARα). In RYGB rats, activation of PPARα by OEA was accompanied by enhanced dopamine neurotransmission in the dorsal striatum and reduced preference for HFD. The authors showed that OEA-mediated signals to the midbrain were transmitted via the vagus nerve. Interfering with either the production of OEA in enterocytes, or blocking of vagal and striatal D1 receptors signals eliminated the decreased craving for fat in RYGB rats. These studies demonstrated that bariatric surgery led to alterations in the reward circuitry of the brain in RYGB rats and reduced their preference for HFD.展开更多
基金Fun-damental Research Funds for the Central Universities (20720180042)Health Science ResearchPersonnel Training Program of Fujian Province(2018-CXB-30)+2 种基金Natural Science Foundation of Fujian, China (2016J014152016D024)Science and Technology Project of Xi
文摘OBJECTIVE Oleoylethanolamide(OEA) is an endogenous peroxisome proliferatoractivated receptor alpha(PPARα) agonist that acts on the peripheral control of energy metabolism.Previous studies have shown that OEA exerts neuroprotection after cerebral ischemia.However,whether OEA affects the outcomes of diabetes-induced encephalopathy(DE) requires further study.METHODS The chronic effects of OEA on DE were evaluated in C57BL/6 and PPARαknockout mice,individually.The cognitive function was assessed with Morris water maze.The expression of receptor for advanced glycation end products(RAGE) and phosphorylation of Tau in mice hippocampus were determined using Western blotting.The influence of OEA in neuron loss and neuroplasticity were assessed with immunofluorescent staining and Western blotting.RESULTS OEA markedly ameliorated performance in the Morris water maze,which was correlated with its capabilities of suppressing glycometabolism and phosphorylation of Tau in the hippocampus.OEA offered protection from diabetes-induced impairments in hippocampal neuroplasticity.Furthermore,the changes in Morris water maze performance and neuron loss could not be observed in PPARα knockout mouse models with OEA administration.CONCLUSION The ability of OEA to control PPARα signaling can serve as a novel neuroprotective approach for the treatment of diabetes-induced encephalopathy.
基金Fundamental Research Funds for the Central Universities (20720180042)Health Science ResearchPersonnel Training Program of Fujian Province(2018-CXB-30)+2 种基金Natural Science Foundation of Fujian Province of China (2016J014152016D024)Science and Technology Pro
文摘OBJECTIVE Oleoylethanolamide(OEA) has shown neuroprotective effect in treating acute and chronic ischemic stroke.However,it is unclear whether OEA is able to modulate microglia/macrophage polarization,which has recently been documented to be important in the pathology of ischemic stroke.This study explored the potential role of OEA in modulating the microglial phenotypes.METHODS In vivo,middle cerebral artery occlusion(MCAO) was induced in both PPARα-/-(KO) and wild-type(WT)mice.In vitro,primary cortical microglia or neuron or coculture from KO/WT mice was subjected to oxygen glucose deprivation(OGD).Western blotting and immunofluorescence were used for detecting the specialized protein expression of M1/M2,such as CD206 and CD16/32.q PCR was utilized to detect the signature gene change of M1/M2.RESULTS OEA significantly reduced neuron damage of mice after MCAO.More importantly,OEA promoted microglia/macrophage transferring from inflammatory M1 phenotype to a protective,anti-inflammatory M2 phenotype in vivo or in vitro.Interestingly,these benifical effects of OEA could not be observed in the KO mice or KO microglia.CONCLUSION Our results reveal a novel pharmacological effect of OEA in modulating microglia/macrophage polarization after MCAO,thus depening our understanding of neuroprotective mechanisms of OEA in treatment of ischemic stroke.Furthermore,this new mechanism may allow OEA to be used in many other microglia/macrophage polarizationrelated inflammatory diseases.
文摘Patients undergoing Roux-en-Y gastric bypass(RYGB)surgery elicit striking loss of body weight. Anatomical restructuring of the gastrointestinal(GI) tract, leading to reduced caloric intake and changes in food preference, are thought to be the primary drivers of weight loss in bariatric surgery patients. However, the mechanisms by which RYGB surgery causes a reduced preference for fatty foods remain elusive. In a recent report, Hankir et al described how RYGB surgery modulated lipid nutrient signals in the intestine of rats to blunt their craving for fatty food. The authors reported that RYGB surgery restored an endogenous fat-satiety signaling pathway, mediated via oleoylethanolamide(OEA), that was greatly blunted in obese animals. In RYGB rats, high fat diet(HFD) led to increased production of OEA that activated the intestinal peroxisome proliferation activator receptors-α(PPARα). In RYGB rats, activation of PPARα by OEA was accompanied by enhanced dopamine neurotransmission in the dorsal striatum and reduced preference for HFD. The authors showed that OEA-mediated signals to the midbrain were transmitted via the vagus nerve. Interfering with either the production of OEA in enterocytes, or blocking of vagal and striatal D1 receptors signals eliminated the decreased craving for fat in RYGB rats. These studies demonstrated that bariatric surgery led to alterations in the reward circuitry of the brain in RYGB rats and reduced their preference for HFD.
