Chronic oleoylethanolamide treatment attenuates diabetes-induced mice encephalopathy by triggering peroxisome proliferator-activated receptor alpha in the hippocampus

Ren, Tong; Liu, Jinfeng; Ge, Yunlong; Zhuo, Rengong; Lu, Peng; Feng, Li; Jin, Xin; Yang, Lichao

doi:10.1016/j.neuint.2019.104501

Cited by 18 publications

(12 citation statements)

References 47 publications

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“…To further confirm the antidiabetic effects of OEA in vivo, HFD/STZ diabetic rats were administered OEA for 6 weeks. Consistent with the effect of OEA on supressing plasma glucose in HFD/ STZ-induced mice (Ren et al, 2019), OEA treatment dosedependently decreased plasma glucose concentrations after 8-hour fasting in diabetic rats (Fig. 1A).…”

Section: Resultssupporting

confidence: 82%

“…OEA Ameliorated the HFD/STZ-Induced Hyperglycemia in a PPARa-Independent Manner. Our latest study indicated that OEA inhibited the elevation of plasma glucose in HFD/STZ-induced mice (Ren et al, 2019). To further confirm the antidiabetic effects of OEA in vivo, HFD/STZ diabetic rats were administered OEA for 6 weeks.…”

Section: Resultsmentioning

confidence: 98%

“…OEA regulates glucose uptake in isolated adipocytes (Guzmán et al, 2004). Our latest research demonstratea that OEA suppressed plasma glucose and reduced hippocampal disturbances of glycose metabolism in diabetic mice (Ren et al, 2019). However, the role of PPARa in OEA regulation of glucose metabolism is not clear.…”

Section: Discussionmentioning

confidence: 99%

“…Hepatocytes express more PPARa than adipocytes. Our previous study showed that OEA ameliorated diabetes-induced cognitive deficits via a PPARa-mediated pathway (Ren et al, 2019). Whether PPARa is a key target for the effect of OEA on hepatocyte glucose metabolism balance is not clear.…”

Section: Introductionmentioning

confidence: 98%

“…In addition, the liver is a main target organ for the regulation of glucose metabolism via regulating gluconeogenesis and glycogen synthesis. Furthermore, our latest study indicates that OEA exerted antidiabetic effects in high-fat diet (HFD) and streptozotocin (STZ)-induced mice (Ren et al, 2019). However, it is unclear whether OEA inhibits the elevation of blood sugar by regulating hepatic gluconeogenesis and glycogen synthesis.…”

Section: Introductionmentioning

confidence: 99%

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Oleoylethanolamide Increases Glycogen Synthesis and Inhibits Hepatic Gluconeogenesis via the LKB1/AMPK Pathway in Type 2 Diabetic Model

Ren

Zhuo

et al. 2020

J Pharmacol Exp Ther

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Oleoylethanolamide (OEA) is an endogenous peroxisome proliferatoractivated receptor a (PPARa) 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 PPARa-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)/59 AMP-activated protein kinase (AMPK) signaling pathways. PPARa 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 STATEMENTOleoylethanolamide (OEA) exerted a potent antihyperglycemic effect in a peroxisome proliferator-activated receptor a-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 B1/59 AMPactivated protein kinase signaling pathways.

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Section: Resultssupporting

confidence: 82%

Section: Resultsmentioning

confidence: 98%