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Monoacylglycerol Lipase Regulates Fever Response.

Sanchez-Alavez M, Nguyen W, Mori S, Moroncini G, Viader A, Nomura DK, Cravatt BF, Conti B - PLoS ONE (2015)

Bottom Line: Cyclooxygenase inhibitors such as ibuprofen have been used for decades to control fever through reducing the levels of the pyrogenic lipid transmitter prostaglandin E2 (PGE2).We also show that a cannabinoid CB1 receptor antagonist does not attenuate these anti-pyrogenic effects of MAGL inhibitors.Thus, much like traditional nonsteroidal anti-inflammatory drugs, MAGL inhibitors can control fever, but appear to do so through restricted control over prostaglandin production in the nervous system.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemical Physiology, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA, 92037, United States of America.

ABSTRACT
Cyclooxygenase inhibitors such as ibuprofen have been used for decades to control fever through reducing the levels of the pyrogenic lipid transmitter prostaglandin E2 (PGE2). Historically, phospholipases have been considered to be the primary generator of the arachidonic acid (AA) precursor pool for generating PGE2 and other eicosanoids. However, recent studies have demonstrated that monoacyglycerol lipase (MAGL), through hydrolysis of the endocannabinoid 2-arachidonoylglycerol, provides a major source of AA for PGE2 synthesis in the mammalian brain under basal and neuroinflammatory states. We show here that either genetic or pharmacological ablation of MAGL leads to significantly reduced fever responses in both centrally or peripherally-administered lipopolysaccharide or interleukin-1β-induced fever models in mice. We also show that a cannabinoid CB1 receptor antagonist does not attenuate these anti-pyrogenic effects of MAGL inhibitors. Thus, much like traditional nonsteroidal anti-inflammatory drugs, MAGL inhibitors can control fever, but appear to do so through restricted control over prostaglandin production in the nervous system.

No MeSH data available.


Related in: MedlinePlus

Mgll-/- and Mgll+/+ mice have similar core body temperature profiles.CBT profile of Mgll-/- and Mgll+/+ male mice over 24 hrs. No statistically significant differences were observed across genotypes. Data are shown as mean ± sem, n = 6 mice per group, p>0.05.
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pone.0134437.g001: Mgll-/- and Mgll+/+ mice have similar core body temperature profiles.CBT profile of Mgll-/- and Mgll+/+ male mice over 24 hrs. No statistically significant differences were observed across genotypes. Data are shown as mean ± sem, n = 6 mice per group, p>0.05.

Mentions: Before investigating the possible role of MAGL in fever, we compared the profile of core body temperature (CBT) of Mgll-/- and Mgll+/+ mice. No difference in CBT was observed across genotypes over a 24 hour period of recording (Fig 1). Both groups of animals showed similar and normal CBT profiles in the dark (active part of the day, 12 to 24 hrs), in the light (resting part of the day, 0 to 12 hrs) and during the transitions between phases. This indicates that MAGL is not required for the maintenance of the basal CBT and temperature homeostasis and identify Mgll-/- mice as a suitable model to investigate the role of MAGL in fever.


Monoacylglycerol Lipase Regulates Fever Response.

Sanchez-Alavez M, Nguyen W, Mori S, Moroncini G, Viader A, Nomura DK, Cravatt BF, Conti B - PLoS ONE (2015)

Mgll-/- and Mgll+/+ mice have similar core body temperature profiles.CBT profile of Mgll-/- and Mgll+/+ male mice over 24 hrs. No statistically significant differences were observed across genotypes. Data are shown as mean ± sem, n = 6 mice per group, p>0.05.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4543552&req=5

pone.0134437.g001: Mgll-/- and Mgll+/+ mice have similar core body temperature profiles.CBT profile of Mgll-/- and Mgll+/+ male mice over 24 hrs. No statistically significant differences were observed across genotypes. Data are shown as mean ± sem, n = 6 mice per group, p>0.05.
Mentions: Before investigating the possible role of MAGL in fever, we compared the profile of core body temperature (CBT) of Mgll-/- and Mgll+/+ mice. No difference in CBT was observed across genotypes over a 24 hour period of recording (Fig 1). Both groups of animals showed similar and normal CBT profiles in the dark (active part of the day, 12 to 24 hrs), in the light (resting part of the day, 0 to 12 hrs) and during the transitions between phases. This indicates that MAGL is not required for the maintenance of the basal CBT and temperature homeostasis and identify Mgll-/- mice as a suitable model to investigate the role of MAGL in fever.

Bottom Line: Cyclooxygenase inhibitors such as ibuprofen have been used for decades to control fever through reducing the levels of the pyrogenic lipid transmitter prostaglandin E2 (PGE2).We also show that a cannabinoid CB1 receptor antagonist does not attenuate these anti-pyrogenic effects of MAGL inhibitors.Thus, much like traditional nonsteroidal anti-inflammatory drugs, MAGL inhibitors can control fever, but appear to do so through restricted control over prostaglandin production in the nervous system.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemical Physiology, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA, 92037, United States of America.

ABSTRACT
Cyclooxygenase inhibitors such as ibuprofen have been used for decades to control fever through reducing the levels of the pyrogenic lipid transmitter prostaglandin E2 (PGE2). Historically, phospholipases have been considered to be the primary generator of the arachidonic acid (AA) precursor pool for generating PGE2 and other eicosanoids. However, recent studies have demonstrated that monoacyglycerol lipase (MAGL), through hydrolysis of the endocannabinoid 2-arachidonoylglycerol, provides a major source of AA for PGE2 synthesis in the mammalian brain under basal and neuroinflammatory states. We show here that either genetic or pharmacological ablation of MAGL leads to significantly reduced fever responses in both centrally or peripherally-administered lipopolysaccharide or interleukin-1β-induced fever models in mice. We also show that a cannabinoid CB1 receptor antagonist does not attenuate these anti-pyrogenic effects of MAGL inhibitors. Thus, much like traditional nonsteroidal anti-inflammatory drugs, MAGL inhibitors can control fever, but appear to do so through restricted control over prostaglandin production in the nervous system.

No MeSH data available.


Related in: MedlinePlus