Deletion of G-protein-coupled receptor 55 promotes obesity by reducing physical activity

Meadows, A.; Lee, J. H.; Wu, Chia-Shan; Wei, Qiong; Pradhan, Geetali; Yafi, Michael; Lu, Hui-Chen; Sun, Yuxiang

doi:10.1038/ijo.2015.209

Cited by 56 publications

(73 citation statements)

References 63 publications

(79 reference statements)

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“…administration of the atypical cannabinoid O-1602 acutely stimulates food intake in rats, a parallel experiment performed in GPR55 −/− mice revealed that effect of O-1602 on food consumption was independent of GPR55 (Diaz-Arteaga et al 2012). Moreover, Gpr55 −/− mice did not exhibit different food intake compared to their control littermates (Bjursell et al 2016, Meadows et al 2016. Nonetheless, the fact that a dysfunctional alteration of the Gpr55 gene is associated to increased vulnerability to anorexia nervosa in Japanese women, suggests that Gpr55 plays a role in the regulation of feeding behavior (Ishiguro et al 2011).…”

Section: Metabolic Actions Of Gpr55 In the Cnsmentioning

confidence: 97%

“…However, studies employing Gpr55 −/− mice report different effects of GPR55 on glucose metabolism (Table 1). Mice globally lacking Gpr55 showed slightly impaired glucose tolerance (Song et al 2012), whereas a more recent report showed normal glucose tolerance in Gpr55 −/− mice with no differences in GSIS (Meadows et al 2016). The lack of methodological information impedes to decipher the factor/s (i.e.…”

Section: Metabolic Actions Of Gpr55 In the Islets Of Langerhansmentioning

confidence: 99%

“…Genetic GPR55 ablation leads to increased adiposity (Meadows et al 2016) and, accordingly, obese rodent models including mice lacking leptin (ob/ob mice) and rats fed a high-fat diet (HFD) showed decreased WAT GPR55 expression (Moreno-Navarrete et al 2012). Such potentiation of adiposity may result, at least in part, from reduced physical activity (Meadows et al 2016); however, other factors might also be involved. Díaz-Arteaga and coworkers showed decreased mobilization of fatty acids after either central or peripheral sub-chronic O-1602 treatment in rats .…”

Section: Metabolic Actions Of Gpr55 In Watmentioning

confidence: 99%

“…Nonetheless, the fact that a dysfunctional alteration of the Gpr55 gene is associated to increased vulnerability to anorexia nervosa in Japanese women, suggests that Gpr55 plays a role in the regulation of feeding behavior (Ishiguro et al 2011). Although the extent to which GPR55 modulates food consumption is unclear, phenotyping studies using Gpr55 −/− mice showed decreased energy expenditure and spontaneous locomotor activity, which results in increased fat mass and leptin levels, as well as in insulin resistance (Meadows et al 2016) (Table 1), a trend toward obesity. In addition, the chronic i.c.v.…”

Section: Metabolic Actions Of Gpr55 In the Cnsmentioning

confidence: 99%

“…Given its extensive distribution in the brain, GPR55 participates in a number of physiological processes that include movement coordination and motor activity (Wu et al 2013, Bjursell et al 2016, nociception (Deliu et al 2015), modulation of anxiety-like behaviors (Rahimi et al 2015), as well as energy expenditure (Bjursell et al 2016, Meadows et al 2016 (Fig. 1).…”

Section: Metabolic Actions Of Gpr55 In the Cnsmentioning

confidence: 99%

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GPR55: a new promising target for metabolism?

Tudurí

Imbernón

Hernández-Bautista

et al. 2017

Journal of Molecular Endocrinology

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GPR55 is a G-protein-coupled receptor (GPCR) that has been identified as a new cannabinoid receptor. Given the wide localization of GPR55 in brain and peripheral tissues, this receptor has emerged as a regulator of multiple biological actions. Lysophosphatidylinositol (LPI) is generally accepted as the endogenous ligand of GPR55. In this review, we will focus on the role of GPR55 in energy balance and glucose metabolism. We will summarize its actions on feeding, nutrient partitioning, gastrointestinal motility and insulin secretion in preclinical models and the scarce data available in humans. The potential of GPR55 to become a new pharmaceutical target to treat obesity and type 2 diabetes, as well as the foreseeing difficulties are also discussed.

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Section: Metabolic Actions Of Gpr55 In the Cnsmentioning

confidence: 97%

Section: Metabolic Actions Of Gpr55 In the Islets Of Langerhansmentioning

confidence: 99%

Section: Metabolic Actions Of Gpr55 In Watmentioning

confidence: 99%

Section: Metabolic Actions Of Gpr55 In the Cnsmentioning

confidence: 99%

Section: Metabolic Actions Of Gpr55 In the Cnsmentioning

confidence: 99%

See 3 more Smart Citations

GPR55: a new promising target for metabolism?

Tudurí

Imbernón

Hernández-Bautista

et al. 2017

Journal of Molecular Endocrinology

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The L‐α‐Lysophosphatidylinositol/G Protein–Coupled Receptor 55 System Induces the Development of Nonalcoholic Steatosis and Steatohepatitis

et al. 2020

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BaCKgRoUND aND aIMS: G protein-coupled receptor (GPR) 55 is a putative cannabinoid receptor, and l-αlysophosphatidylinositol (LPI) is its only known endogenous ligand. Although GPR55 has been linked to energy homeostasis in different organs, its specific role in lipid metabolism in the liver and its contribution to the pathophysiology of nonalcoholic fatty liver disease (NAFLD) remains unknown. appRoaCH aND ReSUltS: We measured (1) GPR55 expression in the liver of patients with NAFLD compared with individuals without obesity and without liver disease, as well as animal models with steatosis and nonalcoholic steatohepatitis (NASH), and (2) the effects of LPI and genetic disruption of GPR55 in mice, human hepatocytes, and human hepatic stellate cells. Notably, we found that circulating LPI and liver expression of GPR55 were up-regulated in patients with NASH. LPI induced adenosine monophosphate-activated protein kinase activation of acetyl-coenzyme A carboxylase (ACC) and increased lipid content in human hepatocytes and in the liver of treated mice by inducing de novo lipogenesis and decreasing β-oxidation. The inhibition of GPR55 and ACCα blocked the effects of LPI, and the in vivo knockdown of GPR55 was sufficient to improve liver damage in mice fed a high-fat diet and in mice fed a methionine-choline-deficient diet. Finally, LPI promoted the initiation of hepatic stellate cell activation by stimulating GPR55 and activation of ACC. CoNClUSIoNS: The LPI/GPR55 system plays a role in the development of NAFLD and NASH by activating ACC. (Hepatology 2020;0:1-19). N onalcoholic fatty liver (NAFL) disease (NAFLD) is a major global health threat because of its growing incidence and prevalence. It is becoming the leading cause of liver disease and despite the many efforts to find therapeutic targets for this disease, there is no established therapy yet.

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A putative lysophosphatidylinositol receptor GPR55 modulates hippocampal synaptic plasticity

et al. 2017

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GPR55, an orphan G-protein coupled receptor, is activated by lysophosphatidylinositol (LPI) and the endocannabinoid anandamide, as well as by other compounds including THC. Such signaling molecules are capable of modulating synaptic plasticity. LPI is a potent endogenous ligand of GPR55 and neither GPR55 nor LPIs’ functions in the brain are well understood. While endocannabinoids are well known to modulate brain synaptic plasticity, the potential role LPI could have on brain plasticity has never been demonstrated. Therefore, we examined not only GPR55 expression, but also the role its endogenous ligand could play in long-term potentiation, a common form of synaptic plasticity. Using quantitative RT-PCR, electrophysiology, and behavioral assays, we examined hippocampal GPR55 expression and function. qRT-PCR results indicate that GPR55 is expressed in hippocampi of both rats and mice. Immunohistochemistry and single cell PCR demonstrates GPR55 protein in pyramidal cells of CA1 and CA3 layers in the hippocampus. Application of the GPR55 endogenous agonist LPI to hippocampal slices of GPR55+/+ mice significantly enhanced CA1 LTP. This effect was absent in GPR55−/− mice, and blocked by the GPR55 antagonist CID 16020046. We also examined paired-pulse ratios of GPR55−/− and GPR55+/+ mice with or without LPI and noted significant enhancement in paired-pulse ratios by LPI in GPR55+/+ mice. Behaviorally, GPR55−/− and GPR55+/+ mice did not differ in memory tasks including novel object recognition, radial arm maze, or Morris water maze. However, performance on radial arm maze and elevated plus maze task suggests GPR55−/− mice have a higher frequency of immobile behavior. This is the first demonstration of LPI involvement in hippocampal synaptic plasticity.

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Deletion of G-protein-coupled receptor 55 promotes obesity by reducing physical activity

Abstract: GPR55 has an important role in energy homeostasis. GPR55 ablation increases adiposity and insulin resistance by selectively decreasing physical activity, but not by altering feeding behavior as CB1.

Cited by 56 publications

References 63 publications

GPR55: a new promising target for metabolism?

GPR55: a new promising target for metabolism?

The L‐α‐Lysophosphatidylinositol/G Protein–Coupled Receptor 55 System Induces the Development of Nonalcoholic Steatosis and Steatohepatitis

A putative lysophosphatidylinositol receptor GPR55 modulates hippocampal synaptic plasticity

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