G protein-coupled receptor 12 deficiency results in dyslipidemia and obesity in mice

Bjursell, Mikael; Gerdin, Anna-Karin; Jönsson, Marie E.; Surve, Vikas; Svensson, Lennart; Huang, Xu‐Feng; Törnell, Jan; Bohlooly‐Y, Mohammad

doi:10.1016/j.bbrc.2006.07.090

Cited by 36 publications

(40 citation statements)

References 27 publications

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“…Therefore, the uncharacterized orphan GPCRs can be expected to represent possible novel therapeutic targets in the future [15]. The GPR12 homologue was initially cloned from rat pituitary gland [16] and human GPR12 was cloned in 1995 [17].…”

Section: Discussionmentioning

confidence: 99%

Two New 5-Hydroxy-2-pyrone Derivatives Isolated from a Marine-derived Fungus Aspergillus flavus

Lin

Fang

et al. 2008

J Antibiot

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Two new compounds, 4-(hydroxymethyl)-5-hydroxy-2H-pyran-2-one (1) and (5-hydroxy-2-oxo-2H-pyran-4-yl) methyl acetate (2), have been isolated from a marine-derived fungus Aspergillus flavus. Their structures were determined by spectroscopic data. Compound 1 induced the production of cAMP on GPR12 transfected CHO and HEK293 cells in a dose-dependent manner, which indicated 1 might be a possible ligand for GPR12.Keywords marine-derived fungus, Aspergillus flavus, 5-hydroxy-2-pyrone, cAMP, GPR12 Introduction 2-Pyrone is a six-membered cyclic unsaturated ester, which is highly abundant in bacteria, microbial, plant, insect and animal systems and takes part in many different types of biological processes such as defence against other organisms, as key biosynthetic intermediates, and as metabolites [1]. A wide range of bioactivities such as plant growth-regulating [2,3], antitumour [4,5], antimicrobial and antifungal activities [6,7] have demonstrated the medicinal importance of 2-pyrones. In our search for new bioactive compounds from the marine-derived fungus Aspergillus flavus c-f-3 separated from a marine algae sample collected in Putian Pinghai, China, two new 5-hydroxy-2-pyrone derivatives (1, 2) were isolated. The biological activities of 1 and 2 were tested using cAMP assay in GPR12 transfected CHO and HEK293 cells. In this paper we described the isolation and structure elucidation of 1 and 2 (Fig. 1) as well as their bioactivities. Materials and Methods MicroorganismThe Aspergillus flavus c-f-3 was separated from a marine algae Enteromorpha tubulosa, collected at Putian Pinghai, China, in August, 2005, using dilution-plate method [8] on PDA medium [9]. It was identified according to its morphological characteristic by Prof. Hong Kui (the Chinese Academy of Tropical Agricultural Sciences, Hainan, China). Working stocks were prepared on Potato Dextrose agar slants stored at 4°C. Two New 5-Hydroxy-2-pyrone Derivatives Isolated from a Marine-derived Fungus

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Section: Discussionmentioning

confidence: 99%

Two New 5-Hydroxy-2-pyrone Derivatives Isolated from a Marine-derived Fungus Aspergillus flavus

Lin

Fang

et al. 2008

J Antibiot

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show abstract

“…To evaluate whether GPR12 plays a role in metabolism, GPR12-deficient mice were studied. These mice were found to be obese and dyslipidemic with reduced energy expenditure and decreased res-piratory quotient, while food intake was not different from wild-type mice (Bjursell et al, 2006). Basal insulin levels were reduced and glucose was elevated, suggesting that GPR12 is needed for glucose homeostasis.…”

Section: Gpr12mentioning

confidence: 95%

G-protein-coupled receptors and islet function—Implications for treatment of type 2 diabetes

Winzell

Åhrén

2007

Pharmacology & Therapeutics

161

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Islet function is regulated by a number of different signals. A main signal is generated by glucose, which stimulates insulin secretion and inhibits glucagon secretion. The glucose effects are modulated by many factors, including hormones, neurotransmitters and nutrients. Several of these factors signal through guanine nucleotide-binding protein (G-protein) coupled receptors (GPCRs). Examples of islet GPCRs are GPR40 and GPR119, which are GPCRs with fatty acids as ligands, the receptors for the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), the receptors for the islet hormones glucagon and somatostatin, the receptors for the classical neurotransmittors

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“…GPR3,GPR6, and GPR12 are constitutively active proteins that signal through G␣ s to increase cAMP levels in cells expressing these receptors (Tanaka et al, 2007). They are mainly expressed in the central nervous system, where they may contribute to the regulation of neuronal proliferation (Tanaka et al, 2009), monoamine neurotransmission (Valverde et al, 2009), reward learning processes (Lobo et al, 2007), and energy expenditure (Bjursell et al, 2006). They may also be involved in the regulation of meiosis in oocytes (Hinckley et al, 2005).…”

Section: Gpr84 and Gpr120mentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid Receptors and Their Ligands: Beyond CB₁and CB₂

Howlett²,

et al. 2010

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G protein-coupled receptor 12 deficiency results in dyslipidemia and obesity in mice

Cited by 36 publications

References 27 publications

Two New 5-Hydroxy-2-pyrone Derivatives Isolated from a Marine-derived Fungus Aspergillus flavus

Two New 5-Hydroxy-2-pyrone Derivatives Isolated from a Marine-derived Fungus Aspergillus flavus

G-protein-coupled receptors and islet function—Implications for treatment of type 2 diabetes

International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid Receptors and Their Ligands: Beyond CB₁and CB₂

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G protein-coupled receptor 12 deficiency results in dyslipidemia and obesity in mice

Cited by 36 publications

References 27 publications

Two New 5-Hydroxy-2-pyrone Derivatives Isolated from a Marine-derived Fungus Aspergillus flavus

Two New 5-Hydroxy-2-pyrone Derivatives Isolated from a Marine-derived Fungus Aspergillus flavus

G-protein-coupled receptors and islet function—Implications for treatment of type 2 diabetes

International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid Receptors and Their Ligands: Beyond CB1and CB2

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International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid Receptors and Their Ligands: Beyond CB₁and CB₂