A role of CB1R in inducing θ-rhythm coordination between the gustatory and gastrointestinal insula

Abstract

Anandamide (AEA) and N-oleoylethanolamine (OEA) are produced in the intestine and brain during fasting and satiety, respectively. Subsequently, AEA facilitates food intake via activation of cannabinoid type-1 receptors (CB1Rs) while OEA decreases food intake via activation of peroxisome proliferator-activated receptor-α (PPARα) and/or G-protein-coupled receptor 119 (GPR119). Neuronal activity in the gastrointestinal region of the autonomic insula (GI-Au-I) that rostrally adjoins the gustatory insula (Gu-I) increases during fasting, enhancing appetite while umami and sweet taste sensations in Gu-I enhances appetite in GI-Au-I, strongly suggesting the presence of a neural interaction between the Gu-I and GI-Au-I which changes depending on the concentrations of AEA and OEA. However, this possibility has never been investigated. In rat slice preparations, we demonstrate with voltage-sensitive dye imaging that activation of CB1Rs by AEA induces θ-rhythm oscillatory synchronization in the Gu-I which propagates into the GI-Au-I but stops at its caudal end, displaying an oscillatory coordination. The AEA-induced oscillation was abolished by a CB1R antagonist or OEA through activation of GPR119. Our results demonstrate that the neural coordination between the Gu-I and GI-Au-I is generated or suppressed by the opposing activities between CB1R and GPR119. This mechanism may be involved in the feeding behavior based on taste recognition.

Leptogenic effects of NAPE require activity of NAPE-hydrolyzing phospholipase D

“…Unrelated agonists of these receptors induce leptogenic effects (26)(27)(28)(29)(30). Potential downstream pathways from these receptors, including induction of stimulation of lipolysis in adipocytes by PPAR activation (44), inhibition of SCD-1 by activation of PPAR (45,46), activation of kinases by PPAR (47), repression of nitric oxide signaling by PPAR (18), induction of white adipose remodeling to beige adipose by PPAR activation (48), induction of hypothalamic oxytocin secretion by PPAR-mediated stimulation of vagal fibers (49,50), GLP-1 secretion from enteroendocrine L cells induced by GPR119 activation (20,51), enhancement of GLP1 receptor activation by direct binding of OEA to GLP-1 (52), inhibition of CB 1 -mediated activation of gustatory insula by GPR119 activation (53), and induction of vagal nerve currents via TRPV1 activation (54). Despite these significant advances in our understanding of how the NAEs can exert the broad range of leptogenic effects attributed to the NAPE/NAE pathway, additional studies are clearly still needed.…”

Therapeutic application of GPR119 ligands in metabolic disorders

“…Considering the preceding articles, inconsistencies in these results may result from differences in detection sensitivity as a result of the very low levels of hepatic expression or of the age difference. A recent study demonstrated that chemosensory sensation in the insular cortex was under the control of GPR119 signaling and the presence of GPR119 in the gustatory insula was confirmed by immunohistochemical staining in SD rats …”

“…Proposed signaling pathway(s) and physiological/pharmacological effects of GPR119 activation in diverse tissues . Abbreviations: ABCA1, ATP‐binding cassette subfamily A1; ACC, acetyl‐CoA carboxylase; AMPK, AMP‐activated protein kinase; CB1, cannabinoid receptor type 1; CPT1, carnitine palmitoyltransferase‐1; CTGF, connective tissue growth factor; FAS, fatty acid synthase; GIP, glucose‐dependent insulinotropic peptide; GLP‐1, glucagon‐like peptide‐1; Gαs, stimulatory G protein α‐subunit; NFATc1, nuclear factor of activated T cells, cytoplasmic 1; OEA, oleoylethanolamide; Ox‐LDL, oxidized low‐density lipoprotein; PDK4, pyruvate dehydrogenase kinase isozyme 4; PGC1α, peroxisome proliferator‐activated receptor‐α coactivator 1‐α; PKA, protein kinase A; PPARα, peroxisome proliferator‐activated receptor‐α; SCD1, stearoyl‐CoA desaturase‐1; SREBP‐1, sterol regulatory element binding protein‐1…”

“…5 The islets Proposed signaling pathway(s) and physiological/pharmacological effects of GPR119 activation in diverse tissues. 5,6,[13][14][15][16][17][18][19][20][21][22] Abbreviations: ABCA1, ATP-binding cassette subfamily A1; ACC, acetyl-CoA carboxylase; AMPK, AMP-activated protein kinase; CB1, cannabinoid receptor type 1; CPT1, carnitine palmitoyltransferase-1; CTGF, connective tissue growth factor; FAS, fatty acid synthase; GIP, glucose-dependent insulinotropic peptide; GLP-1, glucagon-like peptide-1; Gαs, stimulatory G protein α-subunit; NFATc1, nuclear factor of activated T cells, cytoplasmic 1; OEA, oleoylethanolamide; Ox-LDL, oxidized low-density lipoprotein; PDK4, pyruvate dehydrogenase kinase isozyme 4; PGC1α, peroxisome proliferator-activated receptor-α coactivator 1-α; PKA, protein kinase A; PPARα, peroxisome proliferatoractivated receptor-α; SCD1, stearoyl-CoA desaturase-1; SREBP-1, sterol regulatory element binding protein-1 in GPR119-deficient mice were also normal in terms of morphology and response to glucose and GLP-1, 5 but glucose-induced GLP-1 secretion was reduced. 18 Interestingly, GLP-1 secretion stimulated by triglycerides was significantly attenuated in GPR119-deficient mice, but not in FFAR1-or FFAR4-deficient mice, suggesting the essential role of GPR119 in the regulation of GLP-1 release.…”

“…A recent study demonstrated that chemosensory sensation in the insular cortex was under the control of GPR119 signaling and the presence of GPR119 in the gustatory insula was confirmed by immunohistochemical staining in SD rats. 17 Little et al demonstrated that the absolute levels of GPR119 transcripts extracted from human duodenal mucosal biopsies correlated negatively with body mass index (BMI). 28 In line with this, the number of duodenal GLP-1-expressing cells decreased as BMI increased.…”