Search results for "G-Protein-Coupled"
showing 10 items of 110 documents
Bile acid receptor TGR5 is critically involved in preference for dietary lipids and obesity
2020
International audience; We investigated the implication of Takeda G protein-coupled receptor 5 (TGR5) in fat preference and fat sensing in taste bud cells (TBC) in C57BL/6 wild-type (WT) and TGR5 knock out (TGR5-/-) male mice maintained for 20 weeks on a high-fat diet (HFD). We also assessed the implication of TGR5 single nucleotide polymorphism (SNP) in young obese humans. The high-fat diet (HFD)-fed TGR5-/- mice were more obese, marked with higher liver weight, lipidemia and steatosis than WT obese mice. The TGR5-/- obese mice exhibited high daily food/energy intake, fat mass and inflammatory status. WT obese mice lost the preference for dietary fat, but the TGR5-/- obese mice exhibited n…
Vitamin C blocks inflammatory platelet-activating factor mimetics created by cigarette smoking.
1997
Cigarette smoking within minutes induces leukocyte adhesion to the vascular wall and formation of intravascular leukocyte-platelet aggregates. We find this is inhibited by platelet-activating factor (PAF) receptor antagonists, and correlates with the accumulation of PAF-like mediators in the blood of cigarette smoke-exposed hamsters. These mediators were PAF-like lipids, formed by nonenzymatic oxidative modification of existing phospholipids, that were distinct from biosynthetic PAF. These PAF-like lipids induced isolated human monocytes and platelets to aggregate, which greatly increased their secretion of IL-8 and macrophage inflammatory protein-1alpha. Both events were blocked by a PAF r…
The Lipid-Sensor Candidates CD36 and GPR120 Are Differentially Regulated by Dietary Lipids in Mouse Taste Buds: Impact on Spontaneous Fat Preference
2011
BACKGROUND: Recent studies in rodents and humans suggest that the chemoreception of long-chain fatty acids (LCFA) in oral cavity is involved in the spontaneous preference for fatty foods and might contribute to the obesity risk. CD36 and GPR120 are LCFA receptors identified in rodent taste bud cells. The fact that CD36 or GPR120 gene inactivation leads to a decrease in the preference for lipids raises the question of the respective role(s) played by these gustatory lipid-sensor candidates. METHODOLOGY/PRINCIPAL FINDINGS: Using a combination of biochemical, nutritional and behavioural studies in wild-type, CD36(+/-)and CD36(-/-) mice, it was found that: 1°) CD36 and GPR120 display different …
CD36 and taste of fat.
2012
Purpose of review This review explores the recent literature on the role of CD36 in the taste of fat, eating behavior and obesity risk in rodents and humans. Recent findings During the last decade, evidence was accumulated supporting the existence of a taste of fat responsible for the spontaneous preference for lipid-rich foods. Surprisingly, the multifunctional membrane-associated protein CD36 appears to play a significant role in this system in rodents. Recently, another plausible gustatory lipid sensor, the GPR120, was also identified in mice, revealing that the mechanism involved in oral fat detection is more complex than initially expected. Interestingly, lingual CD36 and GPR120 displa…
Ca2+ signaling in taste bud cells and spontaneous preference for fat: Unresolved roles of CD36 and GPR120
2013
Recent compelling evidences from rodent and human studies raise the possibility for an additional sixth taste modality devoted to oro-gustatory perception of dietary lipids. Understanding the mechanisms underlying oro-gustatory detection of dietary fat is critical for the prevention and treatment of obesity. A number of studies have suggested that lingual CD36, a glycoprotein, highly expressed by circumvallate papillae of the tongue, is implicated in the perception of dietary fat taste. G protein-coupled receptors (GPCRs) are important signaling molecules for many aspects of cellular functions. It has been shown that these receptors, particularly GPR120, are also involved in lipid taste per…
Lipid-mediated release of GLP-1 by mouse taste buds from circumvallate papillae: putative involvement of GPR120 and impact on taste sensitivity
2012
Glucagon-like peptide-1 (GLP-1) signaling modulates sweet-taste sensitivity in the mouse. Because circumvallate papillae (CVPs) express both GLP-1 and its receptor, a local regulation has been suggested. However, whether dietary lipids are involved in this regulation, as shown in the gut, is unknown. By using a combination of biochemical, immunohistochemical, and behavioral approaches, the present data i) confirm the role of GLP-1 signaling in the attraction for sucrose, ii) demonstrate that minute quantities of long-chain FAs (LCFAs) reinforce the attraction for sucrose in a GLP-1 receptor-dependent manner, iii) suggest an involvement of the LCFA receptor GPR120 expressed in taste buds in …
Allergen-induced IgE-dependent gut inflammation in a human PBMC-engrafted murine model of allergy.
2011
Background Humanized murine models comprise a new tool to analyze novel therapeutic strategies for allergic diseases of the intestine. Objective In this study we developed a human PBMC–engrafted murine model of allergen-driven gut inflammation and analyzed the underlying immunologic mechanisms. Methods Nonobese diabetic (NOD)– scid -γc −/− mice were injected intraperitoneally with human PBMCs from allergic donors together with the respective allergen or not. Three weeks later, mice were challenged with the allergen orally or rectally, and gut inflammation was monitored with a high-resolution video miniendoscopic system, as well as histologically. Results Using the aeroallergens birch or gra…
Anti-inflammatory lipoxin A4 is an endogenous allosteric enhancer of CB1 cannabinoid receptor.
2012
Allosteric modulation of G-protein–coupled receptors represents a key goal of current pharmacology. In particular, endogenous allosteric modulators might represent important targets of interventions aimed at maximizing therapeutic efficacy and reducing side effects of drugs. Here we show that the anti-inflammatory lipid lipoxin A 4 is an endogenous allosteric enhancer of the CB 1 cannabinoid receptor. Lipoxin A 4 was detected in brain tissues, did not compete for the orthosteric binding site of the CB 1 receptor (vs. 3 H-SR141716A), and did not alter endocannabinoid metabolism (as opposed to URB597 and MAFP), but it enhanced affinity of anandamide at the CB1 receptor, thereby potentiating …
Selectivity of pharmacological tools: implications for use in cell physiology. A Review in the Theme: Cell Signaling: Proteins, Pathways and Mechanis…
2014
Pharmacological inhibitors are frequently used to identify the receptors, receptor subtypes, and associated signaling pathways involved in physiological cell responses. Based on the effects of such inhibitors conclusions are drawn about the involvement of their assumed target or lack thereof. While such inhibitors can be useful tools for a better physiological understanding, their uncritical use can lead to incorrect conclusions. This article reviews the concept of inhibitor selectivity and its implication for cell physiology. Specifically, we discuss the implications of using inhibitor vs. activator approaches, issues of direct vs. indirect pathway modulation, implications of inverse agoni…
Hunting for the high-affinity state of G-protein-coupled receptors with agonist tracers: Theoretical and practical considerations for positron emissi…
2019
Abstract The concept of the high‐affinity state postulates that a certain subset of G‐protein‐coupled receptors is primarily responsible for receptor signaling in the living brain. Assessing the abundance of this subset is thus potentially highly relevant for studies concerning the responses of neurotransmission to pharmacological or physiological stimuli and the dysregulation of neurotransmission in neurological or psychiatric disorders. The high‐affinity state is preferentially recognized by agonists in vitro. For this reason, agonist tracers have been developed as tools for the noninvasive imaging of the high‐affinity state with positron emission tomography (PET). This review provides an…