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Laurent gautron

Lin Jia, Xiuli Chang, Shuwen Qian, Chen Liu, Caleb C Lord, Newaz Ahmed, Charlotte E Lee, Syann Lee, Laurent Gautron, Mack C Mitchell, Jay D Horton, Philipp E Scherer, Joel K Elmquist
OBJECTIVE: Recent studies have suggested a critical role for toll-like receptor 4 (TLR4) in the development of alcoholic liver disease. As TLR4 is widely expressed throughout the body, it is unclear which TLR4-expressing cell types contribute to alcohol-induced liver damage. METHODS: We selectively ablated TLR4 in hepatocytes and myeloid cells. Male mice were fed a liquid diet containing either 5% alcohol or pair-fed a control diet for 4 weeks to examine chronic alcohol intake-induced liver damage and inflammation...
May 23, 2018: Molecular Metabolism
Yibing Wang, Liqin Cao, Chia-Ying Lee, Tomohiko Matsuo, Kejia Wu, Greg Asher, Lijun Tang, Tsuyoshi Saitoh, Jamie Russell, Daniela Klewe-Nebenius, Li Wang, Shingo Soya, Emi Hasegawa, Yoan Chérasse, Jiamin Zhou, Yuwenbin Li, Tao Wang, Xiaowei Zhan, Chika Miyoshi, Yoko Irukayama, Jie Cao, Julian P Meeks, Laurent Gautron, Zhiqiang Wang, Katsuyasu Sakurai, Hiromasa Funato, Takeshi Sakurai, Masashi Yanagisawa, Hiroshi Nagase, Reiko Kobayakawa, Ko Kobayakawa, Bruce Beutler, Qinghua Liu
Innate behaviors are genetically encoded, but their underlying molecular mechanisms remain largely unknown. Predator odor 2,4,5-trimethyl-3-thiazoline (TMT) and its potent analog 2-methyl-2-thiazoline (2MT) are believed to activate specific odorant receptors to elicit innate fear/defensive behaviors in naive mice. Here, we conduct a large-scale recessive genetics screen of ethylnitrosourea (ENU)-mutagenized mice. We find that loss of Trpa1, a pungency/irritancy receptor, diminishes TMT/2MT and snake skin-evoked innate fear/defensive responses...
May 23, 2018: Nature Communications
Kallia Apazoglou, Séverine Farley, Victor Gorgievski, Raoul Belzeaux, Juan Pablo Lopez, Julien Grenier, El Chérif Ibrahim, Marie-Anne El Khoury, Yiu C Tse, Raphaele Mongredien, Alexandre Barbé, Carlos E A de Macedo, Wojciech Jaworski, Ariane Bochereau, Alejandro Orrico, Elsa Isingrini, Chloé Guinaudie, Lenka Mikasova, Franck Louis, Sophie Gautron, Laurent Groc, Charbel Massaad, Ferah Yildirim, Vincent Vialou, Sylvie Dumas, Fabio Marti, Naguib Mechawar, Elise Morice, Tak P Wong, Jocelyne Caboche, Gustavo Turecki, Bruno Giros, Eleni T Tzavara
Depression, a devastating psychiatric disorder, is a leading cause of disability worldwide. Current antidepressants address specific symptoms of the disease, but there is vast room for improvement 1 . In this respect, new compounds that act beyond classical antidepressants to target signal transduction pathways governing synaptic plasticity and cellular resilience are highly warranted2-4 . The extracellular signal-regulated kinase (ERK) pathway is implicated in mood regulation5-7 , but its pleiotropic functions and lack of target specificity prohibit optimal drug development...
May 7, 2018: Nature Medicine
Kristoffer L Egerod, Natalia Petersen, Pascal N Timshel, Jens C Rekling, Yibing Wang, Qinghua Liu, Thue W Schwartz, Laurent Gautron
OBJECTIVES: G protein-coupled receptors (GPCRs) act as transmembrane molecular sensors of neurotransmitters, hormones, nutrients, and metabolites. Because unmyelinated vagal afferents richly innervate the gastrointestinal mucosa, gut-derived molecules may directly modulate the activity of vagal afferents through GPCRs. However, the types of GPCRs expressed in vagal afferents are largely unknown. Here, we determined the expression profile of all GPCRs expressed in vagal afferents of the mouse, with a special emphasis on those innervating the gastrointestinal tract...
June 2018: Molecular Metabolism
Alexandre Caron, Syann Lee, Joel K Elmquist, Laurent Gautron
Interactions between the brain and distinct adipose depots have a key role in maintaining energy balance, thereby promoting survival in response to metabolic challenges such as cold exposure and starvation. Recently, there has been renewed interest in the specific central neuronal circuits that regulate adipose depots. Here, we review anatomical, genetic and pharmacological studies on the neural regulation of adipose function, including lipolysis, non-shivering thermogenesis, browning and leptin secretion. In particular, we emphasize the role of leptin-sensitive neurons and the sympathetic nervous system in modulating the activity of brown, white and beige adipose tissues...
February 16, 2018: Nature Reviews. Neuroscience
Xuefeng Yuan, Alexandre Caron, Hua Wu, Laurent Gautron
Past studies have suggested that non-neuronal brain cells express the leptin receptor. However, the identity and distribution of these leptin receptor-expressing non-neuronal brain cells remain debated. This study assessed the distribution of the long form of the leptin receptor (LepRb) in non-neuronal brain cells using a reporter mouse model in which LepRb-expressing cells are permanently marked by tdTomato fluorescent protein (LepRb-CretdTomato ). Double immunohistochemistry revealed that, in agreement with the literature, the vast majority of tdTomato-tagged cells across the mouse brain were neurons (i...
2018: Frontiers in Neuroanatomy
Anne-Sophie Gautron, Alexandre Juillerat, Valérie Guyot, Jean-Marie Filhol, Emilie Dessez, Aymeric Duclert, Philippe Duchateau, Laurent Poirot
Using a TALEN-mediated gene-editing approach, we have previously described a process for the large-scale manufacturing of "off-the-shelf" CAR T cells from third-party donor T cells by disrupting the gene encoding TCRα constant chain (TRAC). Taking advantage of a previously described strategy to control TALEN targeting based on the exclusion capacities of non-conventional RVDs, we have developed highly efficient and specific nucleases targeting a key T cell immune checkpoint, PD-1, to improve engineered CAR T cells' functionalities...
December 15, 2017: Molecular Therapy. Nucleic Acids
Swalpa Udit, Michael Burton, Joseph M Rutkowski, Syann Lee, Angie L Bookout, Philipp E Scherer, Joel K Elmquist, Laurent Gautron
OBJECTIVE AND METHODS: Metabolic viscera and their vasculature are richly innervated by peripheral sensory neurons. Here, we examined the metabolic and inflammatory profiles of mice with selective ablation of all Nav 1.8-expressing primary afferent neurons. RESULTS: While mice lacking sensory neurons displayed no differences in body weight, food intake, energy expenditure, or body composition compared to controls on chow diet, ablated mice developed an exaggerated inflammatory response to high-fat feeding characterized by bouts of weight loss, splenomegaly, elevated circulating interleukin-6 and hepatic serum amyloid A expression...
October 2017: Molecular Metabolism
Bharath K Mani, Sherri Osborne-Lawrence, Mathieu Mequinion, Sydney Lawrence, Laurent Gautron, Zane B Andrews, Jeffrey M Zigman
OBJECTIVE: Ghrelin is a stomach-derived hormone that affects food intake and regulates blood glucose. The best-characterized actions of ghrelin are mediated by its binding to and activation of the growth hormone secretagogue receptor (GHSR; ghrelin receptor). Adequate examination of the identity, function, and relevance of specific subsets of GHSR-expressing neurons has been hampered by the absence of a suitable Cre recombinase (Cre)-expressing mouse line with which to manipulate gene expression in a targeted fashion within GHSR-expressing neurons...
August 2017: Molecular Metabolism
Xuefeng Yuan, Ying Huang, Sarita Shah, Hua Wu, Laurent Gautron
Cocaine- and amphetamine-regulated transcript (CART) is one of the most abundant neuropeptides in vagal afferents, including those involved in regulating feeding. Recent observations indicate that metabolic challenges dramatically alter the neuropeptidergic profile of CART-producing vagal afferents. Here, using confocal microscopy, we reassessed the distribution and regulation of CART(55-102) immunoreactivity in vagal afferents of the male mouse in response to metabolic challenges, including fasting and high-fat-diet feeding...
September 2016: ENeuro
Tengfei Jiang, Xueyan Li, Martine Bujoli-Doeuff, Eric Gautron, Laurent Cario, Stéphane Jobic, Romain Gautier
Optical and electrical characteristics of solid materials are well-known to be intimately related to the presence of intrinsic or extrinsic defects. Hence, the control of defects in semiconductors is of great importance to achieve specific properties, for example, transparency and conductivity. Herein, a facile and controllable reduction method for modulating the defects is proposed and used for the case of p-type delafossite CuCrO2 nanoparticles. The optical absorption in the infrared region of the CuCrO2 material can then be fine-tuned via the continuous reduction of nonstoichiometric Cu(II), naturally stabilized in small amounts...
August 1, 2016: Inorganic Chemistry
Yang Liu, Ying Huang, Tiemin Liu, Hua Wu, Huxing Cui, Laurent Gautron
Although Agouti-related peptide (AgRP) neurons play a key role in the regulation of food intake, their contribution to the anorexia caused by proinflammatory insults has yet to be identified. Using a combination of neuroanatomical and pharmacogenetics experiments, this study sought to investigate the importance of AgRP neurons and downstream targets in the anorexia caused by the peripheral administration of a moderate dose of lipopolysaccharide (LPS) (100 μg/kg, ip). First, in the C57/Bl6 mouse, we demonstrated that LPS induced c-fos in select AgRP-innervated brain sites involved in feeding but not in any arcuate proopiomelanocortin neurons...
June 2016: Endocrinology
Adèle Renaud, Laurent Cario, Xavier Rocquefelte, Philippe Deniard, Eric Gautron, Eric Faulques, Tilak Das, François Cheviré, Franck Tessier, Stéphane Jobic
No abstract text is available yet for this article.
September 30, 2015: Scientific Reports
Yang Liu, Ying Huang, Syann Lee, Angie L Bookout, Carlos M Castorena, Hua Wu, Laurent Gautron
Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-activated transcription factor that was originally identified as a regulator of peroxisome proliferation and adipocyte differentiation. Emerging evidence suggests that functional PPARγ signaling also occurs within the hypothalamus. However, the exact distribution and identities of PPARγ-expressing hypothalamic cells remains under debate. The present study systematically mapped PPARγ mRNA expression in the adult mouse brain using in situ hybridization histochemistry...
2015: Frontiers in Neuroanatomy
Laurent Gautron
No abstract text is available yet for this article.
October 2015: Endocrinology
Adèle Renaud, Laurent Cario, Xavier Rocquelfelte, Philippe Deniard, Eric Gautron, Eric Faulques, Tilak Das, François Cheviré, Franck Tessier, Stéphane Jobic
Owing to its high technological importance for optoelectronics, zinc oxide received much attention. In particular, the role of defects on its physical properties has been extensively studied as well as their thermodynamical stability. In particular, a large concentration of Zn vacancies in ZnO bulk materials is so far considered highly unstable. Here we report that the thermal decomposition of zinc peroxide produces wurtzite-type ZnO nanoparticles with an extraordinary large amount of zinc vacancies (>15%)...
September 3, 2015: Scientific Reports
Virginie Mansuy-Aubert, Laurent Gautron, Syann Lee, Angie L Bookout, Christine Kusminski, Kai Sun, Yuan Zhang, Philipp E Scherer, David J Mangelsdorf, Joel K Elmquist
Peripheral neural sensory mechanisms play a crucial role in metabolic regulation but less is known about the mechanisms underlying vagal sensing itself. Recently, we identified an enrichment of liver X receptor alpha and beta (LXRα/β) in the nodose ganglia of the vagus nerve. In this study, we show mice lacking LXRα/β in peripheral sensory neurons have increased energy expenditure and weight loss when fed a Western diet (WD). Our findings suggest that the ability to metabolize and sense cholesterol and/or fatty acids in peripheral neurons is an important requirement for physiological adaptations to WDs...
June 15, 2015: ELife
Laurent Gautron, Joel K Elmquist, Kevin W Williams
Recent insights into the neural circuits controlling energy balance and glucose homeostasis have rekindled the hope for development of novel treatments for obesity and diabetes. However, many therapies contribute relatively modest beneficial gains with accompanying side effects, and the mechanisms of action for other interventions remain undefined. This Review summarizes current knowledge linking the neural circuits regulating energy and glucose balance with current and potential pharmacotherapeutic and surgical interventions for the treatment of obesity and diabetes...
March 26, 2015: Cell
Alexander C Jackson, Chen Liu, Makoto Fukuda, Michael Lazarus, Laurent Gautron
No abstract text is available yet for this article.
2014: Frontiers in Neuroanatomy
Chen Liu, Angie L Bookout, Syann Lee, Kai Sun, Lin Jia, Charlotte Lee, Swalpa Udit, Yingfeng Deng, Philipp E Scherer, David J Mangelsdorf, Laurent Gautron, Joel K Elmquist
The vagus nerve innervates visceral organs providing a link between key metabolic cues and the CNS. However, it is not clear whether vagal neurons can directly respond to changing lipid levels and whether altered "lipid sensing" by the vagus nerve regulates energy balance. In this study, we systematically profiled the expression of all known nuclear receptors in laser-captured nodose ganglion (NG) neurons. In particular, we found PPARγ expression was reduced by high-fat-diet feeding. Deletion of PPARγ in Phox2b neurons promoted HFD-induced thermogenesis that involved the reprograming of white adipocyte into a brown-like adipocyte cell fate...
April 1, 2014: Cell Metabolism
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