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December 2013 - September 2015
October 2009 - October 2013
Publications
Publications (52)
Human ageing, along with the ageing of conventional model organisms, is depicted as a continuous and progressive decline of biological capabilities accompanied by an exponentially increasing mortality risk. However, not all organisms experience ageing identically and our understanding of the phenomenon is coloured by human-centric views. Ageing is...
Ageing is characterised at the molecular level by six transcriptional ‘hallmarks of ageing’, that are commonly described as progressively affected as time passes. By contrast, the ‘Smurf’ assay separates high‐and‐constant‐mortality risk individuals from healthy, zero‐mortality risk individuals, based on increased intestinal permeability. Performing...
Since being described in Drosophila melanogaster in 2011, the Smurf phenotype, has been seen to be evolutionarily conserved in nematode and zebrafish, and has helped to identify the discontinuous nature of ageing and predict impending death from natural causes as well as from environmental stresses. This phenotype allowed us to model ageing as bein...
Aims:
Although prebiotics, probiotics, and fecal transplantation can alter the sensation of hunger and/or feeding behavior, the role of the constitutive gut microbiota in the short-term regulation of food intake during normal physiology is still unclear.
Results:
An antibiotic-induced microbiota depletion study was designed to compare feeding be...
In humans, obesity is associated with brain inflammation, glial reactivity, and immune cells infiltration. Studies in rodents have shown that glial reactivity occurs within 24 hr of high‐fat diet (HFD) consumption, long before obesity development, and takes place mainly in the hypothalamus (HT), a crucial brain structure for controlling body weight...
Mechanistic studies in rodents evidenced synaptic remodeling in neuronal circuits that control food intake. However, the physiological relevance of this process is not well defined. Here, we show that the firing activity of anorexigenic POMC neurons located in the hypothalamus is increased after a standard meal. Postprandial hyperactivity of POMC n...
In humans, obesity was associated with brain inflammation and glial cell proliferation. Studies in rodents showed that glial cell proliferation occurs within 24 hours of high-fat diet (HFD) consumption, before obesity development. This proliferation was mainly observed in the hypothalamus (HT), a crucial brain structure for controlling body weight....
To meet the challenge to human health posed by obesity, a better understanding of the regulation of feeding is essential. Medications targeting 5-hydroxytryptamine (5-HT; serotonin) 2C receptors (htr2c; 5-HT2CR) improve obesity. Here we probed the functional significance of 5-HT2CRs specifically within the brainstem nucleus of the solitary tract (5...
The hypothalamus is a key brain region in the regulation of energy balance as it controls food intake and both energy storage and expenditure through integration of humoral, neural, and nutrient-related signals and cues. Many years of research have focused on the regulation of energy balance by hypothalamic neurons, but the most recent findings sug...
Le surpoids et l’obésité représentent le cinquième facteur de risque mondial de décès (estimation de 2008, Organisation mondiale de la santé [OMS]). Dans la plupart des cas, l’obésité est due à une dérégulation de la balance énergétique qui est l’équilibre entre les entrées et les sorties d’énergie. Un des éléments majeurs dans la régulation de cet...
Sickness behavior defines the endocrine, autonomic, behavioral, and metabolic responses associated with infection. While inflammatory responses were suggested to be instrumental in the loss of appetite and body weight, the molecular underpinning remains unknown. Here, we show that systemic or central lipopolysaccharide (LPS) injection results in sp...
Food palatability and neuronal circuit
Document S1. Supplemental Experimental Procedures, Figures S1–S6, and Tables S1–S3 and S5
The reinforcing and motivational aspects of food are tied to the release of the dopamine in the mesolimbic system (ML). Free fatty acids from triglyceride (TG)-rich particles are released upon action of TG-lipases found at high levels in peripheral oxidative tissue (muscle, heart), but also in the ML. This suggests that local TG-hydrolysis in the M...
Objective:
Obesity is one of the primary healthcare challenges of the 21st century. Signals relaying information regarding energy needs are integrated within the brain to influence body weight. Central among these integration nodes are the brain pro-opiomelanocortin (POMC) peptides, perturbations of which disrupt energy balance and promote severe...
Feeding behavior is exquisitely regulated by homeostatic and hedonic neural substrates that integrate energy demand as well as the reinforcing and rewarding aspects of food. Understanding the net contribution of homeostatic and reward-driven feeding has become critical because of the ubiquitous source of energy-dense foods and the consequent obesit...
In both developed and emerging countries, sedentary life style and over exposition to high energy dense foods has led to a thermodynamic imbalance and consequently obesity. Obesity often involves a behavioural component in which, similar to drugs of abuse, compulsive consumption of palatable food rich in lipids and sugar drives energy intake far be...
In both developed and emerging countries, sedentary life style and over exposition to high energy dense foods has led to a thermodynamic imbalance and consequently obesity. Despite genetic predisposition, obesity often involves a behavioral component in which, similar to drugs of abuse, compulsive consumption of palatable food rich in lipids and su...
Fatty acid sensitive neurons located in hypothalamus, hippocampus or striatum are able to detect daily variations of plasma fatty acid levels. Thus, these neurons play a role to regulate energy balance by controling food intake, insulin secretion or hepatic glucose production. Molecular mechanisms that mediate fatty acid effects include receptor FA...
Fatty acid (FA)-sensitive neurons are present in the brain, especially the hypothalamus, and play a key role in the neural control of energy homeostasis. Through neuronal output, FA may modulate feeding behaviour as well as insulin secretion and action. Subpopulations of neurons in the ventromedial and arcuate hypothalamic nuclei are selectively ei...
Fatty acid (FA)-sensitive neurons are present in the brain, especially the hypothalamus, and play a key role in the neural control of energy
homeostasis. Through neuronal output, FA may modulate feeding behaviour as well as insulin secretion and action. Subpopulations of neurons
in the ventromedial and arcuate hypothalamic nuclei are selectively ei...
Circulating triglycerides (TGs) normally increase after a meal but are altered in pathophysiological conditions, such as obesity. Although TG metabolism in the brain remains poorly understood, several brain structures express enzymes that process TG-enriched particles, including mesolimbic structures. For this reason, and because consumption of hig...
The modern abundance of energy-rich foods combined with a shift to more sedentary lifestyles has led to a thermodynamic imbalance in which excessive caloric intake and reduced energy expenditure account for the prevalence of obesity. In particular, exposure to lipid-rich diet is thought to promote metabolic alteration in peripheral tissue associate...
The meso-cortico-limbic system, via dopamine release, encodes the rewarding and reinforcing properties of natural rewards. It is also activated in response to abused substances and is believed to support drug-related behaviors. Dysfunctions of this system lead to several psychiatric conditions including feeding disorders and drug addiction. These d...
Energy homoeostasis is maintained through a complex interplay of nutrient intake and energy expenditure. The central nervous system is an essential component of this regulation, as it integrates circulating signals of hunger and satiety to develop adaptive responses at the behavioural and metabolic levels, while the hypothalamus is regarded as a pa...
The modern abundance of energy-rich foods combined with a shift to more sedentary lifestyles has led to a thermodynamic imbalance in which excessive caloric intake and reduced energy expenditure account for the prevalence of obesity. In particular, exposure to lipid-rich diet is thought to promote metabolic alteration in peripheral tissue associate...
Several billion years of evolution were needed to create an adaptive mechanism to insure the proper energy intake required for the survival of any organism. A plethora of hormonal and nervous signals are integrated at the level of the hypothalamus and the brainstem and participate to the regulation of energy homeostasis. The motivational and hedoni...
The arcuate nucleus of the hypothalamus contains at least two populations of neurons that continuously monitor signals reflecting energy status and promote the appropriate behavioral and metabolic responses to changes in energy demand. Activation of neurons making pro-opiomelanocortin (POMC) decreases food intake and increases energy expenditure th...
Lipids are essential components of a living organism as energy source but also as constituent of the membrane lipid bilayer. In addition fatty acid (FA) derivatives interact with many signaling pathways. FAs have amphipathic properties and therefore require being associated to protein for both transport and intracellular trafficking. Here we will f...
Obesity-related diseases such as diabetes and dyslipidemia result from metabolic alterations including the defective conversion, storage and utilization of nutrients, but the central mechanisms that regulate this process of nutrient partitioning remain elusive. As positive regulators of feeding behaviour, agouti-related protein (AgRP) producing neu...
Laforin is a dual specificity protein phosphatase involved in Lafora disease (LD), a fatal form of progressive myoclonus epilepsy
characterized by neurodegeneration and the presence of intracellular polyglucosan inclusions (Lafora bodies) in different
tissues. In this work, we describe that mice lacking laforin (epm2a−/−) have enhanced insulin resp...
IntroductionL’intégration de signaux périphériques de faim et de satiété au niveau du système nerveux central permet de développer une réponse adaptée aux modifications de la disponibilité en nutriments. Les neurones oréxigènes à Neuropeptide Y et agouti-related protein (NPY/AgRP) et les neurones anoréxigènes à pro-opiomélanocortine (POMC) sont con...
Introduction
Le syndrome métabolique (Smet) est caractérisé par des facteurs de risque comme l’obésité abdominale ou la résistance à l’insuline… Plusieurs études suggèrent que les lipides nutritionnels seraient détectés par le système nerveux central (SNC) et participeraient au contrôle de la production de glucose et du comportement alimentaire. Un...
Introduction Le role des nutriments en tant que molecules informatives, ou « nutrient sensing », est fondamental pour le controle de l’homeostasie energetique, et toute modification des concentrations circulantes en nutriment est detectee au niveau du systeme nerveux central (SNC) par des neurones sensibles aux nutriments. Au cours d’un jeune de 24...