Raphael DENIS's Publications List

Adipose tissue NAPE-PLD controls fat mass development by altering the browning process and gut microbiota.

2015-06-07T16:52:50Z

Obesity is a pandemic disease associated with many metabolic alterations and involves several organs and systems. The endocannabinoid system (ECS) appears to be a key regulator of energy homeostasis and metabolism. Here we show that specific deletion of the ECS synthesizing enzyme, NAPE-PLD, in adipocytes induces obesity, glucose intolerance, adipose tissue inflammation and altered lipid metabolis...

Lucie Geurts, Amandine Everard, Matthias Van Hul, Ahmed Essaghir, Thibaut Duparc, Sébastien Matamoros, Hubert Plovier, Julien Castel, Raphael G P Denis, Marie Bergiers, Céline Druart, Mireille Alhouayek, Nathalie M Delzenne, Giulio G Muccioli, Jean-Baptiste Demoulin, Serge Luquet, Patrice D Cani (2015) Nature communications 6:

Irf5 deficiency in macrophages promotes beneficial adipose tissue expansion and insulin sensitivity during obesity.

2015-06-07T16:52:50Z

Accumulation of visceral adipose tissue correlates with elevated inflammation and increased risk of metabolic diseases. However, little is known about the molecular mechanisms that control its pathological expansion. Transcription factor interferon regulatory factor 5 (IRF5) has been implicated in polarizing macrophages towards an inflammatory phenotype. Here we demonstrate that mice lacking Irf5,...

Elise Dalmas, Amine Toubal, Fawaz Alzaid, Katrina Blazek, Hayley L Eames, Kristell Lebozec, Maria Pini, Isabelle Hainault, Emilie Montastier, Raphaël G P Denis, Patricia Ancel, Amélie Lacombe, Yin Ling, Omran Allatif, Céline Cruciani-Guglielmacci, Sébastien André, Nathalie Viguerie, Christine Poitou, Vladimir Stich, Alexandra Torcivia, Fabienne Foufelle, Serge Luquet, Judith Aron-Wisnewsky, Dominique Langin, Karine Clément, Irina A Udalova, Nicolas Venteclef (2015) Nature medicine 21: 6 610-618

Hippocampal lipoprotein lipase regulates energy balance in rodents.

2015-06-07T16:52:50Z

Brain lipid sensing is necessary to regulate energy balance. Lipoprotein lipase (LPL) may play a role in this process. We tested if hippocampal LPL regulated energy homeostasis in rodents by specifically attenuating LPL activity in the hippocampus of rats and mice, either by infusing a pharmacological inhibitor (tyloxapol), or using a genetic approach (adeno-associated virus expressing Cre-GFP inj...

Alexandre Picard, Claude Rouch, Nadim Kassis, Valentine S Moullé, Sophie Croizier, Raphaël G Denis, Julien Castel, Nicolas Coant, Kathryn Davis, Deborah J Clegg, Stephen C Benoit, Vincent Prévot, Sébastien Bouret, Serge Luquet, Hervé Le Stunff, Céline Cruciani-Guglielmacci, Christophe Magnan (2014) Molecular metabolism 3: 2 167-176

Dietary triglycerides act on mesolimbic structures to regulate the rewarding and motivational aspects of feeding.

2015-06-07T16:52:50Z

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 high-fat diet alters dopamine signaling, we tested th...

C Cansell, J Castel, R G P Denis, C Rouch, A-S Delbes, S Martinez, D Mestivier, B Finan, J G Maldonado-Aviles, M Rijnsburger, M H Tschöp, R J DiLeone, R H Eckel, S E la Fleur, C Magnan, T S Hnasko, S Luquet (2014) Molecular psychiatry 19: 10 1095-1105

Intestinal epithelial MyD88 is a sensor switching host metabolism towards obesity according to nutritional status.

2015-06-07T16:52:50Z

Obesity is associated with a cluster of metabolic disorders, low-grade inflammation and altered gut microbiota. Whether host metabolism is controlled by intestinal innate immune system and the gut microbiota is unknown. Here we report that inducible intestinal epithelial cell-specific deletion of MyD88 partially protects against diet-induced obesity, diabetes and inflammation. This is associated w...

Amandine Everard, Lucie Geurts, Robert Caesar, Matthias Van Hul, Sébastien Matamoros, Thibaut Duparc, Raphael G P Denis, Perrine Cochez, Florian Pierard, Julien Castel, Laure B Bindels, Hubert Plovier, Sylvie Robine, Giulio G Muccioli, Jean-Christophe Renauld, Laure Dumoutier, Nathalie M Delzenne, Serge Luquet, Fredrik Bäckhed, Patrice D Cani (2014) Nature communications 5:

Intestinal deletion of leptin signaling alters activity of nutrient transporters and delayed the onset of obesity in mice.

2015-06-07T16:52:50Z

The importance of B-isoform of leptin receptor (LEPR-B) signaling in the hypothalamus, pancreas, or liver has been well characterized, but in the intestine, a unique site of entry for dietary nutrition into the body, it has been relatively ignored. To address this question, we characterized a mouse model deficient for LEPR-B specifically in intestinal epithelial cells (IECs). (IEC)LEPR-B-knockout ...

Annabelle Tavernier, Jean-Baptiste Cavin, Maude Le Gall, Robert Ducroc, Raphaël G P Denis, Françoise Cluzeaud, Sandra Guilmeau, Yassine Sakar, Laurence Barbot, Nathalie Kapel, Johanne Le Beyec, Francisca Joly, Streamson Chua, Serge Luquet, Andre Bado (2014) FASEB journal : official publication of the Federation of American Societies for Experimental Biology 28: 9 4100-4110

The hypothalamic arcuate nucleus and the control of peripheral substrates.

2015-06-07T16:52:50Z

The arcuate nucleus (ARC) of the hypothalamus is particularly regarded as a critical platform that integrates circulating signals of hunger and satiety reflecting energy stores and nutrient availability. Among ARC neurons, pro-opiomelanocortin (POMC) and agouti-related protein and neuropeptide Y (NPY/AgRP neurons) are considered as two opposing branches of the melanocortin signaling pathway. Integ...

Aurélie Joly-Amado, Céline Cansell, Raphaël G P Denis, Anne-Sophie Delbes, Julien Castel, Sarah Martinez, Serge Luquet (2014) Best practice & research. Clinical endocrinology & metabolism 28: 5 725-737

Central orchestration of peripheral nutrient partitioning and substrate utilization: implications for the metabolic syndrome.

2015-06-07T16:52:50Z

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 particularly crucial structure in the brain in terms...

R G P Denis, A Joly-Amado, C Cansell, J Castel, S Martinez, A S Delbes, S Luquet (2014) Diabetes & metabolism 40: 3 191-197

Beige differentiation of adipose depots in mice lacking prolactin receptor protects against high-fat-diet-induced obesity.

2014-04-15T13:34:31Z

Stimulating conversion of white fat to metabolically active adipocytes (beige fat) constitutes a promising strategy against weight gain and its deleterious associated-disorders. We provide direct evidence that prolactin (PRL), best known for its actions on the mammary gland, plays a pivotal role in energy balance through the control of adipocyte differentiation and fate. Here we show that lack of ...

Julien Auffret, Say Viengchareun, Nadège Carré, Raphaël G P Denis, Christophe Magnan, Pierre-Yves Marie, Adeline Muscat, Bruno Fève, Marc Lombès, Nadine Binart (2012) FASEB journal : official publication of the Federation of American Societies for Experimental Biology 26: 9 3728-3737

Arcuate AgRP neurons and the regulation of energy balance.

2015-06-07T16:52:50Z

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 through activation of G protein-coupled melanocortin...

Céline Cansell, Raphaël G P Denis, Aurélie Joly-Amado, Julien Castel, Serge Luquet (2012) Frontiers in endocrinology 3:

Hypothalamic AgRP-neurons control peripheral substrate utilization and nutrient partitioning.

2015-06-07T16:52:50Z

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 neurons are indispensible for the hypothalamic integr...

Aurélie Joly-Amado, Raphaël G P Denis, Julien Castel, Amélie Lacombe, Céline Cansell, Claude Rouch, Nadim Kassis, Julien Dairou, Patrice D Cani, Renée Ventura-Clapier, Alexandre Prola, Melissa Flamment, Fabienne Foufelle, Christophe Magnan, Serge Luquet (2012) The EMBO journal 31: 22 4276-4288

Laforin, a dual specificity phosphatase involved in Lafora disease, regulates insulin response and whole-body energy balance in mice.

2011-10-28T19:29:31Z

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 response leading to altered whole-body energy balance....

Santiago Vernia, Miguel Heredia, Olga Criado, Santiago Rodriguez de Cordoba, Pablo M Garcia-Roves, Céline Cansell, Raphael Denis, Serge Luquet, Fabienne Foufelle, Pascal Ferre, Pascual Sanz (2011) Hum Mol Genet 20: 13 2571-2584

Additive effects of olanzapine and melanin-concentrating hormone agonism on energy balance.

2014-04-15T13:34:31Z

Atypical antipsychotic drugs (AAPDs) induce hyperphagia and body weight gain as a deleterious side effect. However, the mechanism whereby these drugs affect the neuronal pathways regulating energy balance has yet to be fully elucidated. The present study was conducted to investigate the respective and interaction effects of olanzapine and agonism of the melanin-concentrating hormone (MCH) receptor...

Benjamin Guesdon, Raphaël G P Denis, Denis Richard (2010) Behavioural brain research 207: 1 14-20

TNF-α transiently induces endoplasmic reticulum stress and an incomplete unfolded protein response in the hypothalamus.

2014-04-15T13:34:31Z

In diet-induced obesity, hypothalamic inflammation is triggered as an outcome of prolonged exposure to dietary fats. Toll-like receptor 4 (TLR4) activation plays a central role in this process, inducing endoplasmic reticulum stress and activating inflammatory cytokine gene transcription. Although saturated fatty acids can induce endoplasmic reticulum stress in the hypothalamus, it is unknown wheth...

R G Denis, A P Arruda, T Romanatto, M Milanski, A Coope, C Solon, D S Razolli, L A Velloso (2010) Neuroscience 170: 4 1035-1044

The nutritional induction of COUP-TFII gene expression in ventromedial hypothalamic neurons is mediated by the melanocortin pathway.

2014-04-15T13:34:31Z

The nuclear receptor chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) is an important coordinator of glucose homeostasis. We report, for the first time, a unique differential regulation of its expression by the nutritional status in the mouse hypothalamus compared to peripheral tissues.

Lina Sabra-Makke, Cécile Tourrel-Cuzin, Raphaël G P Denis, Marthe Moldes, Jean-Paul Pégorier, Serge Luquet, Mireille Vasseur-Cognet, Pascale Bossard (2010) PloS one 5: 10

Saturated fatty acids produce an inflammatory response predominantly through the activation of TLR4 signaling in hypothalamus: implications for the pathogenesis of obesity.

2010-04-29T11:33:51Z

In animal models of diet-induced obesity, the activation of an inflammatory response in the hypothalamus produces molecular and functional resistance to the anorexigenic hormones insulin and leptin. The primary events triggered by dietary fats that ultimately lead to hypothalamic cytokine expression and inflammatory signaling are unknown. Here, we test the hypothesis that dietary fats act through ...

Marciane Milanski, Giovanna Degasperi, Andressa Coope, Joseane Morari, Raphael Denis, Dennys E Cintra, Daniela M L Tsukumo, Gabriel Anhe, Maria E Amaral, Hilton K Takahashi, Rui Curi, Helena C Oliveira, José B C Carvalheira, Silvana Bordin, Mário J Saad, Lício A Velloso (2009) J Neurosci 29: 2 359-370

Reactive oxygen species production is increased in the peripheral blood monocytes of obese patients.

2014-04-15T13:34:31Z

Infiltrating macrophages play an important role in the production of inflammatory mediators by the adipose tissue of obese subjects. To reach the adipose tissue, peripheral monocytes are recruited by locally produced chemoattractants. However, little is known about the activation of monocytes in the peripheral blood of obese subjects. The objective of this study was to determine reactive oxygen sp...

Giovanna R Degasperi, Raphael G P Denis, Joseane Morari, Carina Solon, Bruno Geloneze, Christiane Stabe, José Carlos Pareja, Aníbal E Vercesi, Lício A Velloso (2009) Metabolism: clinical and experimental 58: 8 1087-1095

Deletion of tumor necrosis factor-alpha receptor 1 (TNFR1) protects against diet-induced obesity by means of increased thermogenesis.

2014-04-15T13:34:31Z

In diet-induced obesity, hypothalamic and systemic inflammatory factors trigger intracellular mechanisms that lead to resistance to the main adipostatic hormones, leptin and insulin. Tumor necrosis factor-alpha (TNF-alpha) is one of the main inflammatory factors produced during this process and its mechanistic role as an inducer of leptin and insulin resistance has been widely investigated. Most o...

Talita Romanatto, Erika A Roman, Ana P Arruda, Raphael G Denis, Carina Solon, Marciane Milanski, Juliana C Moraes, Maria L Bonfleur, Giovanna R Degasperi, Paty K Picardi, Sandro Hirabara, Antonio C Boschero, Rui Curi, Licio A Velloso (2009) The Journal of biological chemistry 284: 52 36213-36222

Fyn mediates leptin actions in the thymus of rodents.

2014-04-15T13:34:31Z

Several effects of leptin in the immune system rely on its capacity to modulate cytokine expression and apoptosis in the thymus. Surprisingly, some of these effects are dependent on signal transduction through the IRS1/PI3-kinase, but not on the activation of JAK2. Since all the well known effects of leptin in different cell types and tissues seem to be dependent on JAK2 activation, we hypothesize...

Alessandra Girasol, Gabriela G Albuquerque, Eli Mansour, Eliana P Araújo, Giovanna Degasperi, Raphael G Denis, José B Carvalheira, Mário J Saad, Lício A Velloso (2009) PloS one 4: 11

Peroxisome proliferator-activated receptor-gamma-mediated positive energy balance in the rat is associated with reduced sympathetic drive to adipose tissues and thyroid status.

2014-04-15T13:34:31Z

Peroxisome proliferator-activated receptor-gamma (PPARgamma) activation up-regulates thermogenesis-related genes in rodent white and brown adipose tissues (WAT and BAT) without increasing whole-body energy expenditure. We tested here whether such dissociation is the result of a negative modulation of sympathetic activity to WAT and BAT and thyroid axis components by PPARgamma activation. Administr...

William T Festuccia, Serdar Oztezcan, Mathieu Laplante, Magalie Berthiaume, Chantal Michel, Shinya Dohgu, Raphaël G Denis, Marcia N Brito, Nilton A Brito, David S Miller, William A Banks, Timothy J Bartness, Denis Richard, Yves Deshaies (2008) Endocrinology 149: 5 2121-2130

UCP2 protects hypothalamic cells from TNF-alpha-induced damage.

2014-04-15T13:34:31Z

Uncoupling protein 2 (UCP2) is highly expressed in the hypothalamus; however, little is known about the functions it exerts in this part of the brain. Here, we hypothesized that UCP2 protects hypothalamic cells from oxidative and pro-apoptotic damage generated by inflammatory stimuli. Intracerebroventricular injection of tumor necrosis factor alpha (TNF-alpha)-induced an increase of UCP2 expressio...

Giovanna R Degasperi, Talita Romanatto, Raphael G P Denis, Eliana P Araújo, Juliana C Moraes, Natália M Inada, Aníbal E Vercesi, Lício A Velloso (2008) FEBS letters 582: 20 3103-3110

Effects of rimonabant (SR141716) on fasting-induced hypothalamic-pituitary-adrenal axis and neuronal activation in lean and obese Zucker rats.

2014-04-15T13:34:31Z

The effects of the cannabinoid-1 receptor (CB(1)) antagonist rimonabant on energy metabolism and fasting-induced hypothalamic-pituitary-adrenal (HPA) axis and neuronal activation were investigated. Lean and obese Zucker rats were treated orally with a daily dose of 10 mg/kg rimonabant for 14 days. A comprehensive energy balance profile based on whole-carcass analyses further demonstrated the poten...

Christian Doyon, Raphaël G Denis, Elena-Dana Baraboi, Pierre Samson, Josée Lalonde, Yves Deshaies, Denis Richard (2006) Diabetes 55: 12 3403-3410

Diurnal changes in hypothalamic neuropeptide and SOCS-3 expression: effects of lactation and relationship with serum leptin and food intake.

2014-04-15T13:34:31Z

Rats normally eat about 85% of their food at night. Lactation increases food intake 3- to 4-fold, but the diurnal pattern of food intake persists. The mechanisms responsible for the diurnal and lactation-induced changes in food intake are still unresolved, hence we have further investigated the possible roles of serum leptin and hypothalamic expression of neuropeptide Y (NPY), agouti-related pepti...

R G P Denis, C Bing, S Brocklehurst, J A Harrold, R G Vernon, G Williams (2004) The Journal of endocrinology 183: 1 173-181

Regulation of serum leptin and its role in the hyperphagia of lactation in the rat.

2014-04-15T13:34:31Z

The factors regulating serum leptin concentration and its relationship to the hyperphagia of lactation have been investigated in rats. Lactation results in hypoleptinaemia and loss, or at least marked attenuation, of the nocturnal rise in serum leptin. Litter removal resulted in a fall in food intake and restoration of the nocturnal rise in serum leptin. Returning the litter to the mother after a ...

R G P Denis, G Williams, R G Vernon (2003) The Journal of endocrinology 176: 2 193-203

Lactation modulates diurnal expression profiles of specific leptin receptor isoforms in the rat hypothalamus.

2014-04-15T13:34:31Z

We investigated the effects of lactation on diurnal changes in serum leptin and hypothalamic expression of the leptin receptor isoforms, Ob-Ra, -Rb, -Rc, -Re and -Rf in rats. In non-lactating rats, serum leptin concentration was increased at night while hypothalamic mRNA levels of Ob-Rb, -Rc and -Re decreased; by contrast, expression of Ob-Ra and Ob-Rf was unchanged at night. There were significan...

R G P Denis, C Bing, E K Naderali, R G Vernon, G Williams (2003) The Journal of endocrinology 178: 2 225-232

A fat-enriched, glucose-enriched diet markedly attenuates adiponectin mRNA levels in rat epididymal adipose tissue.

2014-04-15T13:34:31Z

Adiponectin levels are decreased in subjects with obesity, diabetes and coronary artery disease. In the present study, we have investigated whether the decrease in the levels and mRNA expression of adiponectin is due to obesity or to the diet itself. Wistar rats were either fed standard laboratory chow throughout (controls) or given a fat-enriched, glucose-enriched diet (diet-fed) for 2 days or 16...

Ebrahim K Naderali, Debora Estadella, Milagros Rocha, Lucy C Pickavance, Sameer Fatani, Raphael G P Denis, Gareth Williams (2003) Clinical science (London, England : 1979) 105: 4 403-408

Leptin and the adaptations of lactation in rodents and ruminants.

2014-04-15T13:34:31Z

Lactation markedly increases nutrient requirements in both rodents and ruminants. This is met mostly by increased food intake, but there are also adaptations to increase metabolic efficiency. Despite such changes, lactating animals usually experience periods of negative energy balance. This is not due to a physical constraint on food intake, at least in the rat. Leptin, a hormone secreted by adipo...

R G Vernon, R G P Denis, A Sorensen, G Williams (2002) Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et métabolisme 34: 11-12 678-685

Signals of adiposity.

2014-04-15T13:34:31Z

Adipose tissue, a reserve of energy, has played an essential role in mammalian evolution. Adipose tissue differs from other tissues in that its mass has considerable capacity to expand, which while beneficial in decreasing the risk of starvation, increases the risk of predation. Adipose tissue mass is thus under tight control in nondomestic species. Adipose tissue secretes a variety of factors, so...

R G Vernon, R G Denis, A Sørensen (2001) Domestic animal endocrinology 21: 4 197-214

Food restriction selectively increases hypothalamic orexin-B levels in lactating rats.

2010-04-29T11:36:16Z

Orexins are hypothalamic peptides implicated in the regulation of ingestive and other behaviours. Here we investigated prepro-orexin expression and hypothalamic orexin-A and -B levels in lactating rats, which display marked hyperphagia, with or without food restriction for 2 days or treatment with bromocriptine, which inhibits milk production and thus reduces the energy losses of lactation. Neithe...

X J Cai, R Denis, R G Vernon, J C Clapham, S Wilson, J R Arch, G Williams (2001) Regul Pept 97: 2-3 163-168

Acyltransferase activities in the yolk sac membrane of the chick embryo.

2010-04-29T11:36:16Z

The activities of some enzymes of glycerolipid synthesis and fatty acid oxidation were measured in subcellular fractions of the yolk sac membrane (YSM), an extra-embryonic tissue that mediates the transfer of lipid from the yolk to the circulation of the chick embryo. The activities of monoacylglycerol acyltransferase and carnitine palmitoyl transferase-1 in the YSM (respectively, 284.8+/-13.2 nmo...

A M Murray, R Denis, B K Speake (1999) Lipids 34: 9 929-935