Une alimentation maternelle enrichie en gras pendant la gestation et l’allaitement oriente le nouveau-né vers un lait produit sous régime gras (modèle murin)

Cyclo-oxygenase isoenzymes. How recent findings affect thinking about nonsteroidal anti-inflammatory drugs

International audience; The discovery of at least 2 cyclo-oxygenase (COX) isoenzymes, referred to as COX-1 and COX-2, has updated our knowledge of nonsteroidal anti-inflammatory drugs (NSAIDs). This has lead investigators to reconsider what can be awaited from this class of drugs. The 2 COX isoenzymes share structural and enzymatic similarities, but are specifically regulated at the molecular level and may be distinguished apart in their functions, although some physiological overlap between them does occur. The major goal in developing selective COX inhibitors is to improve NSAID tolerability. Classic NSAIDs preferentially inhibit COX-1 in vitro, but it appears hazardous to judge their gas…

The neuropeptide 26RFa (QRFP) is a key regulator of glucose homeostasis and its activity is markedly altered in obese/hyperglycemic mice

International audience; Recent studies have shown that the hypothalamic neuropeptide 26RFa regulates glucose homeostasis by acting as an incretin, and increasing insulin sensitivity. In this study, we further characterized the role of the 26RFa/GPR103 peptidergic system in the global regulation of glucose homeostasis using a 26RFa receptor antagonist, and also assessed whether a dysfunction of the 26RFa/GPR103 system occurs in obese hyperglycemic mice. Firstly, we demonstrate that administration of the GPR103 antagonist reduces the global glucose-induced incretin effect and insulin sensitivity whereas, conversely, administration of exogenous 26RFa attenuates glucose-induced hyperglycemia. U…

The histone acetyltransferase MOF activates hypothalamic polysialylation to prevent diet-induced obesity in mice

Overfeeding causes rapid synaptic remodeling in hypothalamus feeding circuits. Polysialylation of cell surface molecules is a key step in this neuronal rewiring and allows normalization of food intake. Here we examined the role of hypothalamic polysialylation in the long-term maintenance of body weight, and deciphered the molecular sequence underlying its nutritional regulation. We found that upon high fat diet (HFD), reduced hypothalamic polysialylation exacerbated the diet-induced obese phenotype in mice. Upon HFD, the histone acetyltransferase MOF was rapidly recruited on the St8sia4 polysialyltransferase-encoding gene. Mof silencing in the mediobasal hypothalamus of adult mice prevented…

The neuropeptide 26RFa in the human gut and pancreas: potential involvement in glucose homeostasis

Objective Recent studies performed in mice revealed that the neuropeptide 26RFa regulates glucose homeostasis by acting as an incretin and by increasing insulin sensitivity. However, in humans, an association between 26RFa and the regulation of glucose homeostasis is poorly documented. In this study, we have thus investigated in detail the distribution of 26RFa and its receptor, GPR103, in the gut and the pancreas, and determined the response of this peptidergic system to an oral glucose challenge in obese patients. Design and methods Distribution of 26RFa and GPR103 was examined by immunohistochemistry using gut and pancreas tissue sections. Circulating 26RFa was determined using a specif…

Importance of mitochondrial dynamin-related protein 1 in hypothalamic glucose sensitivity in rats.

International audience; AIMS: Hypothalamic mitochondrial reactive oxygen species (mROS)-mediated signaling has been recently shown to be involved in the regulation of energy homeostasis. However, the upstream signals that control this mechanism have not yet been determined. Here, we hypothesize that glucose-induced mitochondrial fission plays a significant role in mROS-dependent hypothalamic glucose sensing. RESULTS: Glucose-triggered translocation of the fission protein dynamin-related protein 1 (DRP1) to mitochondria was first investigated in vivo in hypothalamus. Thus, we show that intracarotid glucose injection induces the recruitment of DRP1 to VMH mitochondria in vivo. Then, expressio…

Food Intake Adaptation to Dietary Fat Involves PSA-Dependent Rewiring of the Arcuate Melanocortin System in Mice

International audience; Hormones such as leptin and ghrelin can rapidly rewire hypothalamic feeding circuits when injected into rodent brains. These experimental manipulations suggest that the hypothalamus might reorganize continually in adulthood to integrate the metabolic status of the whole body. In this study, we examined whether hypothalamic plasticity occurs in naive animals according to their nutritional conditions. For this purpose, we fed mice with a short-term high-fat diet (HFD) and assessed brain remodeling through its molecular and functional signature. We found that HFD for 3 d rewired the hypothalamic arcuate nucleus, increasing the anorexigenic tone due to activated pro-opio…

Une alimentation maternelle enrichie en gras pendant la gestation ou l’allaitement oriente les préférences du souriceau vers un aliment gras à la naissance et au sevrage

Transient Receptor Potential Canonical 3 (TRPC3) Channels Are Required for Hypothalamic Glucose Detection and Energy Homeostasis

Fil: Chrétien, Chloé. University of Bourgogne Franche-Comté. Institut National de la Recherche Agronomique. Centre des Sciences du Goût et de l’Alimentation; France Fil: Fenech, Claire. University of Bourgogne Franche-Comté. Institut National de la Recherche Agronomique. Centre des Sciences du Goût et de l’Alimentation; France Fil: Liénard, Fabienne. University of Bourgogne Franche-Comté. Institut National de la Recherche Agronomique. Centre des Sciences du Goût et de l’Alimentation; France Fil: Grall, Sylvie. University of Bourgogne Franche-Comté. Institut National de la Recherche Agronomique. Centre des Sciences du Goût et de l’Alimentation; France Fil: Chevalier, Charlène. University of …

Inactivation of Socs3 in the Hypothalamus Enhances the Hindbrain Response to Endogenous Satiety Signals via Oxytocin Signaling.

Leptin is an adipocyte-derived hormone that controls energy balance by acting primarily in the CNS, but its action is lost in common forms of obesity due to central leptin resistance. One potential mechanism for such leptin resistance is an increased hypothalamic expression of Suppressor of cytokine signaling 3 (Socs3), a feedback inhibitor of the Jak-Stat pathway that prevents Stat3 activation. Ample studies have confirmed the important role of Socs3 in leptin resistance and obesity. However, the degree to which Socs3 participates in the regulation of energy homeostasis in nonobese conditions remains largely undetermined. In this study, using adult mice maintained under standard diet, we d…

Brain Control of Plasma Cholesterol Involves Polysialic Acid Molecules in the Hypothalamus

IF 3.566; International audience; The polysialic acid (PSA) is a large glycan that is added to cell-surface proteins during their post-translational maturation. In the brain, PSA modulates distances between cells and controls the plasticity of the nervous system. In the hypothalamus, PSA is involved in many aspects of energy balance including food intake, osmoregulation, circadian rhythm, and sleep. In this work, we investigated the role of hypothalamic PSA in the regulation of plasma cholesterol levels and distribution. We report that HFD consumption in mice rapidly increased plasma cholesterol, including VLDL, LDL, and HDL-cholesterol. Although plasma VLDL-cholesterol was normalized withi…

Hypothalamus-specific deletion of socs3 in adult mice enhances hindbrain sensitivity to endogenous satiety signals via oxytocin signaling

Communication sans actes n° 469 (1 page) ; http://www.neurosciences.asso.fr/V2/colloques/SN11/; Leptin is a major contributor to long-term energy homeostasis, through an intracellular transduction pathway involving activation of Stat3 and its feedback inhibitor Socs3, which limits Stat3 activation. Previous studies have shown that Socs3 haploinsufficiency or socs3 deletion in the whole brain or in selective neuronal populations triggers an increased sensitivity to exogenous leptin, through increased Stat3 activation, and protects against diet-induced obesity in mice fed a high fat diet. Intriguingly however, no phenotype was detected when Socs3 mutant mice were maintained under standard die…

Lack of Hypothalamus Polysialylation Inducibility Correlates With Maladaptive Eating Behaviors and Predisposition to Obesity

This original research article (6 p.) is part of the research topic . Specialty section: This article was submitted to Neuroenergetics, Nutrition and Brain Health, a section of the journal Frontiers in Nutrition.; International audience; High variability exists in individual susceptibility to develop overweight in an obesogenic environment and the biological underpinnings of this heterogeneity are poorly understood. In this brief report, we show in mice that the vulnerability to diet-induced obesity is associated with low level of polysialic acid-neural cell adhesion molecule (PSA-NCAM), a factor of neural plasticity, in the hypothalamus. As we previously shown that reduction of hypothalami…