Neurocentre Magendie

Elke BINDER





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6 publication(s) depuis Septembre 2010:


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Les IF indiqués ont été collectés par le Web of Sciences en


25/07/2013 | Obesity (Silver Spring)   IF 3.4
Leucine supplementation modulates fuel substrates utilization and glucose metabolism in previously obese mice.
Binder E, Bermudez-Silva FJ, Elie M, Leste-Lasserre T, Belluomo I, Clark S, Duchampt A, Mithieux G, Cota D

Abstract:
OBJECTIVE: High-protein diets favor weight loss and its maintenance. Whether these effects might be recapitulated by certain amino acids is unknown. Therefore, the impact of leucine supplementation on energy balance and associated metabolic changes in diet-induced obese (DIO) mice during and after weight loss was investigated. DESIGN AND METHODS: DIO C57BL/6J mice were fed a normocaloric diet to induce weight loss while receiving or not the amino acid leucine in drinking water. Body weight, food intake, body composition, energy expenditure, glucose tolerance, insulin, and leptin sensitivity were evaluated. Q-PCR analysis was performed on muscle, brown and white adipose tissues. RESULTS: DIO mice decreased body weight and fat mass in response to chow, but supplementation with leucine did not affect these parameters. During weight maintenance, mice supplemented with leucine had improved glucose tolerance, increased leptin sensitivity, and lower respiratory quotient. The latter was associated with changes in the expression of several genes modulating fatty acid metabolism and mitochondrial activity in the epididymal white and the brown adipose tissues, but not muscle. CONCLUSIONS: Leucine supplementation might represent an adjuvant beneficial nutritional therapy during weight loss and maintenance, because it improves lipid and glucose metabolism and restores leptin sensitivity in previously obese animals.




19/03/2013 | Proc Natl Acad Sci U S A   IF 9.6
Activation of the sympathetic nervous system mediates hypophagic and anxiety-like effects of CB(1) receptor blockade.
Bellocchio L, Soria-Gomez E, Quarta C, Metna-Laurent M, Cardinal P, Binder E, Cannich A, Delamarre A, Haring M, Martin-Fontecha M, Vega D, Leste-Lasserre T, Bartsch D, Monory K, Lutz B, Chaouloff F, Pagotto U, Guzman M, Cota D, Marsicano G

Abstract:
Complex interactions between periphery and the brain regulate food intake in mammals. Cannabinoid type-1 (CB1) receptor antagonists are potent hypophagic agents, but the sites where this acute action is exerted and the underlying mechanisms are not fully elucidated. To dissect the mechanisms underlying the hypophagic effect of CB1 receptor blockade, we combined the acute injection of the CB1 receptor antagonist rimonabant with the use of conditional CB1-knockout mice, as well as with pharmacological modulation of different central and peripheral circuits. Fasting/refeeding experiments revealed that CB1 receptor signaling in many specific brain neurons is dispensable for the acute hypophagic effects of rimonabant. CB1 receptor antagonist-induced hypophagia was fully abolished by peripheral blockade of beta-adrenergic transmission, suggesting that this effect is mediated by increased activity of the sympathetic nervous system. Consistently, we found that rimonabant increases gastrointestinal metabolism via increased peripheral beta-adrenergic receptor signaling in peripheral organs, including the gastrointestinal tract. Blockade of both visceral afferents and glutamatergic transmission in the nucleus tractus solitarii abolished rimonabant-induced hypophagia. Importantly, these mechanisms were specifically triggered by lipid-deprivation, revealing a nutrient-specific component acutely regulated by CB1 receptor blockade. Finally, peripheral blockade of sympathetic neurotransmission also blunted central effects of CB1 receptor blockade, such as fear responses and anxiety-like behaviors. These data demonstrate that, independently of their site of origin, important effects of CB1 receptor blockade are expressed via activation of peripheral sympathetic activity. Thus, CB1 receptors modulate bidirectional circuits between the periphery and the brain to regulate feeding and other behaviors.




2013 | PLoS ONE   IF 3.1
Leucine supplementation protects from insulin resistance by regulating adiposity levels.
Binder E, Bermudez-Silva FJ, Andre C, Elie M, Romero-Zerbo SY, Leste-Lasserre T, Belluomo L, Duchampt A, Clark S, Aubert A, Mezzullo M, Fanelli F, Pagotto U, Laye S, Mithieux G, Cota D

Abstract:
BACKGROUND: Leucine supplementation might have therapeutic potential in preventing diet-induced obesity and improving insulin sensitivity. However, the underlying mechanisms are at present unclear. Additionally, it is unclear whether leucine supplementation might be equally efficacious once obesity has developed. METHODOLOGY/PRINCIPAL FINDINGS: Male C57BL/6J mice were fed chow or a high-fat diet (HFD), supplemented or not with leucine for 17 weeks. Another group of HFD-fed mice (HFD-pairfat group) was food restricted in order to reach an adiposity level comparable to that of HFD-Leu mice. Finally, a third group of mice was exposed to HFD for 12 weeks before being chronically supplemented with leucine. Leucine supplementation in HFD-fed mice decreased body weight and fat mass by increasing energy expenditure, fatty acid oxidation and locomotor activity in vivo. The decreased adiposity in HFD-Leu mice was associated with increased expression of uncoupling protein 3 (UCP-3) in the brown adipose tissue, better insulin sensitivity, increased intestinal gluconeogenesis and preservation of islets of Langerhans histomorphology and function. HFD-pairfat mice had a comparable improvement in insulin sensitivity, without changes in islets physiology or intestinal gluconeogenesis. Remarkably, both HFD-Leu and HFD-pairfat mice had decreased hepatic lipid content, which likely helped improve insulin sensitivity. In contrast, when leucine was supplemented to already obese animals, no changes in body weight, body composition or glucose metabolism were observed. CONCLUSIONS/SIGNIFICANCE: These findings suggest that leucine improves insulin sensitivity in HFD-fed mice by primarily decreasing adiposity, rather than directly acting on peripheral target organs. However, beneficial effects of leucine on intestinal gluconeogenesis and islets of Langerhans's physiology might help prevent type 2 diabetes development. Differently, metabolic benefit of leucine supplementation is lacking in already obese animals, a phenomenon possibly related to the extent of the obesity before starting the supplementation.




12/2011 | Pharmacogenet Genomics   IF 3.5
Antidepressants and the resilience to early-life stress in inbred mouse strains.
Binder E, Malki K, Paya-Cano JL, Fernandes C, Aitchison KJ, Mathe AA, Sluyter F, Schalkwyk LC

Abstract:
RATIONALE: Selecting an effective treatment for patients with major depressive disorder is a perpetual problem for psychiatrists. It is of particular interest to explore the interaction between genetic predisposition and environmental factors. OBJECTIVES: Mouse inbred strains vary in baseline performance in depression-related behaviour tests, which were originally validated as tests of antidepressant response. Therefore, we investigated interactions between environmental stress, genotype, and drug response in a multifactorial behaviour study. METHOD: Our study design included four inbred mouse strains (129S1/SvlmJ, C57LB/6J, DBA/2J and FVB/NJ) of both sexes, two subjected to environmental manipulations (maternal separation and unpredictable chronic mild stress) and two representative of treatment with antidepressants (escitalopram and nortryptiline vs. vehicle). The mice treated with antidepressants were further divided into those administered acute (1 day) and subchronic (14 days) regimes, giving 144 experimental groups in all, each with at least seven animals. All animals were tested using the Porsolt forced-swim test (FST) and the hole-board test. RESULTS: Despite a 24-h maternal separation (MS) or a 14-day unpredictable chronic mild stress protocol, most animals seemed to be resilient to the stress induced. One compelling finding is the long-lasting, strain-specific effect of MS resulting in an increased depression-like behaviour in the Porsolt FST and elevated anxiety-related behaviour in the hole-board test seen in 129S1/SvImJ mice. Nortriptyline was effective in reversing the effect of MS in the FST in 129S1/SvlmJ male mice. CONCLUSION: A single 24-h maternal separation of pups from their mother on postnatal day 9 is a sufficient insult to result in a depression-like phenotype in adult 129S1/SvImJ mice but not in C57LB/6 J, DBA/2 J, and FVB/NJ mice.




15/02/2011 | Biol Psychiatry   IF 8.9
Convergent animal and human evidence suggests a role of PPM1A gene in response to antidepressants
Malki K*, Uher R*, Paya-Cano J*, Binder E, Rietschel M, Zobel A, Mors O, Hauser J, Henigsberg N, Jerman B, Souery D, Placentino A, Nq MY, Cohen-Woods S, Sluyter F, Farmer A, Aitchison KJ, Craig IW, Lewis CM*, McGuffin P*, Schalkwyk LC*

Abstract:





28/09/2010 | Int J Obes (Lond)   IF 4.3
mTORC1 signaling in energy balance and metabolic disease.
Catania C, Binder E, Cota D

Abstract:
The mammalian target of rapamycin complex 1 (mTORC1) pathway regulates cellular