-
Mylène Vincent,
Erwann Philippe,
Amandine Everard,
Nadim Kassis,
Claude Rouch,
Jessica Denom,
Yorihiko Takeda,
Shoji Uchiyama,
Nathalie M Delzenne,
Patrice D Cani, Stéphanie Migrenne,
Christophe Magnan
[show abstract]
[hide abstract]
ABSTRACT: OBJECTIVE: Dietary supplement may potentially help to fight obesity and other metabolic disorders such as insulin-resistance and low-grade inflammation. The present study aimed to test whether supplementation with Agaricus blazei murill (ABM) extract could have an effect on diet-induced obesity in rats. DESIGN AND METHODS: Wistar rats were fed with control diet (CD) or high-fat diet (HF) and either with or without supplemented ABM for 20 weeks. RESULTS: HF diet-induced body weight gain and increased fat mass compared to CD. In addition HF-fed rats developed hyperleptinemia and insulinemia as well as insulin resistance and glucose intolerance. In HF-fed rats, visceral adipose tissue also expressed biomarkers of inflammation. ABM supplementation in HF rats had a protective effect against body weight gain and all study related disorders. This was not due to decreased food intake which remained significantly higher in HF rats whether supplemented with ABM or not compared to control. There was also no change in gut microbiota composition in HF supplemented with ABM. Interestingly, ABM supplementation induced an increase in both energy expenditure and locomotor activity which could partially explain its protective effect against diet-induced obesity. In addition a decrease in pancreatic lipase activity is also observed in jejunum of ABM-treated rats suggesting a decrease in lipid absorption. CONCLUSIONS: Taken together these data highlight a role for ABM to prevent body weight gain and related disorders in peripheral targets independently of effect in food intake in central nervous system.
Obesity 03/2013; 21(3):553-561. · 4.28 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Introduction: The hypothalamus plays a major role in the control of energy balance, by sensing circulating lipids. Several studies conducted over the past decade suggest that disruption of lipid sensing can lead to hypothalamic lipotoxicity, thereby contributing to the development of various diseases, such as obesity and type 2 diabetes. Areas covered: The physiological role of 'lipid sensing' as a regulator of neuronal activity involved in the regulation of energy homeostasis will be reviewed. Next, the emerging evidence that alterations of hypothalamic systems that regulate energy balance during overnutrition can lead to the development of obesity and associated pathologies such as type 2 diabetes will be described. Expert opinion: Several studies have highlighted the role of malonyl-CoA and PKCθ and also autophagy within the hypothalamus as signals of nutrient abundance by critical neurons regulating food intake. Besides the physiological role of hypothalamic lipid sensing, it has been shown that overnutrition can also induce hypothalamic lipotoxicity through an inflammatory process. In conclusion, lipid toxicity could be the starting point of perturbations of the central control of energy balance which will favor the appearance of obesity and type 2 diabetes. Lipid sensing in the hypothalamus could be considered as a potential target for anti-obesity/diabetic strategies.
Expert opinion on therapeutic targets 02/2013; · 3.72 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: It is currently admitted that Follicle-Stimulating Hormone (FSH) is physiologically involved in the development and function of fetal/neonatal Sertoli cells in the rat but not the mouse. However, FSH is produced by both species from late fetal life onwards. We thus reinvestigated the role of FSH in mouse testis development at day 0 (birth) 6, 8 and 10 post-partum (dpp) by using mice that lack functional FSH receptors (FSH-R(-/-)). At birth, the number and proliferative index of Sertoli cells were significantly lower in FSH-R(-/-) mice than in wild type neonates. Claudin 11 mRNA expression also was significantly reduced in FSH-R(-/-) testes at 0 and 8 dpp, whereas the mRNA levels of other Sertoli cell markers (Transferrin and Desert hedgehog) were comparable in FSH-R(-/-) and wild type testes. Conversely, AMH mRNA and protein levels were higher at birth, comparable at 6 dpp and then significantly lower in FSH-R(-/-) testes at 8-10 dpp in FSH-R(-/-) mice than in controls. Although the plasma concentration of LH and the number of Leydig cells were similar in FSH-R(-/-) and control (wild type), testosterone concentration and P450c17 mRNA expression were significantly increased in FSH-R(-/-) testes at birth. Conversely, at 10 dpp when adult Leydig cells appear, expression of the steroidogenic genes P450scc, P450c17 and StAR was lower in FSH-R(-/-) testes than in controls. In conclusion, our results show that 1) like in the rat, signaling via FSH-R controls Sertoli cell development and function during late fetal life in the mouse as well; 2) paracrine factors produced by Sertoli cells are involved in the FSH-R-dependent regulation of the functions of fetal Leydig cells in late fetal life; and 3) the role of FSH-R signaling changes during the prepubertal period.
PLoS ONE 01/2012; 7(12):e53257. · 4.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The activity of pituitary gonadotrope cells, crucial for reproductive function, is regulated by numerous factors including signals related to nutritional status. In this work, we demonstrated, for the first time, that in vivo central exposure of rats to lipids intracarotid infusion of a heparinized triglyceride emulsion selectively increases the expression of pituitary LH subunit genes without any alteration of pituitary GnRH receptor and hypothalamic GnRH or Kiss-1 transcript levels. Furthermore, we showed that unsaturated fatty acids (UFA), oleate and linoleate, increase LH release in a dose-dependent manner as well as LHβ mRNA levels in both immortalized LβT2 gonadotrope cell line and rat primary cell cultures. In contrast, the saturated palmitate was ineffective. ACTH or TSH secretion was unaffected by UFA treatment. We demonstrated in LβT2 cells that linoleate effect is mediated neither by activation of membrane fatty acid (FA) receptors GPR40 or GPR120 although we characterized these receptors in LβT2 cells, nor through nuclear peroxisome proliferator-activated receptors. Furthermore, linoleate β-oxidation is not required for its action on LH secretion. In contrast, pharmacological inhibition of protein kinase C (PKC) or ERK pathways significantly prevented linoleate-stimulated LH release. Accordingly, linoleate was shown to activate novel PKC isoforms, PKCε and -θ, as well as ERK1/2 in LβT2 cells. Lastly, unsaturated, but not saturated, FA inhibited GnRH-induced LH secretion in LβT2 cells as well as in pituitary cell cultures. Altogether, these results suggest that the pituitary is a relevant site of FA action and that UFA may influence reproduction by directly interfering with basal and GnRH-dependent gonadotrope activity.
Endocrinology 08/2011; 152(10):3905-16. · 4.46 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The increase in adiponectin levels in obese patients with untreated dyslipidemia and its mRNA expression in adipose tissue of obese animals are one of the most interesting consequences of rimonabant treatment. Thus, part of rimonabant's metabolic effects could be related to an enhancement of adiponectin secretion and its consequence on the modulation of insulin action, as well as energy homeostasis. The present study investigated the effects of rimonabant in adiponectin knockout mice (Ad(-/-)) exposed to diet-induced obesity conditions. Six-week-old Ad(-/-) male mice and their wild-type littermate controls (Ad(+/+)) were fed a high-fat diet for 7 mo. During the last month, animals were administered daily either with vehicle or rimonabant by mouth (10 mg/kg). High-fat feeding induced weight gain by about 130% in both wild-type and Ad(-/-) mice. Obesity was associated with hyperinsulinemia and insulin resistance. Treatment with rimonabant led to a significant and similar decrease in body weight in both Ad(+/+) and Ad(-/-) mice compared with vehicle-treated animals. In addition, rimonabant significantly improved insulin sensitivity in Ad(+/+) mice compared with Ad(+/+) vehicle-treated mice by decreasing hepatic glucose production and increasing glucose utilization index in both visceral and subcutaneous adipose tissue. In contrast, rimonabant failed to improve insulin sensitivity in Ad(-/-) mice, despite the loss in body weight. Rimonabant's effect on body weight appeared independent of the adiponectin pathway, whereas adiponectin seems required to mediate rimonabant-induced improvement of insulin sensitivity in rodents.
AJP Regulatory Integrative and Comparative Physiology 03/2009; 296(4):R929-35. · 3.34 Impact Factor
-
Stephanie Troy,
Maud Soty,
Lara Ribeiro,
Laure Laval, Stéphanie Migrenne,
Xavier Fioramonti,
Bruno Pillot,
Veronique Fauveau,
Roberte Aubert,
Benoit Viollet,
Marc Foretz,
Jocelyne Leclerc,
Adeline Duchampt,
Carine Zitoun,
Bernard Thorens,
Christophe Magnan,
Gilles Mithieux,
Fabrizio Andreelli
[show abstract]
[hide abstract]
ABSTRACT: Unlike the adjustable gastric banding procedure (AGB), Roux-en-Y gastric bypass surgery (RYGBP) in humans has an intriguing effect: a rapid and substantial control of type 2 diabetes mellitus (T2DM). We performed gastric lap-band (GLB) and entero-gastro anastomosis (EGA) procedures in C57Bl6 mice that were fed a high-fat diet. The EGA procedure specifically reduced food intake and increased insulin sensitivity as measured by endogenous glucose production. Intestinal gluconeogenesis increased after the EGA procedure, but not after gastric banding. All EGA effects were abolished in GLUT-2 knockout mice and in mice with portal vein denervation. We thus provide mechanistic evidence that the beneficial effects of the EGA procedure on food intake and glucose homeostasis involve intestinal gluconeogenesis and its detection via a GLUT-2 and hepatoportal sensor pathway.
Cell metabolism 10/2008; 8(3):201-11. · 17.35 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Adult mammals finely match glucose production to glucose utilization, thus allowing glycaemia to be maintained in a physiological range of 0.8-1.2mg/dl whatever the energetic status of the mammal (i.e. fed or fasted, rested or exercised). To accomplish this, peripheral signals originating from the gut 'inform' the central nervous system, which in turn is able to monitor the status of both peripheral glucose stores and ongoing fuel availability. Indeed, both secretion and action of hormones regulating endogenous glucose production and utilization are regulated by the autonomic nervous system. These gut signals are either hormonal (e.g. glucagon-like peptide-1, ghrelin and cholecystokinine) or neuronal (e.g. afferent vagus nerve fibres). Recent data, combined with the development of incretin analogues for treatment of diabetes, highlight the importance of the gut-brain axis, especially glucagon-like peptide-1 and ghrelin, in the control of glucose homeostasis.
Current Opinion in Pharmacology 01/2007; 6(6):592-7. · 6.86 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Although the role of pituitary hormones in fetal Sertoli cell proliferation is well understood, their involvement in fetal Sertoli cell differentiation is poorly documented. In this study, we evaluated rat fetal Sertoli cell function by measuring basal transferrin secretion ex vivo and transferrin and anti-Müllerian hormone (AMH) mRNA levels in vivo. The differentiation state of the Sertoli cells was estimated from the amount of transferrin secreted ex vivo after acute stimulation with FSH. Surprisingly, we found that the amount of transferrin secreted by each Sertoli cell in basal condition and after acute FSH stimulation decreased between 18.5 and 21.5 day post coitum (dpc), which corresponds to the onset of pituitary hormone secretion. All of the Sertoli cell parameters measured (basal and FSH-stimulated transferrin secretion ex vivo, transferrin and AMH mRNA levels in vivo) were higher in 21.5-dpc fetuses that had been decapitated on 16.5 dpc than in control littermates. Furthermore, immunostaining for AMH was strongly increased after decapitation. Taken together, these results suggest that pituitary hormones in the fetus and in the immature or adult rat differently regulate Sertoli cells, which suggests that fetal Sertoli cells have their own particular physiology.
Endocrinology 07/2003; 144(6):2617-22. · 4.46 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Addition of 5×10−2 U/ml recombinant luteinizing hormone (LH) to testes from fetuses at 16.5 day post conception (dpc) cultured for 5 days increased the number of Leydig cells by 34% and the acute LH-stimulated testosterone production by 600%. To determine whether these positive effects of LH in vitro are physiologically relevant in vivo, fetuses were decapitated on days 16.5 pc (before the onset of LH expression in the hypophysis) or 18.5 pc (before the surge of LH in the fetal plasma) and removed at 21.5 dpc. The number of fetal Leydig cells per testis and the acute LH-stimulated testosterone production by the testes ex vivo were unaltered by decapitation. Since, in all groups, the number of Leydig cells doubled between 16.5 and 18.5 dpc and between 18.5 and 21.5 dpc, these results suggest that neither the appearance of new fully differentiated fetal Leydig cells nor the maintenance of differentiated functions in existing fetal Leydig cells depend on LH during late fetal life, although this hormone is present in the plasma. Decapitation reduced the testosterone concentrations in the plasma (−56%) and in the testis in vivo (−67%) and the basal testosterone secretion of the testis ex vivo (−70%). This suggests that LH is required to maintain the physiological activity of the Leydig cell during late fetal life. However, the decrease of the in vivo testosterone production after decapitation was not sufficient to impair the growth of the Wolffian ducts and the lengthening of the anogenital distance. In conclusion, during late fetal life in the rat, Leydig cells are LH-independent for their functional differentiation and LH-dependent for their activity.
Molecular and Cellular Endocrinology 03/2001; · 4.19 Impact Factor
