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ABSTRACT: Perinatal leptin impairment has long term consequences on energy homeostasis leading to body weight gain. The underlying mechanisms are still not clearly established. We aimed to analyze the long term effects of early leptin blockade. In the present study, newborn rats received daily injection of a pegylated leptin antagonist (pRLA) or saline from day2 to day13, and then body weight gain, insulin/leptin sensitivity and expression profile of microRNAs (miRNAs) at the hypothalamic level determined at d28, d90 or d153 (following one month of high fat diet challenge). We show that pRLA treatment predisposes rats to overweight and promotes leptin/ insulin-resistance in both hypothalamus and liver at the adulthood. pRLA treatment also modifies hypothalamic miRNA expression profile at d28 leading to the up-regulation of 34 miRNAs and the down-regulation of 4 miRNAs. For quantitative RT-PCR confirmationwe show the up-regulation of miR-10a at d28, and miR-200a, miR-409-5p and miR-125a-3p following High Fat Diet (HFD) challenge. Finally, pRLA treatment modifies the expression of genes involved in energy homeostasis control such as UCPs and AdipoRs. In pRLA rat muscle, UCP2/3 and AdipoR1/R2 are up-regulated at day90. In liver, pRLA treatment up-regulateAdipoR1/R2 following HFD challenge. These genes are known to be involved in insulin resistance and type-2 diabetes. In conclusion, we demonstrate that the impairment of leptin action in early life promotes insulin/leptin-resistance and modifies hypothalamic miRNA expression pattern in the adulthood, and finally this study highlights the potential link between hypothalamic miRNA expression pattern and insulin/leptin responsiveness.
Journal of Endocrinology 04/2013; · 3.55 Impact Factor
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ABSTRACT: Resistin promotes both inflammation and insulin resistance associated with energy homeostasis impairment. However, the resistin receptor and the molecular mechanisms mediating its effects in the hypothalamus, crucial for energy homeostasis control, and key insulin-sensitive tissues are still unknown. In the current study, we report that chronic resistin infusion in the lateral cerebral ventricle of normal rats markedly affects both hypothalamic and peripheral insulin responsiveness. Central resistin treatment inhibited insulin-dependent phosphorylation of insulin receptor (IR), AKT, and extracellular signal-related kinase 1/2 associated with reduced IR expression and with upregulation of suppressor of cytokine signaling-3 and phosphotyrosine phosphatase 1B, two negative regulators of insulin signaling. Additionally, central resistin promotes the activation of the serine kinases Jun NH(2)-terminal kinase and p38 mitogen-activated protein kinase, enhances the serine phosphorylation of insulin receptor substrate-1, and increases the expression of the proinflammatory cytokine interleukin-6 in the hypothalamus and key peripheral insulin-sensitive tissues. Interestingly, we also report for the first time, to our knowledge, the direct binding of resistin to Toll-like receptor (TLR) 4 receptors in the hypothalamus, leading to the activation of the associated proinflammatory pathways. Taken together, our findings clearly identify TLR4 as the binding site for resistin in the hypothalamus and bring new insight into the molecular mechanisms involved in resistin-induced inflammation and insulin resistance in the whole animal.
Diabetes 09/2012; · 8.29 Impact Factor
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ABSTRACT: Serotonin and insulin are key regulators of homeostatic mechanisms in the hypothalamus. However, in type 2 diabetes, the hypothalamic responsiveness to serotonin is not clearly established. We used a dia-betic model, the Goto Kakizaki (GK) rats, to explore insulin receptor expression, insulin and serotonin efficiency in the hypothalamus and liver by means of Akt phosphorylation. Insulin or dexfenfluramine (stimulator of serotonin) treatment induced Akt phosphorylation in Wistar rats but not in GK rats that exhibit down-regulated insulin receptor. Studies in a neuroblastoma cell line showed that serotonin-induced Akt phosphorylation is PI3-kinase dependent. Finally, in response to food intake, hypothalamic serotonin release was reduced in GK rats, indicating impaired responsiveness of this neurotransmitter. In conclusion, hypothalamic serotonin as insulin efficiency is impaired in diabetic GK rats. The insulin– serotonin cross-talk and impairment observed is one potential key modification in the brain during the onset of diabetes.
Molecular and Cellular Endocrinology 03/2012; · 4.19 Impact Factor
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ABSTRACT: Ciliary neurotrophic factor (CNTF) is a neural cytokine that reduces appetite and body weight when administrated to rodents or humans. We have demonstrated recently that the level of CNTF in the arcuate nucleus (ARC), a key hypothalamic region involved in food intake regulation, is positively correlated with protection against diet-induced obesity. However, the comprehension of the physiological significance of neural CNTF action was still incomplete because CNTF lacks a signal peptide and thus may not be secreted by the classical exocytosis pathways. Knowing that CNTF distribution shares similarities with that of its receptor subunits in the rat ARC, we hypothesized that CNTF could exert a direct intracrine effect in ARC cells. Here, we demonstrate that CNTF, together with its receptor subunits, translocates to the cell nucleus of anorexigenic POMC neurons in the rat ARC. Furthermore, the stimulation of hypothalamic nuclear fractions with CNTF induces the phosphorylation of several signaling proteins, including Akt, as well as the transcription of the POMC gene. These data strongly suggest that intracellular CNTF may directly modulate POMC gene expression via the activation of receptors localized in the cell nucleus, providing a novel plausible mechanism of CNTF action in regulating energy homeostasis.
AJP Endocrinology and Metabolism 12/2011; 302(4):E458-67. · 4.75 Impact Factor
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ABSTRACT: Recent studies reported the impact of leptin on peripheral insulin sensitivity and glucose utilization. However, little is known concerning the effect of central leptin on hypothalamic and hepatic insulin efficiency. This study aimed to determine the consequence of chronic intra-cerebroventricular (ICV) leptin or murine leptin antagonist (MLA) infusion on hypothalamic and hepatic insulin signaling pathways, in rats. A 2-week central leptin infusion enhanced insulin-dependent Akt phosphorylation in the liver without changing PTP-1B protein expression, associated to insulin receptor (IR) upregulation and reduced IRS-1 phosphorylation on Ser302 residue. In the hypothalamus, a chronic ICV leptin infusion induced PTP-1B associated with a specific decrease in insulin-dependent Akt phosphorylation. In contrast, a chronic MLA infusion did not alter IR and PTP-1B expressions in hypothalamus and liver. Our results underline a brain leptin-dependent increase in hepatic insulin efficiency as mirrored by IR up-regulation, increased insulin-dependent Akt phosphorylation and reduced IRS-1 phosphorylation on Ser302 residue.
Molecular and Cellular Endocrinology 02/2011; 337(1-2):89-95. · 4.19 Impact Factor
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General and Comparative Endocrinology 02/2011; 171(3):267-8. · 3.27 Impact Factor
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ABSTRACT: Metabolic and endocrine environment during early life is crucial for metabolic imprinting. When dams were fed a high fat diet (HF diet), rat offspring developed hypothalamic leptin resistance with lean phenotype when weaned on a normal diet. Interestingly, when grown on the HF diet, they appeared to be protected against the effects of HF diet as compared to offspring of normally fed dams. The mechanisms involved in the protective effect of maternal HF diet are unclear.
We thus investigated the impact of maternal high fat diet on offspring subjected to normal or high palatable diet (P diet) on metabolic and endocrine parameters. We compared offspring born to dams fed P or HF diet. Offspring born to dams fed control or P diet, when fed P diet exhibited a higher body weight, altered hypothalamic leptin sensitivity and metabolic parameters suggesting that maternal P diet has no protective effect on offspring. Whereas, maternal HF diet reduces body weight gain and circulating triglycerides, and ameliorates corpulence index of offspring, even when subjected to P diet. Interestingly, this protective effect is differently expressed in male and female offspring. Male offspring exhibited higher energy expenditure as mirrored by increased hypothalamic UCP-2 and liver AdipoR1/R2 expression, and a profound change in the arcuate nucleus astrocytic organization. In female offspring, the most striking impact of maternal HF diet is the reduced hypothalamic expression of NPY and POMC.
HF diet given during gestation and lactation protects, at least partially, offspring from excessive weight gain through several mechanisms depending upon gender including changes in arcuate nucleus astrocytic organization and increased hypothalamic UCP-2 and liver AdipoR1/2 expression in males and reduced hypothalamic expression of NPY and POMC in females. Taken together our results reveal new mechanisms involved in the protective effect of maternal HF diet.
PLoS ONE 01/2011; 6(3):e18043. · 4.09 Impact Factor
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Caroline Rouas,
Helene Bensoussan,
David Suhard,
Christine Tessier,
Line Grandcolas,
François Rebiere,
Isabelle Dublineau, Mohammed Taouis,
Marc Pallardy,
Philippe Lestaevel,
Yann Gueguen
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ABSTRACT: Uranium is naturally found in the environment, and its extensive use results in an increased risk of human exposure. Kidney cells have mainly been used as in vitro models to study effects of uranium exposure, and very little about the effects on other cell types is known. The aim of this study was to assess the impact of depleted uranium exposure at the cellular level in human kidney (HEK-293), liver (HepG2), and neuronal (IMR-32) cell lines. Cytotoxicity studies showed that these cell lines reacted in a roughly similar manner to depleted uranium exposure, responding at a cytotoxicity threshold of 300-500 μM. Uranium was localized in cells with secondary ion mass spectrometry technology. Results showed that uranium precipitates at subtoxic concentrations (>100 μM). With this approach, we were able for the first time to observe the soluble form of uranium in the cell at low concentrations (10-100 μM). Moreover, this technique allows us to localize it mainly in the nucleus. These innovative results raise the question of how uranium penetrates into cells and open new perspectives for studying the mechanisms of uranium chemical toxicity.
Chemical Research in Toxicology 11/2010; 23(12):1883-9. · 3.78 Impact Factor
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Toxicology 01/2010; 267(1-3):182. · 3.68 Impact Factor
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ABSTRACT: Adiponectin regulates energy homeostasis through the modulation of glucose and fatty acid metabolism in peripheral tissues. However, its central effect on energy balance remains unclear and controversial. Despite the disparate data, recent advances in our understanding of the signal transduction mechanisms used by adiponectin in the periphery and in the hypothalamus suggest that intracellular cross-talk between adiponectin, leptin and insulin may occur at several levels. The present review will summarize recent reports describing the peripheral and central effects of adiponectin and discuss progress concerning its molecular mechanisms. We will also particularly focus on apparent controversies and related mechanisms associated with the central effects of adiponectin on energy homeostasis.
The Journal of nutritional biochemistry 09/2009; 20(11):831-9. · 4.29 Impact Factor
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ABSTRACT: Uranium is a heavy metal naturally present in the environment that may be chronically ingested by the population. Previous studies have shown that uranium is present in the brain and alters behaviour, notably locomotor activity, sensorimotor ability, sleep/wake cycle and the memory process, but also metabolism of neurotransmitters. The cholinergic system mediates many cognitive systems, including those disturbed after chronic exposure to uranium i.e., spatial memory, sleep/wake cycle and locomotor activity. The objective of this study was to assess whether these disorders follow uranium-induced alteration of the cholinergic system. In comparison with 40 control rats, 40 rats drank 40 mg/L uranyl nitrate for 1.5 or 9 months. Cortex and hippocampus were removed and gene expression and protein level were analysed to determine potential changes in cholinergic receptors and acetylcholine levels. The expression of genes showed various alterations in the two brain areas after short- and long-term exposure. Nevertheless, protein levels of the choline acetyltransferase enzyme (ChAT), the vesicular transporter of acetylcholine (VAChT) and the nicotinic receptor beta2 sub-unit (nAChRbeta2) were unmodified in all cases of the experiment and muscarinic receptor type 1 (m1AChR) protein level was disturbed only after 9 months of exposure in the cortex (-30%). Acetylcholine levels were unchanged in the hippocampus after 1.5 and 9 months, but were decreased in the cortex after 1.5 months only (-22%). Acetylcholinesterase (AChE) activity was also unchanged in the hippocampus but decreased in the cortex after 1.5 and 9 months (-16% and -18%, respectively). Taken together, these data indicate that the cholinergic system is a target of uranium exposure in a structure-dependent and time-dependent manner. These cholinergic alterations could participate in behavioural impairments.
Toxicology 06/2009; 261(1-2):59-67. · 3.68 Impact Factor
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ABSTRACT: Growing evidences suggest that obesity is associated with hypothalamic leptin resistance, leading to the alteration of food intake control. Alternative treatment using ciliary neurotrophic factor (CNTF) has been suggested because CNTF exerts a leptin-like effect, even in leptin-resistant states, but the mechanisms by which CNTF maintains this effect are not yet understood. Both leptin and CNTF act in the hypothalamus through similar signaling pathways including janus kinase-2/signal transducer and activator of transcription (STAT)-3 pathway. To explore the differences and interactions between leptin and CNTF signaling pathways, differentiated human neuroblastoma cells (SH-SY5Y) were exposed to either leptin or CNTF and then challenged for each cytokine. Leptin pretreatment completely abolished leptin-dependent STAT-3 and ERK 1/2 phosphorylations without affecting CNTF action. The lack of cross-desensitization between leptin and CNTF signaling pathways occurred despite the induction of suppressor of cytokine signaling-3 in response to both cytokines. Interestingly, leptin as well as insulin induced the expression of phosphotyrosine phosphatase (PTP)-1B, whereas CNTF treatment did not affect its expression. In addition, acute leptin treatment but not CNTF induced PTP-1B expression in mouse hypothalamic arcuate nucleus. Furthermore, the overexpression of human PTP-1B in SH-SY5Y cells completely abolished leptin- and insulin-dependent janus kinase-2, STAT-3, and ERK 1/2 phosphorylations, but CNTF action was not altered. Collectively, our results suggest that PTP-1B constitutes a key divergent element between leptin/insulin and CNTF signaling pathways at the neuronal level, which may constitute a possible mechanism that explains the efficacy of CNTF in leptin-resistant states.
Endocrinology 12/2008; 150(3):1182-91. · 4.46 Impact Factor
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ABSTRACT: Adiponectin is involved in the control of energy homeostasis in peripheral tissues through Adipor1 and Adipor2 receptors. An increasing amount of evidence suggests that this adipocyte-secreted hormone may also act at the hypothalamic level to control energy homeostasis. In the present study, we observed the gene and protein expressions of Adipor1 and Adipor2 in rat hypothalamus using different approaches. By immunohistochemistry, Adipor1 expression was ubiquitous in the rat brain. By contrast, Adipor2 expression was more limited to specific brain areas such as hypothalamus, cortex, and hippocampus. In arcuate and paraventricular hypothalamic nuclei, Adipor1, and Adipor2 were expressed by neurons and astrocytes. Furthermore, using transgenic green fluorescent protein mice, we showed that Adipor1 and Adipor2 were present in pro-opiomelanocortin (POMC) and neuropeptide Y (NPY) neurons in the arcuate nucleus. Finally, adiponectin treatment by intracerebroventricular injection induced AMP-activated protein kinase (AMPK) phosphorylation in the rat hypothalamus. This was confirmed by in vitro studies using hypothalamic membrane fractions. In conclusion, Adipor1 and Adipor2 are both expressed by neurons (including POMC and NPY neurons) and astrocytes in the rat hypothalamic nuclei. Adiponectin is able to increase AMPK phosphorylation in the rat hypothalamus. These data reinforced a potential role of adiponectin and its hypothalamic receptors in the control of energy homeostasis.
Journal of Endocrinology 11/2008; 200(1):93-105. · 3.55 Impact Factor
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ABSTRACT: Emerging evidence showed that variations in environmental temperature affect both leptin and uncoupling protein (UCP) gene expression in mammals, whereas a little is known about such interactions in birds. Thus, we conducted the present study to investigate the influence of acute (2 hours) cold (4 degrees C) and chronic (10 days) heat (32 degrees C) exposure on hepatic leptin and muscle UCP gene expression in 5-wk-old broiler chickens. Both cold- and heat-exposure significantly (P < 0.05 to P < 0.001) upregulated hepatic leptin (by 35 and 46%, respectively) and muscle UCP mRNA levels (by 71 and 71%, respectively) compared to the thermoneutrality (22 degrees C). This result suggests that leptin and UCP may be involved in the thermoregulation response of chickens to extreme climate (cold and hot temperatures). The upregulation of hepatic leptin gene expression was accompanied by an increase in plasma leptin levels, indicating that leptin may be regulated at transcriptional level. The increase of leptin and UCP mRNA abundance, and leptinemia we report here were not related to plasma glucose or insulin levels. In conclusion, the exposure of broiler chickens to extreme ambient temperatures (cold and heat) increases hepatic leptin and muscle UCP gene expression.
Journal of Experimental Zoology Part A Ecological Genetics and Physiology 09/2008; 309(7):381-8. · 1.64 Impact Factor
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Jacqueline Férézou-Viala,
Anne-France Roy,
Colette Sérougne,
Daniel Gripois,
Michel Parquet,
Virginie Bailleux,
Arieh Gertler,
Bernadette Delplanque,
Jean Djiane,
Michel Riottot, Mohammed Taouis
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ABSTRACT: Epidemiological and animal studies suggest that the alteration of hormonal and metabolic environment during fetal and neonatal development can contribute to development of metabolic syndrome in adulthood. In this paper, we investigated the impact of maternal high-fat (HF) diet on hypothalamic leptin sensitivity and body weight gain of offspring. Adult Wistar female rats received a HF or a control normal-fat (C) diet for 6 wk before gestation until the end of the suckling period. After weaning, pups received either C or HF diet during 6 wk. Body weight gain and metabolic and endocrine parameters were measured in the eight groups of rats formed according to a postweaning diet, maternal diet, and gender. To evaluate hypothalamic leptin sensitivity in each group, STAT-3 phosphorylation was measured in response to leptin or saline intraperitoneal bolus. Pups exhibited similar body weights at birth, but at weaning, those born to HF dams weighed significantly less (-12%) than those born to C dams. When given the HF diet, males and females born to HF dams exhibited smaller body weight and feed efficiency than those born to C dams, suggesting increased energy expenditure programmed by the maternal HF diet. Thus, maternal HF feeding could be protective against adverse effects of the HF diet as observed in male offspring of control dams: overweight (+17%) with hyperleptinemia and hyperinsulinemia. Furthermore, offspring of HF dams fed either C or HF diet exhibited an alteration in hypothalamic leptin-dependent STAT-3 phosphorylation. We conclude that maternal high-fat diet programs a hypothalamic leptin resistance in offspring, which, however, fails to increase the body weight gain until adulthood.
AJP Regulatory Integrative and Comparative Physiology 10/2007; 293(3):R1056-62. · 3.34 Impact Factor
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ABSTRACT: Emerging evidence suggests a potential role of stearoyl-CoA desaturase (SCD)-1 in the control of body weight and energy homeostasis. The present study was conducted to investigate the effects of several energy balance-related factors (leptin, cerulenin, food deprivation, genotype, and gender) on SCD gene expression in chickens. In experiment 1, 6-week-old female and male broiler chickens were used. In experiment 2, two groups of 3-week-old broiler chickens were continuously infused with recombinant chicken leptin (8 micro g/kg/h) or vehicle for 6 h. In experiment 3, two groups of 2-week-old broiler chickens received i.v. injections of cerulenin (15 mg/kg) or vehicle. In experiment 4, two broiler chicken lines (fat and lean) were submitted to two nutritional states (food deprivation for 16 or 24 h and feeding ad libitum). At the end of each experiment, tissues were collected for analyzing SCD gene expression. Data from experiment 1 showed that SCD is ubiquitously expressed in chicken tissues with highest levels in the proventriculus followed by the ovary, hypothalamus, kidney, liver, and adipose tissue in female, and hypothalamus, leg muscle, pancreas, liver, and adipose tissue in male. Female chickens exhibited significantly higher SCD mRNA levels in kidney, breast muscle, proventriculus, and intestine than male chickens. However, hypothalamic SCD gene expression was higher in male than in female (P < 0.05). Leptin increased SCD gene expression in chicken liver (P < 0.05), whereas cerulenin decreased SCD mRNA levels in muscle. Both leptin and cerulenin significantly reduced food intake (P < 0.05). Food deprivation for either 16 or 24 h decreased the hepatic SCD gene expression in fat line and lean line chickens compared with their fed counterparts (P < 0.05). The hypothalamic SCD mRNA levels were decreased in both lines only after 24 h of food deprivation (P < 0.05). In conclusion, SCD is ubiquitously expressed in chickens and it is regulated by leptin, cerulenin, nutritional state, and gender in a tissue-specific manner.
Journal of Endocrinology 02/2007; 192(1):229-36. · 3.55 Impact Factor
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ABSTRACT: The insulin-sensitive glucose transporter Glut4 is expressed in brain areas that regulate energy homeostasis and body adiposity. In contrast with peripheral tissues, however, the impact of insulin on Glut4 plasma membrane (PM) translocation in neurons is not known. In this study, we examined the role of two anorexic hormones (leptin and insulin) on Glut4 translocation in a human neuronal cell line that express endogenous insulin and leptin receptors. We show that insulin and leptin both induce Glut4 translocation to the PM of neuronal cells and activate glucose uptake. Wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase, totally abolished insulin- and leptin-dependent Glut4 translocation and stimulation of glucose uptake. Thus, Glut4 translocation is a phosphatidylinositol 3-kinase-dependent mechanism in neuronal cells. Next, we investigated the impact of chronic insulin and leptin treatments on Glut4 expression and translocation. Chronic exposure of neuronal cells to insulin or leptin down-regulates Glut4 proteins and mRNA levels and abolishes the acute stimulation of glucose uptake in response to acute insulin or leptin. In addition, chronic treatment with either insulin or leptin impaired Glut4 translocation. A cross-desensitization between insulin and leptin was apparent, where exposure to insulin affects leptin-dependent Glut4 translocation and vice versa. This cross-desensitization could be attributed to the increase in suppressor of cytokine signaling-3 expression, which was demonstrated in response to each hormone. These results provide evidence to suggest that Glut4 translocation to neuronal PM is regulated by both insulin and leptin signaling pathways. These pathways might contribute to an in vivo glucoregulatory reflex involving a neuronal network and to the anorectic effect of insulin and leptin.
Endocrinology 06/2006; 147(5):2550-6. · 4.46 Impact Factor
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ABSTRACT: The present work aimed to study in rats whether substitution of a low level of fish oil (FO; 2.2% of calories) into a low-fat diet (6.6% of calories from fat as peanut-rape oil or control diet) 1) has a tissue-specific effect on insulin signaling pathway and 2) prevents dexamethasone-induced alteration of insulin signaling in liver, muscle, and adipose tissue. Sixteen rats were used for study of insulin signaling, and sixteen rats received an oral glucose load (3 g/kg). Eight rats/group consumed control diet or diet containing FO over 5 wk. Four rats from each group received a daily intraperitoneal injection of saline or dexamethasone (1 mg.kg(-1).day(-1)) for the last 5 days of feeding. In liver, FO decreased phosphatidylinositol 3'-kinase (PI 3'-kinase) activity by 54% compared with control diet. A similar result was obtained in muscle. In both liver and muscle, FO clearly amplified the effect of dexamethasone. FO did not alter early steps of insulin signaling, and in muscle GLUT4 protein content remained unaltered. In adipose tissue, FO increased PI 3'-kinase activity by 74%, whereas dexamethasone decreased it by 65%; inhibition of PI 3'-kinase activity by dexamethasone was similar in rats fed FO or control diet, and GLUT4 protein content was increased by 61% by FO. Glycemic and insulinemic responses to oral glucose were not modified by FO. In conclusion, FO increased PI 3'-kinase activity in adipose tissue while inhibiting it in liver and muscle. The maintenance of whole body glucose homeostasis suggests an important role of adipose tissue for control of glucose homeostasis.
AJP Endocrinology and Metabolism 02/2006; 290(1):E78-E86. · 4.75 Impact Factor
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ABSTRACT: Leptin is reported to have direct effects on lipogenesis in peripheral tissues that are independent of its central effects on food intake and body weight. These experiments have been mainly carried out in rodents (different models of obesity) in which lipogenesis occurs in both adipose tissue and liver. Such effects are unknown in birds in which lipogenesis occurs essentially in the liver. In this study, leptin gene expression and circulating leptin levels were examined in two chicken lines, selected for high (FL) or low (LL) abdominal fat pad size, at different nutritional states (fasted and fed state). In addition, effects of recombinant chicken leptin on liver metabolism were investigated. Hepatic leptin and fatty acid synthase (FAS) gene expression and plasma leptin levels were significantly higher in FL than in LL chickens (P < 0.05). In both lines, fasting significantly reduced hepatic leptin and FAS mRNA levels (P < 0.05). Continuous administration of recombinant chicken leptin (8 microg/kg/h) during 6 h significantly inhibited food intake (51%) and increased leptinemia (23-fold) compared to untreated group. Despite the decrease of food intake, leptin significantly induced the expression of FAS in chicken liver. These changes were accompanied by a significant down-regulation of leptin receptor gene expression, however SREBP-1, the main transcription factor of lipogenic genes, remained unchanged. This result suggests a local potential role of leptin in the regulation of avian hepatic lipogenesis, and explain, at least partly, the metabolic changes evolved during the divergent selection of FL and LL chickens.
Domestic Animal Endocrinology 12/2005; 29(4):646-60. · 2.06 Impact Factor
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ABSTRACT: Leptin resistance contributes to the pathogenesis of common obesity related metabolic diseases, including insulin resistance. However, the relationship between leptin and insulin resistance is not clearly established. Here, we show that induced hyperleptinemia by leptin infusion alters insulin signalling in rat liver. Leptin infusion clearly reduced the insulin or leptin dependent IRS-1/IRS-2 association to p85 regulatory subunit of PI 3-kinase. Leptin infusion also abolished STAT-3 phosphorylation in response to insulin or leptin and similar results were obtained for MAP-kinase phosphorylation. Hypothalamic leptin resistance was also induced by leptin infusion since leptin was unable to induce STAT-3 phosphorylation. These results provide evidence that induced hyperleptinemia can contribute to the onset of insulin resistance at least at the hepatic level.
Molecular and Cellular Endocrinology 11/2005; 242(1-2):59-66. · 4.19 Impact Factor
