Leptin regulated calcium channels of neuropeptide Y and proopiomelanocortin neurons by activation of different signal pathways

Wang, J.-H.; Wang, Fan; Yang, Mei; Yu, Dongfang; Wu, Wenyao; Liu, J.; Ma, Liqun; Cai, Fei; Chen, J.-G.

doi:10.1016/j.neuroscience.2008.04.079

Cited by 59 publications

(57 citation statements)

References 42 publications

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“…In the ARC, proopiomelanocortin (POMC) neurons are excited by leptin (6) via a phosphoinositide 3 kinase-dependent (13,39), AMP kinase-independent (5) mechanism. Although we did not phenotype the ARC neurons tested here, the fact that DIO ARC LepE neurons were less sensitive to leptin suggests that these rats would have a reduced activation of their catabolic POMC neurons as one cause of their propensity to become obese on high-fat diets.…”

Section: Discussionmentioning

confidence: 99%

Ventromedial nucleus neurons are less sensitive to leptin excitation in rats bred to develop diet-induced obesity

Irani¹,

Foll²,

Dunn-Meynell³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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Irani BG, Le Foll C, Dunn-Meynell AA, Levin, BE. Ventromedial nucleus neurons are less sensitive to leptin excitation in rats bred to develop diet-induced obesity. Am J Physiol Regul Integr Comp Physiol 296: R521-R527, 2009. First published December 31, 2008 doi:10.1152/ajpregu.90842.2008.-Maternal obesity accentuates offspring obesity in dams bred to develop diet-induced obesity (DIO) on a 31% fat, high energy (HE) diet but has no effect on offspring of diet-resistant (DR) dams. Only DIO dams became obese on HE diet when they and DR dams were fed 5% fat chow or HE diets throughout gestation and lactation. Leptin sensitivity of dissociated arcuate (ARC) and ventromedial (VMN) hypothalamic nucleus neurons from the 3-to 4-wk-old offspring was assessed using fura-2 calcium imaging to monitor leptin-induced changes in intracellular calcium ([Ca 2ϩ ]i) as an index of neuronal activity. At 0.1, 1, 10 fmol/l leptin, ϳ4 times more VMN and ARC neurons were excited than inhibited by leptin. In the VMN, leptin excited up to 41% fewer neurons, and these excited neurons were less sensitive to increasing doses of leptin in DIO compared with DR offspring. Also, maternal HE diet intake decreased the percentage of leptin-excited VMN neurons in both DIO and DR offspring and decreased the percentage of leptin-inhibited VMN neurons by 36% only in DIO offspring. In the ARC, there were no genotype or maternal diet effects on the percentage of ARC neurons excited by leptin. However, those DR neurons that were leptin excited were more sensitive to leptin than were those from DIO offspring. These data suggest that reduced responsiveness of DIO VMN neurons to leptin's excitatory effects may be an important contributing factor to the reduced anorectic and thermogenic leptin responsiveness of DIO rats in vivo. body weight; neuropeptide Y; Agouti-related peptide; development EPIDEMIOLOGICAL STUDIES IN human beings suggest that maternal obesity is associated with a higher risk of obesity in offspring (2,3,33). Because such studies rarely provide clues regarding the underlying factors promoting offspring obesity, we have used a rat model in which rats are selectively bred to produce polygenically inherited diet-induced obesity (DIO) or diet-resistance (DR) when fed a high-energy (HE), 31% fat diet (21, 24) to identify factors that promote obesity in offspring of obese mothers. Our prior studies showed that maternal obesity in DIO dams throughout gestation and lactation selectively promotes increased obesity in their adult offspring (27). On the other hand, offspring of DR dams do not become more obese as adults, even when their dams are fed a highly palatable diet to make them obese. Furthermore, the increased obesity in offspring of obese DIO dams is associated with abnormal development of central monoamine pathways involved in regulation of energy homeostasis (18). Therefore, the combination of genetic background, maternal diet, and obesity has differential effects on offspring obesity and the development of neural pathways, which play a...

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Section: Discussionmentioning

confidence: 99%

Ventromedial nucleus neurons are less sensitive to leptin excitation in rats bred to develop diet-induced obesity

Irani¹,

Foll²,

Dunn-Meynell³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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“…All experiments conformed to local and international guidelines for the use of animals, and all experimental protocols were approved by the Review Committee for the Use of Human or Animal Subjects of Huazhong University of Science and Technology. Primary cultures of ARC neurons were prepared as previously described (Muroya et al, 2004;Wang et al, 2008) with some modifications. Brain slices containing the entire ARC were prepared from the brains of neonatal Spague-Dawley rats (days 2-3), and the entire ARC was excised from the left and right sides.…”

Section: Methodsmentioning

confidence: 99%

“…Single ARC neurons were immunocytochemically identified as previously reported, with slight modifications (Muroya et al, 2004;Wang et al, 2008). In the voltage-clamp experiments, the cells with typical characteristics of NPY-positive neurons were selected to record, photograph to mark position, and sequence.…”

Section: Methodsmentioning

confidence: 99%

Orexin-A Activates Hypothalamic AMP-Activated Protein Kinase Signaling through a Ca²⁺-Dependent Mechanism Involving Voltage-Gated L-Type Calcium Channel

Zhou

et al. 2013

Mol Pharmacol

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Hypothalamic AMP-activated protein kinase (AMPK) and orexins/ hypocretins are both involved in the control of feeding behavior, but little is known about the interaction between these two signaling systems. Here, we demonstrated that orexin-A elicited significant activation of AMPK in the arcuate nucleus (ARC) of the hypothalamus by elevating cytosolic free Ca 21 involving extracellular calcium influx. Electrophysiological results revealed that orexin-A increased the L-type calcium current via the orexin receptor-phospholipase C-protein kinase C signaling pathway in ARC neurons that produce neuropeptide Y, an important downstream effector of orexin-A's orexigenic effect. Furthermore, the L-type calcium channel inhibitor nifedipine attenuated orexin-A-induced AMPK activation in vitro and in vivo. We found that inhibition of AMPK by either compound C (6-[4-[2-(1-piperidinyl)ethoxy]phenyl]-3-(4-pyridinyl)-pyrazolo[1,5-a]pyrimidine) or the ATPmimetic 9-b-D-arabinofuranoside prevented the appetite-stimulating effect of orexin-A. This action can be mimicked by nifedipine, the blocker of the L-type calcium channel. Our results indicated that orexin-A activates hypothalamic AMPK signaling through a Ca 21 -dependent mechanism involving the voltage-gated L-type calcium channel, which may serve as a potential target for regulating feeding behavior.

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“…Entre las neuronas que expresan receptores de leptina hay neuronas que coexpresan NPy y AgRP, y son inhibidas por la leptina, mientras que otras neuronas que coexpresan POMC y CART son estimuladas por la leptina (Duan et al, 2007;Morton et al, 2006;Wang et al, 2008). En trucha arco iris, al evaluar el efecto del tratamiento con leptina con concentraciones de glucosa (2, 4 y 8 mM) sobre la expresión de neuropéptidos en el hipotálamo y cerebro posterior, se observan dos tipos de respuestas diferentes.…”

Section: Efecto De La Leptina Sobre La Expresión De Factores Orexigénunclassified

Efecto del tratamiento con leptina sobre la actividad del sistema glucosensor y la expresión de neuropéptidos implicados en la regulación de la ingesta de alimento en trucha arcoíris (Onchorhynchus mykiss)

Aguilar

2012

Encuentro

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Efecto del tratamiento con leptina sobre la actividad del sistema glucosensor y la expresión de neuropéptidos implicados en la regulación de la ingesta de alimento en trucha arcoíris (Onchorhynchus mykiss) 78Encuentro No. 93, 78-100, 2012 Efecto del tratamiento con leptina sobre la actividad del sistema glucosensor y la expresión de neuropéptidos implicados en la regulación de la ingesta de alimento en trucha arcoíris (Onchorhynchus mykiss)Ariel J. Aguilar* Recibido: octubre 2012/ Aceptado: noviembre 2012 La presente revisión se focaliza en el efecto modulatorio de la leptina sobre la actividad del sistema glucosensor y la expresión de neuropéptidos orexigénicos y anorexigénicos involucrados en la regulación de la ingesta de alimento en trucha arco iris. De manera similar al efecto que produce en mamíferos, la administración ICV de leptina induce cambios dosis dependiente en los parámetros relacionados con la glucosensibilidad en hipotálamo y cerebro posterior (incrementos del potencial glucolítico y glucogenogénico en coordinación con incrementos de la actividad de glucoquinasa y de los niveles de ARNm de genes involucrados en la respuesta glucosensora) compatible con lo observado en peces bajo condiciones de hiperglucemia, una situación que produce anorexia. La comprensión de la especificidad de la acción de la leptina en peces es menos clara que en mamíferos. Existen evidencias que sugieren que la acción central de la leptina sobre el sistema glucosensor está relacionada con la activación de la vía JAK/STAT e IRS-PI3K. Por otro lado, el tratamiento con leptina ICV incrementa el potencial glucogenolítico en hígado, el cual podría estar asociado con incrementos de la actividad simpática, y en hipotálamo induce decrecimiento de los niveles de ARNm de NPy. Por tanto, considerando la acción orexigénica del NPy en peces, pareciera que el efecto 79Encuentro No. 93, 78-100, 2012 Efecto del tratamiento con leptina sobre la actividad del sistema glucosensor y la expresión de neuropéptidos implicados en la regulación de la ingesta de alimento en trucha arcoíris (Onchorhynchus mykiss) anoréctico de la leptina puede estar mediado por la reducción de la expresión de NPy en el hipotálamo y que esos cambios pueden estar relacionados con la activación del sistema glucosensor.Palabras clave: Sistema glucosensor, leptina, neuropéptidos, ingesta de alimentos, Onchorhynchus mykiss GlucosensibilidadLos peces teleósteos en general son incapaces de disminuir rápidamente los niveles de glucosa circundantes tras una carga de glucosa o tras la ingesta de alimento con altos niveles de carbohidratos, razón por la que se les considera intolerantes a la glucosa (Moon, 2001). El metabolismo de carbohidratos en los peces (especialmente en especies carnívoras) parece jugar un papel secundario al de los lípidos y las proteínas (Hemre et al., 2002). Sin embargo, los carbohidratos son claves para el metabolismo de todas las especies de peces, aunque no está clara su importancia como una vía energética en los tejidos. Entonces, ¿Por qué no ...

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Leptin regulated calcium channels of neuropeptide Y and proopiomelanocortin neurons by activation of different signal pathways

Cited by 59 publications

References 42 publications

Ventromedial nucleus neurons are less sensitive to leptin excitation in rats bred to develop diet-induced obesity

Ventromedial nucleus neurons are less sensitive to leptin excitation in rats bred to develop diet-induced obesity

Orexin-A Activates Hypothalamic AMP-Activated Protein Kinase Signaling through a Ca²⁺-Dependent Mechanism Involving Voltage-Gated L-Type Calcium Channel

Efecto del tratamiento con leptina sobre la actividad del sistema glucosensor y la expresión de neuropéptidos implicados en la regulación de la ingesta de alimento en trucha arcoíris (Onchorhynchus mykiss)

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Leptin regulated calcium channels of neuropeptide Y and proopiomelanocortin neurons by activation of different signal pathways

Cited by 59 publications

References 42 publications

Ventromedial nucleus neurons are less sensitive to leptin excitation in rats bred to develop diet-induced obesity

Ventromedial nucleus neurons are less sensitive to leptin excitation in rats bred to develop diet-induced obesity

Orexin-A Activates Hypothalamic AMP-Activated Protein Kinase Signaling through a Ca2+-Dependent Mechanism Involving Voltage-Gated L-Type Calcium Channel

Efecto del tratamiento con leptina sobre la actividad del sistema glucosensor y la expresión de neuropéptidos implicados en la regulación de la ingesta de alimento en trucha arcoíris (Onchorhynchus mykiss)

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Orexin-A Activates Hypothalamic AMP-Activated Protein Kinase Signaling through a Ca²⁺-Dependent Mechanism Involving Voltage-Gated L-Type Calcium Channel