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Lipid biosynthesis enzyme Agpat5 in AgRP-neurons is required for insulin-induced hypoglycemia sensing and glucagon secretion
During hypoglycemia, glucagon secretion is part of the mechanism needed to restore normal blood glucose levels. Here, Strembitska et al. report that sensing of hypoglycemia by AgRP neurons requires Agpat5, an enzyme which prevents fatty acids from entering the mitochondria for ATP production, ensuring correct neuronal activation and glucagon secretion.
- Anastasiya Strembitska
- , Gwenaël Labouèbe
- & Bernard Thorens
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Article
| Open Access
MicroRNA-7 regulates melanocortin circuits involved in mammalian energy homeostasis
The hypothalamus controls systemic energy homeostasis. Here, the authors show that loss of microRNA-7 in hypothalamic neurons causes obesity, increased growth and endocrine dysfunction in mice, and report genetic evidence that links microRNA-7 to height and adiposity in humans.
- Mary P. LaPierre
- , Katherine Lawler
- & Markus Stoffel
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| Open Access
Brain adiponectin signaling controls peripheral insulin response in Drosophila
Circulating adiponectin controls sensitivity to insulin in tissues. Here, Arquier et al. show that adiponectin receptor activity in neurons of the Drosophila brain controls insulin response in peripheral tissues via juvenile hormone signaling.
- Nathalie Arquier
- , Marianne Bjordal
- & Pierre Léopold
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| Open Access
Prostaglandin in the ventromedial hypothalamus regulates peripheral glucose metabolism
The ventromedial hypothalamus regulates systemic glucose metabolism. Here the authors show that cytosolic phospholipase A2 mediated phospholipid metabolism contributes to this regulation in healthy animals but exert deteriorating effects on glucose homeostasis under high-fat-diet feeding.
- Ming-Liang Lee
- , Hirokazu Matsunaga
- & Chitoku Toda
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| Open Access
The endoplasmic reticulum stress-autophagy pathway controls hypothalamic development and energy balance regulation in leptin-deficient neonates
Overnutrition is associated with hypothalamic ER stress and impaired leptin signaling. Here the authors show that ER stress already occurs in neonates and that treatment with the ER stress relieving drug TUDCA early in life has beneficial metabolic and neurodevelopmental effects.
- Soyoung Park
- , Aleek Aintablian
- & Sebastien G. Bouret
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Article
| Open Access
Glycogen branching enzyme controls cellular iron homeostasis via Iron Regulatory Protein 1 and mitoNEET
Higher organisms regulate cellular iron concentrations through Iron Regulatory Proteins (IRPs), which regulate specific messenger RNAs. Here Huynh et al. show that IRP1 requires a Glycogen Branching Enzyme for proper function, and that IRP1 has additional regulatory roles in cell nuclei.
- Nhan Huynh
- , Qiuxiang Ou
- & Kirst King-Jones
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Article
| Open Access
Central nicotine induces browning through hypothalamic κ opioid receptor
Nicotine reduces food intake and increases energy expenditure in brown adipose tissue. Here the authors show that nicotine also induces white adipose tissue browning via central kappa opioid receptor action.
- Patricia Seoane-Collazo
- , Laura Liñares-Pose
- & Miguel López
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Article
| Open Access
Regulation of substrate utilization and adiposity by Agrp neurons
Agouti-related peptide (AgRP) producing neurons regulate food intake and metabolic processes in peripheral organs. Here, the authors show that hypothalamic AgRP neurons alter whole body substrate utilization to favour carbohydrate usage and lipid storage.
- João Paulo Cavalcanti-de-Albuquerque
- , Jeremy Bober
- & Marcelo O. Dietrich
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| Open Access
TAp63 contributes to sexual dimorphism in POMC neuron functions and energy homeostasis
Sexual dimorphism exists in a number of physiological processes, including energy homeostasis. Here, the authors show that pro-opiomelanocortin neurons in female mice fire more rapidly than males, and that deletion of the transcription TAp63 leads to a reduced neuronal firing rate and a male-like susceptibility to diet-induced obesity.
- Chunmei Wang
- , Yanlin He
- & Yong Xu
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Article
| Open Access
Sex differences in microglial CX3CR1 signalling determine obesity susceptibility in mice
Unlike males, female mice are resistant to hypothalamic inflammation and weight gain when fed a high-fat diet. Here, the authors reveal sex-specific regulation of hypothalamic microglial activation through CX3CR1 signalling, providing a potential mechanism for differential susceptibility to diet-induced obesity.
- Mauricio D. Dorfman
- , Jordan E. Krull
- & Joshua P. Thaler
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| Open Access
A tachykinin-like neuroendocrine signalling axis couples central serotonin action and nutrient sensing with peripheral lipid metabolism
Serotonin is a potent stimulator of fat loss and energy expenditure in several species, includingC. elegans. Here, Palamiuc et al. identify the neuropeptide, FP-7, and its receptor in the intestine, NRP-22 as mediators of serotonergic body fat loss in worms.
- Lavinia Palamiuc
- , Tallie Noble
- & Supriya Srinivasan
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Article
| Open Access
Inhibition of glycine transporter-1 in the dorsal vagal complex improves metabolic homeostasis in diabetes and obesity
Glycine sensing in the dorsal vagal complex (DVC) regulates hepatic glucose production in rodents. Here the authors show that pharmacological and molecular inhibition of glycine reuptake in the DVC potentiates NMDA receptors, and improves metabolic homeostasis in animal models of obesity and diabetes.
- Jessica T. Y. Yue
- , Mona A. Abraham
- & Tony K. T. Lam
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Article
| Open Access
ZBTB20 is required for anterior pituitary development and lactotrope specification
The pituitary is a complex structure with the anterior lobe containing five specialized cell types secreting different hormones. Here Cao et al. unravel a role for ZBTB20 in pituitary development and specifically in lactrotrope specification.
- Dongmei Cao
- , Xianhua Ma
- & Weiping J. Zhang
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| Open Access
Functional anterior pituitary generated in self-organizing culture of human embryonic stem cells
It is difficult to generate functional human anterior pituitary tissues in vitro. Here, Ozone et al. generate human anterior pituitary from embryonic stem cells by recapitulating in vivodevelopment, and demonstrate this tissue secretes hormones and rescues hypopituitarism when grafted into mice.
- Chikafumi Ozone
- , Hidetaka Suga
- & Yoshiki Sasai
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| Open Access
Sex-specific regulation of follicle-stimulating hormone secretion by synaptotagmin 9
Pituitary gonadotropes secrete follicle-stimulating hormone (FSH) in both male and female mice. Roper et al.show that the synaptotagmin isoform syt-9 is specifically required for FSH secretion, but only in females, revealing a mechanism by which specificity can be encoded in complex secretory cells.
- Lindsey K. Roper
- , Joseph S. Briguglio
- & Edwin R. Chapman
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| Open Access
Antagonistic interplay between hypocretin and leptin in the lateral hypothalamus regulates stress responses
The hypothalamic-pituitary-adrenal axis coordinates behavioral and physiological responses to stress but the mechanisms are poorly understood. Here, the authors show that neurons that produce hypocretin/orexin in the lateral hypothalamic area regulate corticosterone release and a variety of behaviors related to the stress response.
- Patricia Bonnavion
- , Alexander C. Jackson
- & Luis de Lecea
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| Open Access
Serotonergic neurons respond to nutrients and regulate the timing of steroid hormone biosynthesis in Drosophila
Steroidal hormones play a major role in the transition from juvenile-to-adult stages of development. Here, Shimada-Niwa and Niwa show that production of one such hormone in the prothoracic gland of Drosophila melanogaster, is regulated by a subset of serotonergic neurons innervating the prothoracic gland.
- Yuko Shimada-Niwa
- & Ryusuke Niwa
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Article
| Open Access
H2S and NO cooperatively regulate vascular tone by activating a neuroendocrine HNO–TRPA1–CGRP signalling pathway
Nitric oxide (NO) and hydrogen sulphide (H2S) are two gaseous signalling molecules produced in tissues. Here the authors propose that NO and H2S react with each other to form nitroxyl (HNO), which activates the TRPA1 channel in nerve cells and triggers the release of the vasoactive peptide CGRP.
- Mirjam Eberhardt
- , Maria Dux
- & Milos R. Filipovic
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Ablation of TrkB signalling in CCK neurons results in hypercortisolism and obesity
Glucocorticoid levels in the body are controlled by an intricate feedback system acting on the hypothalamus. Here the authors provide molecular insight into this process, identifying TrkB signalling in cholecystokinin-GABAergic neurons as a key component of hypothalamic glucocorticoid signalling.
- Mirjam Geibel
- , Sylvia Badurek
- & Liliana Minichiello
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Neonatal testosterone suppresses a neuroendocrine pulse generator required for reproduction
The milk-ejection reflex in mammals requires the coordinated bursting of oxytocin neurons in the hypothalamus. Here, Israel et al.show that the rhythmic bursting behaviour displayed by these neurons is active in both male and female neonatal rats, but is inactivated in males after the first week of life.
- Jean-Marc Israel
- , Jean-Marie Cabelguen
- & Philippe Ciofi
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| Open Access
Hypothalamic inhibition of socio-sexual behaviour by increasing neuroestrogen synthesis
The conversion of testosterone into oestrogen in the brain is implicated in male aggressive behaviour. Ubuka et al.show that gonadotropin-inhibitory hormone inhibits male aggression by increasing oestrogen synthesis in the brain beyond its optimum concentration for the expression of aggressive behaviour.
- Takayoshi Ubuka
- , Shogo Haraguchi
- & Kazuyoshi Tsutsui
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Human hypocretin and melanin-concentrating hormone levels are linked to emotion and social interaction
The emotional state of humans depends on the temporal concentration of neurochemicals. Blouin et al. measure temporal changes in two neuropeptides, hypocretin and melanin-concentrating hormone, and find that hypocretin but not melanin-concentrating hormone is linked to positive emotions and social interaction.
- Ashley M. Blouin
- , Itzhak Fried
- & Jerome M. Siegel
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Phosphatidylinositol(4,5)bisphosphate coordinates actin-mediated mobilization and translocation of secretory vesicles to the plasma membrane of chromaffin cells
The role of phosphatidylinositol(4,5)bisphosphate in exocytosis is unclear. This study shows that inhibition of the p110δ isoform of PI3-kinase promotes a transient increase in phosphatidylinositol(4,5)bisphosphate, leading to a potentiation of exocytosis in chromaffin cells.
- Peter J. Wen
- , Shona L. Osborne
- & Frédéric A. Meunier
Intra-pituitary follicle-stimulating hormone signaling regulates hepatic lipid metabolism in mice