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| Open AccessmicroRNA-33 controls hunger signaling in hypothalamic AgRP neurons
AgRP neurons regulate feeding behavior by promoting signals of hunger. Here, the authors show that miR-33, represses the activity of AgRP neurons, and selective loss of miR-33 in AgRP neurons promotes obesity and metabolic dysfunction in mice.
- Nathan L. Price
- , Pablo Fernández-Tussy
- & Carlos Fernández-Hernando
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| Open AccessLateral hypothalamic glutamatergic inputs to VTA glutamatergic neurons mediate prioritization of innate defensive behavior over feeding
VTA glutamatergic neurons mediate innate defensive behaviors. Here, authors show that suppression of feeding induced by escape responses to threats is mediated by VTA glutamatergic neurons regulated by lateral hypothalamic glutamatergic neurons.
- M. Flavia Barbano
- , Shiliang Zhang
- & Marisela Morales
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| Open AccessLateral hypothalamic proenkephalin neurons drive threat-induced overeating associated with a negative emotional state
Stress-induced negative emotion results in comfort eating. Here authors identify the enkephalinergic LH circuit and its interaction with stress hormone, corticosterone, as crucial players in the threat-induced emotional eating for palatable foods.
- In-Jee You
- , Yeeun Bae
- & Sora Shin
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| Open AccessAdrenergic modulation of melanocortin pathway by hunger signals
Melanocortin pathway’s role in appetite regulation is a well-stablished. Here, authors describe a novel mechanism by which melanocortin pathway is regulated by ascending adrenergic input from brainstem during hunger and hypoglycemia.
- Nilufer Sayar-Atasoy
- , Connor Laule
- & Deniz Atasoy
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| Open AccessA sex-specific thermogenic neurocircuit induced by predator smell recruiting cholecystokinin neurons in the dorsomedial hypothalamus
Predator cue detection is associated with changes in feeding and energy expenditure processes. Here the authors show that female mice exhibit heightened stress-dependent metabolic changes and report that this response is integrated by neurons within the dorsomedial hypothalamus.
- Predrag Jovanovic
- , Allan-Hermann Pool
- & Celine E. Riera
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| Open AccessThe melanocortin action is biased toward protection from weight loss in mice
Melanocortin action is known to regulate body weight. Here the authors report that while inhibition of the hypothalamic melanocortin action leads to obesity in mice, chronic activation of melanocortin action is not sufficient to cause weight loss.
- Hongli Li
- , Yuanzhong Xu
- & Qingchun Tong
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| Open AccessHypothalamic melanin-concentrating hormone neurons integrate food-motivated appetitive and consummatory processes in rats
Food intake is determined by learned appetitive responses and physiological “appetition” signals after eating begins. Here, authors show melanin-concentrating hormone (MCH)-producing neurons integrate these processes to promote caloric intake.
- Keshav S. Subramanian
- , Logan Tierno Lauer
- & Scott E. Kanoski
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| Open AccessLateral hypothalamic leptin receptor neurons drive hunger-gated food-seeking and consummatory behaviours in male mice
Eating behviours consist of seeking and consummatory phases. Here, authors show that two distinct lateral hypothalamic leptin receptor neurons orchestrate seeking and consummatory phases of eating behaviour via hunger signal, Neuropeptide Y.
- Young Hee Lee
- , Yu-Been Kim
- & Hyung Jin Choi
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Article
| Open AccessLipid 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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| Open AccessMicroRNA-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 AccessA temperature-regulated circuit for feeding behavior
Feeding behavior is modulated by ambient temperature, as lower temperatures increase the necessity for energy intake and vice versa. Here the authors identify neuronal pathways that control feeding in a temperature-dependent manner.
- Shaowen Qian
- , Sumei Yan
- & Yi Zhou
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Article
| Open AccessNTS Prlh overcomes orexigenic stimuli and ameliorates dietary and genetic forms of obesity
Calcitonin receptor-expressing neurons of the nucleus tractus solitarius contribute to long-term control of food intake and body weight. The authors show that a subset of these cells expresses Prlh and that enhancing Prlh-mediated neurotransmission from the NTS dampens hypothalamically-driven hyperphagia and obesity in mice.
- Wenwen Cheng
- , Ermelinda Ndoka
- & Martin G. Myers Jr
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| Open AccessProstaglandin 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 AccessLipocalin 2 mediates appetite suppression during pancreatic cancer cachexia
Lipocalin 2 (LCN2) has been recently identified as an endogenous regulator of appetite. Here, using pancreatic cancer as a model of cachexia, the authors demonstrate that LCN2 is a critical mediator of cancer-associated anorexia and may be therapeutically targeted to improve patient outcomes.
- Brennan Olson
- , Xinxia Zhu
- & Daniel L. Marks
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| Open AccessTrkB-expressing paraventricular hypothalamic neurons suppress appetite through multiple neurocircuits
The TrkB receptor is known to regulate obesity via appetite control, but the underlying neural circuits are not known. Here, the authors show that selective modulation of TrkB+ neurons in the paraventricular hypothalamus regulates food intake via circuits to ventromedial hypothalamus and lateral parabrachial nucleus.
- Juan Ji An
- , Clint E. Kinney
- & Baoji Xu
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| Open AccessDNA methylation in AgRP neurons regulates voluntary exercise behavior in mice
AgRP neurons in the hypothalamic arcuate nucleus (ARH) are involved in regulating hunger and energy balance. Here the authors show that knockout of the DNA methyltransferase Dnmt3a in AgRP neurons of the ARH leads to a reduction in voluntary exercise along with numerous epigenetic and gene expression changes in ARH neurons.
- Harry MacKay
- , C. Anthony Scott
- & Robert A. Waterland
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| Open AccessHypothalamic neuronal circuits regulating hunger-induced taste modification
Hunger modulates perception of good and bad tastes. Here, the authors report that orexigenic AgRP neurons in the hypothalamus mediate these effects through glutamatergic lateral hypothalamic neurons that send distinct projections to the lateral septum and lateral habenula.
- Ou Fu
- , Yuu Iwai
- & Ken-ichiro Nakajima
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| Open AccessGrowth hormone regulates neuroendocrine responses to weight loss via AgRP neurons
Reduction in food intake elicits neuroendocrine adaptations to counterregulate the negative energy balance, e.g. via reduction in leptin levels. Here, the authors identify an additional starvation signal, growth hormone (GH). Blocking GH receptor attenuates the fall of whole body energy expenditure during food deprivation in mice.
- Isadora C. Furigo
- , Pryscila D. S. Teixeira
- & J. Donato Jr
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| Open AccessRegulation 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 AccessDiet-induced adaptive thermogenesis requires neuropeptide FF receptor-2 signalling
Excess caloric intake leads to increased thermogenesis in brown adipose tissue, to limit weight gain. Here, the authors show that neuropeptide FF receptor-2 signalling promotes thermogenesis via control of NPY expression in the arcuate nucleus, and that it absence in mice leads to a failure of activation of diet-induced thermogenesis and the development of exacerbated obesity.
- Lei Zhang
- , Chi Kin Ip
- & Herbert Herzog
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| Open AccessTAp63 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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| Open AccessA neural basis for antagonistic control of feeding and compulsive behaviors
Feeding disorders are often comorbid with compulsive behaviours but the underlying neural circuits are not known. Here the authors demonstrate that glutamatergic and GABAergic projections from the LH to the PVH exert antagonistic effects on grooming and feeding via modulation of PVH neuron activity.
- Leandra R. Mangieri
- , Yungang Lu
- & Qingchun Tong
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| Open AccessMRAP2 regulates ghrelin receptor signaling and hunger sensing
Melanocortin receptor accessory protein 2 (MRAP2) is an adaptor protein that contributes to melanocortin-4 receptor and prokineticin receptor 1 signalling. Here the authors show that MRAP2 also regulates ghrelin receptor signalling in the hypothalamus and starvation sensing in mice.
- Dollada Srisai
- , Terry C. Yin
- & Julien A. Sebag
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| Open AccessMANF regulates hypothalamic control of food intake and body weight
MANF is a neurotrophic factor that is secreted but also mediates the unfolded protein response acting intracellularly. Here, the authors show that MANF expression in the brain is influenced by nutritional cues, and hypothalamic MANF influences food intake and systemic energy homeostasis.
- Su Yang
- , Huiming Yang
- & Xiao-Jiang Li
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Article
| Open AccessCaffeine inhibits hypothalamic A1R to excite oxytocin neuron and ameliorate dietary obesity in mice
The mechanism by which caffeine, an antagonist of adenosine receptors, regulates metabolism is not clear. Here the authors show that adenosine A1R receptor expression is increased in the hypothalamus of diet-induced obesity mice, and that body weight can be alleviated by central administration of caffeine via its action on hypothalamic oxytocin neurons.
- Liufeng Wu
- , Jia Meng
- & Guo Zhang
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Article
| Open AccessSex 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 AccessAgrp neuron activity is required for alcohol-induced overeating
It is well known that alcohol consumption leads to overeating however the neural mechanisms are unclear. Here the authors demonstrate that hunger promoting Agrp neurons in hypothalamus are also activated by ethanol and are necessary for ethanol-induced overeating.
- Sarah Cains
- , Craig Blomeley
- & Denis Burdakov
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Article
| Open AccessInhibition 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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| Open AccessHypothalamic leptin action is mediated by histone deacetylase 5
Histone deacetylases (HDACs) regulate energy metabolism in peripheral tissues, but whether HDACs expressed in the brain influence systemic metabolism is unknown. Here the authors show that hypothalamic HDAC5 expression is affected by the diet and HDAC5 regulates leptin sensitivity by deacetylating STAT3.
- Dhiraj G. Kabra
- , Katrin Pfuhlmann
- & Paul T. Pfluger
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| Open AccessHypothalamic PKA regulates leptin sensitivity and adiposity
Mice lacking RIIβ, a regulatory subunit of protein kinase A, are lean and resistant to diet-induced obesity. Here, the authors show that RIIβ regulates leptin sensitivity, acting as a physiological brake on leptin responsiveness and the duration of leptin signalling in the hypothalamus.
- Linghai Yang
- & G. Stanley McKnight
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| Open AccessSemaphorin7A regulates neuroglial plasticity in the adult hypothalamic median eminence
Reproduction in mammals is dependent on the function of specific neurons that secrete gonadotropin-releasing hormone (GnRH) and project their axons to the median eminence (ME) of the hypothalamus. Here the authors show that Semaphorin7A signaling plays a role in mediating the plasticity of GnRH axon terminals and tanycytes in the ME.
- Jyoti Parkash
- , Andrea Messina
- & Paolo Giacobini
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| Open AccessAntagonistic 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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Clusterin and LRP2 are critical components of the hypothalamic feeding regulatory pathway
Clusterin is widely distributed in tissues and body fluids, and is implicated in various physiological processes. In this study the authors investigate the role of hypothalamic clusterin, and find that clusterin regulates energy metabolism and body weight through the lipoprotein receptor LRP2.
- So Young Gil
- , Byung-Soo Youn
- & Min-Seon Kim
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Haematopoietic cells produce BDNF and regulate appetite upon migration to the hypothalamus
Brain-derived neurotrophic factor is produced in the brain and is a known regulator of energy homoeostasis. Here Urabe and colleagues show that brain-derived neurotrophic factor-producing haematopoietic cells control appetite by migrating into the hypothalamus, where they make contact with neurons.
- Hiroshi Urabe
- , Hideto Kojima
- & Hiroshi Kimura