Hypothalamus

  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article |

    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
  • Article |

    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