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hypothalamic regulation of metabolism

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https://www.readbyqxmd.com/read/28229938/participation-of-ghrelin-signalling-in-the-reciprocal-regulation-of-hypothalamic-npy-pomc-mediated-appetite-control-in-amphetamine-treated-rats
#1
Ching-Han Yu, Shu-Chen Chu, Pei-Ni Chen, Yih-Shou Hsieh, Dong-Yih Kuo
Hypothalamic neuropeptide Y (NPY) and proopiomelanocortin (POMC) have been documented to participate in amphetamine (AMPH)-induced appetite suppression. This study investigated whether ghrelin signalling is associated with changes in NPY/POMC-mediated appetite control. Rats were given AMPH daily for four days, and changes in food intake, body weight, plasma ghrelin, hypothalamic NPY, melanocortin 3 receptor (MC3R), ghrelin O-acyltransferase (GOAT), acyl ghrelin (AG) and ghrelin receptor (GHSR1a) were examined and compared...
February 13, 2017: Appetite
https://www.readbyqxmd.com/read/28228474/changes-in-ambient-temperature-elicit-divergent-control-of-metabolic-and-cardiovascular-actions-by-leptin
#2
Jussara M do Carmo, Alexandre A da Silva, Damian G Romero, John E Hall
Interactions of hypothalamic signaling pathways that control body temperature (BT), blood pressure (BP), and energy balance are poorly understood. We investigated whether the chronic BP and metabolic actions of leptin are differentially modulated by changes in ambient temperature (TA ). Mean arterial pressure (MAP), heart rate (HR), BT, motor activity (MA), and oxygen consumption (Vo2) were measured 24 h/d at normal laboratory TA (23°C), at thermoneutral zone (TNZ, 30°C) for mice or during cold exposure (15°C) in male wild-type mice...
February 22, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28219987/a-unique-angiotensin-sensitive-neuronal-population-coordinates-neuroendocrine-cardiovascular-and-behavioral-responses-to-stress
#3
Annette D de Kloet, Lei Wang, Soledad Pitra, Helmut Hiller, Justin A Smith, Yalun Tan, Dani Nguyen, Karlena M Cahill, Colin Sumners, Javier E Stern, Eric G Krause
Stress elicits neuroendocrine, autonomic and behavioral responses that mitigate homeostatic imbalance and ensure survival; however, chronic engagement of such responses promotes psychological, cardiovascular and metabolic impairments. Over recent years, the renin-angiotensin system has emerged as a key mediator of stress responding and its related pathologies, but the neuronal circuits that orchestrate these interactions are not known. These studies combine the use of the Cre-recombinase/loxP system in mice with optogenetics to structurally and functionally characterize angiotensin type-1a receptor-containing neurons of the paraventricular nucleus of the hypothalamus, the goal being to determine the extent of their involvement in the regulation of stress responses...
February 20, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28218622/activation-of-murine-pre-proglucagon-producing-neurons-reduces-food-intake-and-body-weight
#4
Ronald P Gaykema, Brandon A Newmyer, Matteo Ottolini, Vidisha Raje, Daniel M Warthen, Philip S Lambeth, Maria Niccum, Ting Yao, Yiru Huang, Ira G Schulman, Thurl E Harris, Manoj K Patel, Kevin W Williams, Michael M Scott
Peptides derived from pre-proglucagon (GCG peptides) act in both the periphery and the CNS to change food intake, glucose homeostasis, and metabolic rate while playing a role in anxiety behaviors and physiological responses to stress. Although the actions of GCG peptides produced in the gut and pancreas are well described, the role of glutamatergic GGC peptide-secreting hindbrain neurons in regulating metabolic homeostasis has not been investigated. Here, we have shown that chemogenetic stimulation of GCG-producing neurons reduces metabolic rate and food intake in fed and fasted states and suppresses glucose production without an effect on glucose uptake...
February 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28214555/identification-of-a-fatty-acid-binding-protein4-ucp2-axis-regulating-microglial-mediated-neuroinflammation
#5
Cayla M Duffy, Hongliang Xu, Joshua P Nixon, David A Bernlohr, Tammy A Butterick
Hypothalamic inflammation contributes to metabolic dysregulation and the onset of obesity. Dietary saturated fats activate microglia via a nuclear factor-kappa B (NFκB) mediated pathway to release pro-inflammatory cytokines resulting in dysfunction or death of surrounding neurons. Fatty acid binding proteins (FABPs) are lipid chaperones regulating metabolic and inflammatory pathways in response to fatty acids. Loss of FABP4 in peripheral macrophages via either molecular or pharmacologic mechanisms results in reduced obesity-induced inflammation via a UCP2-redox based mechanism...
February 15, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28213613/an-atf4-atg5-signaling-in-hypothalamic-pomc-neurons-regulates-fat-mass-via-affecting-energy-expenditure
#6
Yuzhong Xiao, Yalan Deng, Feixiang Yuan, Tingting Xia, Hao Liu, Zhigang Li, Zhixue Liu, Hao Ying, Yi Liu, Qiwei Zhai, Shanghai Chen, Feifan Guo
Although many biological functions of activating transcription factor 4 (ATF4) have been identified, a role of hypothalamic ATF4 in the regulation of energy homeostasis is poorly understood. Here, we showed that hypothalamic pro-opiomelanocortin (POMC) neurons specific ATF4 knockout (PAKO) mice are lean and have higher energy expenditure. Furthermore, PAKO mice were resistant to high-fat diet (HFD)-induced obesity, glucose intolerance and leptin resistance. Moreover, the expression of autophagy protein 5 (ATG5) was increased or decreased by ATF4 knockdown or over-expression, respectively, and ATF4 inhibited the transcription of ATG5 by binding to the basic zipper-containing protein (bZIP) sites on its promoter...
February 17, 2017: Diabetes
https://www.readbyqxmd.com/read/28199831/inhibition-of-p2y6-signaling-in-agrp-neurons-reduces-food-intake-and-improves-systemic-insulin-sensitivity-in-obesity
#7
Sophie Marie Steculorum, Katharina Timper, Linda Engström Ruud, Nadine Evers, Lars Paeger, Stephan Bremser, Peter Kloppenburg, Jens Claus Brüning
Uridine-diphosphate (UDP) and its receptor P2Y6 have recently been identified as regulators of AgRP neurons. UDP promotes feeding via activation of P2Y6 receptors on AgRP neurons, and hypothalamic UDP concentrations are increased in obesity. However, it remained unresolved whether inhibition of P2Y6 signaling pharmacologically, globally, or restricted to AgRP neurons can improve obesity-associated metabolic dysfunctions. Here, we demonstrate that central injection of UDP acutely promotes feeding in diet-induced obese mice and that acute pharmacological blocking of CNS P2Y6 receptors reduces food intake...
February 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28192062/pomc-neurons-from-birth-to-death
#8
Chitoku Toda, Anna Santoro, Jung Dae Kim, Sabrina Diano
The hypothalamus is an evolutionarily conserved brain structure that regulates an organism's basic functions, such as homeostasis and reproduction. Several hypothalamic nuclei and neuronal circuits have been the focus of many studies seeking to understand their role in regulating these basic functions. Within the hypothalamic neuronal populations, the arcuate melanocortin system plays a major role in controlling homeostatic functions. The arcuate pro-opiomelanocortin (POMC) neurons in particular have been shown to be critical regulators of metabolism and reproduction because of their projections to several brain areas both in and outside of the hypothalamus, such as autonomic regions of the brain stem and spinal cord...
February 10, 2017: Annual Review of Physiology
https://www.readbyqxmd.com/read/28191524/renin-angiotensin-aldosterone-system-in-insulin-resistance-and-metabolic-syndrome
#9
Undurti N Das
Obesity and its consequent complications such as hypertension and metabolic syndrome are increasing in incidence in almost all countries. Insulin resistance is common in obesity. Renin- angiotensin system (RAS) is an important target in the treatment of hypertension and drugs that act on RAS improve insulin resistance and decrease the incidence of type 2 diabetes mellitus, explaining the close association between hypertension and type 2 diabetes mellitus. RAS influences food intake by modulating the hypothalamic expression of neuropeptide Y and orexins via AMPK dephosphorylation...
June 1, 2016: Journal of Translational Internal Medicine
https://www.readbyqxmd.com/read/28190775/drp1-suppresses-leptin-and-glucose-sensing-of-pomc-neurons
#10
Anna Santoro, Michela Campolo, Chen Liu, Hiromi Sesaki, Rosaria Meli, Zhong-Wu Liu, Jung Dae Kim, Sabrina Diano
Hypothalamic pro-opiomelanocortin (POMC) neurons regulate energy and glucose metabolism. Intracellular mechanisms that enable these neurons to respond to changes in metabolic environment are ill defined. Here we show reduced expression of activated dynamin-related protein (pDRP1), a mitochondrial fission regulator, in POMC neurons of fed mice. These POMC neurons displayed increased mitochondrial size and aspect ratio compared to POMC neurons of fasted animals. Inducible deletion of DRP1 of mature POMC neurons (Drp1(fl/fl)-POMC-cre:ER(T2)) resulted in improved leptin sensitivity and glucose responsiveness...
January 30, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28186107/blubber-transcriptome-response-to-acute-stress-axis-activation-involves-transient-changes-in-adipogenesis-and-lipolysis-in-a-fasting-adapted-marine-mammal
#11
J I Khudyakov, C D Champagne, L M Meneghetti, D E Crocker
Stress can compromise an animal's ability to conserve metabolic stores and participate in energy-demanding activities that are critical for fitness. Understanding how wild animals, especially those already experiencing physiological extremes (e.g. fasting), regulate stress responses is critical for evaluating the impacts of anthropogenic disturbance on physiology and fitness, key challenges for conservation. However, studies of stress in wildlife are often limited to baseline endocrine measurements and few have investigated stress effects in fasting-adapted species...
February 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28185867/an-experimental-evaluation-of-the-role-of-the-stress-axis-in-mediating-predator-prey-interactions-in-wild-marine-fish
#12
Michael J Lawrence, Erika J Eliason, Jacob W Brownscombe, Kathleen M Gilmour, John W Mandelman, Steven J Cooke
The hypothalamic-pituitary-interrenal (HPI) axis, through corticosteroid secretion, is an integral mechanism regulating internal homeostasis when vertebrates are faced with a stressor. However, continued HPI-axis stimulation can produce homeostatic overload, where corticosteroids are detrimental to organismal function. This overload condition may play an important role in mediating predator-prey interactions, because chronically/previously stressed animals may have higher rates of predator-induced mortality...
February 7, 2017: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/28179813/sex-differences-in-the-effects-of-androgens-acting-in-the-central-nervous-system-on-metabolism
#13
Jamie Morford, Franck Mauvais-Jarvis
One of the most sexually dimorphic aspects of metabolic regulation is the bidirectional modulation of glucose and energy homeostasis by testosterone in males and females. Testosterone deficiency predisposes men to metabolic dysfunction, with excess adiposity, insulin resistance, and type 2 diabetes, whereas androgen excess predisposes women to insulin resistance, adiposity, and type 2 diabetes. This review discusses how testosterone acts in the central nervous system, and especially the hypothalamus, to promote metabolic homeostasis or dysfunction in a sexually dimorphic manner...
December 2016: Dialogues in Clinical Neuroscience
https://www.readbyqxmd.com/read/28173961/a-screen-for-modulators-reveals-that-orexin-a-rapidly-stimulates-thyrotropin-releasing-hormone-expression-and-release-in-hypothalamic-cell-culture
#14
Antonieta Cote-Vélez, Anabel Martínez Báez, Leticia Lezama, Rosa María Uribe, Patricia Joseph-Bravo, Jean-Louis Charli
In the paraventricular nucleus of the mammalian hypothalamus, hypophysiotropic thyrotropin releasing hormone (TRH) neurons integrate metabolic information and control the activity of the thyroid axis. Additional populations of TRH neurons reside in various hypothalamic areas, with poorly defined connections and functions, albeit there is evidence that some may be related to energy balance. To establish extracellular modulators of TRH hypothalamic neurons activity, we performed a screen of neurotransmitters effects in hypothalamic cultures...
February 2, 2017: Neuropeptides
https://www.readbyqxmd.com/read/28162848/altered-functionality-of-the-corticotrophin-releasing-hormone-receptor-2-in-the-hypothalamic-paraventricular-nucleus-of-hyperphagic-maternally-separated-rats
#15
V Alcántara-Alonso, M I Amaya, G Matamoros-Trejo, P de Gortari
Early-life stress induces endocrine and metabolic alterations that increase food intake and overweight in adulthood. The stress response activates the corticotropin-releasing hormone (CRH) and urocortins' (Ucns) system in the hypothalamic paraventricular nucleus (PVN). These peptides induce anorexic effects through CRH-R2 receptor activation; however, chronic stressed animals develop hyperphagia despite of high PVN CRH expression. We analyzed this paradoxical behavior in adult rats subjected to maternal separation (MS) for 180min/daily during post-natal days 2-14, evaluating their body weight gain, food intake, serum corticosterone and vasopressin concentrations, PVN mRNA expression of CRH-R1, CRH-R2, CRH, Ucn2, Ucn3, vasopressin and CRH-R2 protein levels...
February 1, 2017: Neuropeptides
https://www.readbyqxmd.com/read/28161095/environmental-obesogen-tributyltin-chloride-leads-to-abnormal-hypothalamic-pituitary-gonadal-axis-function-by-disruption-in-kisspeptin-leptin-signaling-in-female-rats
#16
Gabriela C Sena, Leandro C Freitas-Lima, Eduardo Merlo, Priscila L Podratz, Julia F P de Araújo, Poliane A A Brandão, Maria T W D Carneiro, Marina C Zicker, Adaliene V M Ferreira, Christina M Takiya, Carolina M de Lemos Barbosa, Marcelo M Morales, Ana Paula Santos-Silva, Leandro Miranda-Alves, Ian V Silva, Jones B Graceli
Tributyltin chloride (TBT) is a xenobiotic used as a biocide in antifouling paints that has been demonstrated to induce endocrine-disrupting effects, such as obesity and reproductive abnormalities. An integrative metabolic control in the hypothalamus-pituitary-gonadal (HPG) axis was exerted by leptin. However, studies that have investigated the obesogenic TBT effects on the HPG axis are especially rare. We investigated whether metabolic disorders as a result of TBT are correlated with abnormal hypothalamus-pituitary-gonadal (HPG) axis function, as well as kisspeptin (Kiss) action...
March 15, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28144621/glp-1r-signaling-directly-activates-arcuate-nucleus-kisspeptin-action-in-brain-slices-but-does-not-rescue-luteinizing-hormone-inhibition-in-ovariectomized-mice-during-negative-energy-balance
#17
Kristy M Heppner, Arian F Baquero, Camdin M Bennett, Sarah R Lindsley, Melissa A Kirigiti, Baylin Bennett, Martha A Bosch, Aaron J Mercer, Oline K Rønnekleiv, Cadence True, Kevin L Grove, M Susan Smith
Kisspeptin (Kiss1) neurons in the hypothalamic arcuate nucleus (ARC) are key components of the hypothalamic-pituitary-gonadal axis, as they regulate the basal pulsatile release of gonadotropin releasing hormone (GnRH). ARC Kiss1 action is dependent on energy status, and unmasking metabolic factors responsible for modulating ARC Kiss1 neurons is of great importance. One possible factor is glucagon-like peptide 1 (GLP-1), an anorexigenic neuropeptide produced by brainstem preproglucagon neurons. Because GLP fiber projections and the GLP-1 receptor (GLP-1R) are abundant in the ARC, we hypothesized that GLP-1R signaling could modulate ARC Kiss1 action...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28131595/short-day-length-enhances-physiological-resilience-of-the-immune-system-against-2-deoxy-d-glucose-induced-metabolic-stress-in-a-tropical-seasonal-breeder-funambulus-pennanti
#18
Sameer Gupta, Chandana Haldar
Studies demonstrate the importance of metabolic resources in the regulation of reproduction and immune functions in seasonal breeders. In this regard, the restricted energy availability can be considered as an environmental variable that may act as a seasonal stressor and can lead to compromised immune functions. The present study explored the effect of photoperiodic variation in the regulation of immune function under metabolic stress condition. The T-cell-dependent immune response in a tropical seasonal breeder Funambulus pennanti was studied following the inhibition of cellular glucose utilization with 2-deoxy-d-glucose (2-DG)...
January 26, 2017: Hormones and Behavior
https://www.readbyqxmd.com/read/28130409/reduced-metabolism-in-the-hypothalamus-of-the-anorectic-anx-anx-mouse
#19
Ulrika Bergström, Charlotte Lindfors, Marie Svedberg, Jeanette E Johansen, Jenny Häggkvist, Martin Schalling, Rolf Wibom, Abram Katz, Ida Ak Nilsson
The anorectic anx/anx mouse exhibits a mitochondrial complex I dysfunction that is related to aberrant expression of hypothalamic neuropeptides and transmitters regulating food intake. Hypothalamic activity, i.e. neuronal firing and transmitter release, is dependent on glucose utilization and energy metabolism. To better understand the role of hypothalamic activity in anorexia, we assessed carbohydrate and high energy phosphate metabolism, in vivo and in vitro, in the anx/anx hypothalamus. In the fasted state, hypothalamic glucose uptake in the anx/anx mouse was reduced by ~50% of that seen in wild type (wt) mice (P<0...
January 27, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28117213/unraveling-the-role-of-ataxin-2-in-metabolism
#20
REVIEW
Sara Carmo-Silva, Clevio Nobrega, Luís Pereira de Almeida, Claudia Cavadas
Ataxin-2 is a polyglutamine protein implicated in several biological processes such as RNA metabolism and cytoskeleton reorganization. Ataxin-2 is highly expressed in various tissues including the hypothalamus, a brain region that controls food intake and energy balance. Ataxin-2 expression is influenced by nutritional status. Emerging studies discussed here now show that ataxin-2 deficiency correlates with insulin resistance and dyslipidemia, an action mediated via the mTOR pathway, suggesting that ataxin-2 might play key roles in metabolic homeostasis including body weight regulation, insulin sensitivity, and cellular stress responses...
January 20, 2017: Trends in Endocrinology and Metabolism: TEM
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