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Hypothalamic Obesity

P G F Quaresma, L Weissmann, T M Zanotto, A C Santos, A H B de Matos, I C Furigo, F M Simabuco, J D Junior, J C Bittencourt, I Lopes-Cendes, P O Prada
OBJECTIVE: To investigate whether the Cdc2-like Kinase 2 (CLK2) is expressed in hypothalamic neurons and if it is, whether the hypothalamic CLK2 has a role in the regulation of energy balance. SUBJECTS: Swiss mice on chow or high fat diet (HFD) and db/db mice on chow diet were used to address the role of CLK2 in the hypothalamus. RESULTS: Hypothalamic CLK2(Thr343) phosphorylation, which induces CLK2 activity, is regulated in vivo by refeeding, insulin and leptin, in a PI3K dependent manner...
October 13, 2016: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Helena C Cesar, Luciana Pellegrini Pisani
A high-fat diet is the main environmental cue that has been studied in the hypothalamus since the discovery of its connection with hypothalamic inflammation. Current evidence shows hypothalamic inflammation as a likely mechanism for the dysregulation on the homeostatic control of energy balance, which leads to metabolic alterations and obesity. Although this mechanism seems to be reversible when set during adulthood, we argue whether dietary fatty acids, during critical periods of development, could affect hypothalamic function permanently and set an increased susceptibility to obesity...
September 13, 2016: Journal of Nutritional Biochemistry
Cinthia García-Luna, Paulina Soberanes-Chavez, Patricia de Gortari
Feeding patterns are important factors in obesity evolvement. Time-restricted feeding schedules (tRF) during resting phase change energy homeostasis regulation, disrupting the circadian release of metabolism-regulating hormones, such as leptin, insulin and corticosterone and promoting body weight gain. Thyroid (HPT) and adrenal (HPA) axes exhibit a circadian regulation and are involved in energy expenditure, thus studying their parameters in tRF paradigms will elucidate their role in energy homeostasis impairments under such conditions...
October 11, 2016: Journal of Endocrinology
Kristina Hofmann, Christian Lamberz, Kira Piotrowitz, Nina Offermann, Diana But, Anja Scheller, Ashraf Al-Amoudi, Lars Kuerschner
Although the brain controls all main metabolic pathways in the whole organism, its lipid metabolism is partially separated from the rest of the body. Circulating lipids and other metabolites are taken up into brain areas like the hypothalamus and are locally metabolized and sensed involving several hypothalamic cell types. In this study we show that saturated and unsaturated fatty acids are differentially processed in the murine hypothalamus. The observed differences involve both lipid distribution and metabolism...
October 11, 2016: Glia
Jun Udagawa, Kodai Hino
Epidemiological studies suggest that exposure to prenatal stressors, including malnutrition, maternal immune activation (MIA), and adverse life events, is associated with increased risks of schizophrenia, autism spectrum disorder (ASD), and attention-deficit hyperactivity disorder (ADHD). However, the underlying pathophysiological mechanisms are unclear. The first trimester of pregnancy is particularly a vulnerable period. During this period, the self-renewal of neural stem cells and neurogenesis vigorously occur, and synaptic connections are partially formed in the telencephalon...
2016: Nihon Eiseigaku Zasshi. Japanese Journal of Hygiene
Lionel Carneiro, Sarah Geller, Audrey Hébert, Cendrine Repond, Xavier Fioramonti, Corinne Leloup, Luc Pellerin
Ketone bodies have been shown to transiently stimulate food intake and modify energy homeostasis regulatory systems following cerebral infusion for a moderate period of time (<6 hours). As ketone bodies are usually enhanced during episodes of fasting, this effect might correspond to a physiological regulation. In contrast, ketone bodies levels remain elevated for prolonged periods during obesity, and thus could play an important role in the development of this pathology. In order to understand this transition, ketone bodies were infused through a catheter inserted in the carotid to directly stimulate the brain for a period of 24 hours...
October 6, 2016: Scientific Reports
B Paolini, P E Maltese, I Del Ciondolo, D Tavian, S Missaglia, C Ciuoli, M Zuntini, S Cecchin, M Bertelli, G Pompucci
Obesity is a major public health concern; despite evidence of high heritability, the genetic causes of obesity remain unclear. In this study, we assessed the presence of mutations in three genes involved in the hypothalamic leptin-melanocortin regulation pathway (leptin, LEP; leptin receptor, LEPR; and melanocortin-4 receptor, MC4R), which is important for energy homeostasis in the body, in a group of patients with severe obesity. For this study, we selected 77 patients who had undergone bariatric surgery and had a pre-operative body mass index (BMI) >35 kg/m(2), early onset and a family history of being overweight...
August 19, 2016: Genetics and Molecular Research: GMR
Kavaljit H Chhabra, Jessica M Adams, Graham L Jones, Miho Yamashita, Martin Schlapschy, Arne Skerra, Marcelo Rubinstein, Malcolm J Low
OBJECTIVE: A major challenge for obesity treatment is the maintenance of reduced body weight. Diet-induced obese mice are resistant to achieving normoweight once the obesogenic conditions are reversed, in part because lowered circulating leptin leads to a reduction in metabolic rate and a rebound of hyperphagia that defend the previously elevated body weight set point. Because hypothalamic POMC is a central leptin target, we investigated whether changes in circulating leptin modify Pomc expression to maintain normal energy balance in genetically predisposed obese mice...
October 2016: Molecular Metabolism
Soledad Pitra, Yumei Feng, Javier E Stern
BACKGROUND: Hypertension and obesity are highly interrelated diseases, being critical components of the metabolic syndrome. Despite the growing prevalence of this syndrome in the world population, efficient therapies are still missing. Thus, identification of novel targets and therapies are warranted. An enhanced activity of the hypothalamic renin-angiotensin system (RAS), including the recently discovered prorenin (PR) and its receptor (PRR), has been implicated as a common mechanism underlying aberrant sympatho-humoral activation that contributes to both metabolic and cardiovascular dysregulation in the metabolic syndrome...
October 2016: Molecular Metabolism
Martin J T Kalsbeek, Laurie Mulder, Chun-Xia Yi
Microglia are the resident macrophages of the CNS, and are in charge of maintaining a healthy microenvironment to ensure neuronal survival. Microglia carry out a non-stop patrol of the CNS, make contact with neurons and look for abnormalities, all of which requires a vast amount of energy. This non-signaling energy demand increases after activation by pathogens, neuronal damage or other kinds of stimulation. Of the three major energy substrates - glucose, fatty acids and glutamine - glucose is crucial for microglia survival and several glucose transporters are expressed to supply sufficient glucose influx...
September 28, 2016: Molecular and Cellular Endocrinology
Anthe S Sterkenburg, Anika Hoffmann, Julia Reichel, Kristin Lohle, Maria Eveslage, Monika Warmuth-Metz, Hermann L Müller
CONTEXT: Hypothalamic obesity, cardiovascular disease (CVD), and relapse/progression have major impact on prognosis in childhood-onset craniopharyngioma (CP). We analyzed nuchal skinfold thickness (NST) on magnetic resonance imaging (MRI) performed for follow-up monitoring as a novel parameter for body composition (BC) and CVD in CP. OBJECTIVE: Identify association of NST with body mass index (BMI), waist-to-height ratio (WHtR), functional capacity, and blood pressure (BP) in CP and controls...
September 28, 2016: Journal of Clinical Endocrinology and Metabolism
Yuhuan Meng, Yujia Guan, Wenlu Zhang, Yu-E Wu, Huanhuan Jia, Yu Zhang, Xiuqing Zhang, Hongli Du, Xiaoning Wang
The Goto-Kakizaki (GK) rat is an animal model of non-obese type 2 diabetes (T2D). The GK rat was generated through the introduction of various genetic mutations from continuous inbreeding; these rats develop diabetes spontaneously. The mutated genes in GK rats may play key roles in the regulation of diabetes. The hypothalamus plays a central role in systematic energy homeostasis. Here, the hypothalamic transcriptomes in GK and Wistar rats at 4, 8 and 12 weeks were investigated by RNA-seq, and multiple variants and gene expression profiles were obtained...
September 28, 2016: Scientific Reports
M Ibars, A Ardid-Ruiz, M Suárez, B Muguerza, C Bladé, G Aragonès
OBJECTIVE: Dietary obesity is usually linked with hypothalamic leptin resistance, in which the primary impact is an interference in the homeostatic control of body weight and appetite. Notably, proanthocyanidins (PACs), which are the most abundant phenolic compounds present in human diet, modulate adiposity and food intake. The aim of this study was to assess whether PACs could re-establish appropriate leptin signalling in both the hypothalamus and peripheral tissues. DESIGN: Male Wistar rats were fed either a standard chow diet (STD group, n=7) or a cafeteria diet (CD) for 13 weeks...
October 18, 2016: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Luba Sominsky, Ilvana Ziko, Thai-Xinh Nguyen, Zane B Andrews, Sarah J Spencer
Early life overweight is a significant risk factor for developmental programming of adult obesity due to changes in the availability of metabolic factors crucial for the maturation of brain appetite-regulatory circuitry. The appetite-stimulating hormone, ghrelin, has been recently identified as a major regulator of the establishment of hypothalamic feeding pathways. Ghrelin exists in circulation in two major forms, as acylated and des-acylated ghrelin. While most research has focused on acyl ghrelin, the role of neonatal des-acyl ghrelin in metabolic programming is currently unknown...
September 23, 2016: Neuropharmacology
Charlotte Sefton, Erika Harno, Alison Davies, Helen Small, Tiffany-Jayne Allen, Jonathan R Wray, Catherine B Lawrence, Anthony P Coll, Anne White
Glucocorticoid (Gc) excess, from endogenous overproduction in disorders of the hypothalamic-pituitary-adrenal axis or exogenous medical therapy, is recognised to cause adverse metabolic side effects. The Gc receptor (GR) is widely expressed throughout the body, including brain regions such as the hypothalamus. However the extent to which chronic Gcs affect Gc concentrations in the hypothalamus and impact on GR and target genes is unknown. To investigate this, we used a murine model of corticosterone-induced obesity, and analysed corticosterone levels in the hypothalamus and expression of genes relevant to Gc action...
September 20, 2016: Endocrinology
Inês Pinto, Simon Wilkinson, Daniel Virella, Marta Alves, Conceição Calhau, Rui Coelho
INTRODUCTION: Quality of the parent-infant relationship influences the mechanisms of development of the child's physiological stress regulation. This study explored associations between attachment strategies and both cortisol and thyroid stimulating hormone, hypothesized to be respectively a potential mediator and a potential intervening variable of the mother-child relationship in obese children. MATERIAL AND METHODS: A sample of 83 obese children (46 boys), aged 10...
May 2016: Acta Médica Portuguesa
Judit Tenk, Ildikó Rostás, Nóra Füredi, Alexandra Mikó, Szilvia Soós, Margit Solymár, Balázs Gaszner, Miklós Székely, Erika Pétervári, Márta Balaskó
Previously demonstrated age-related changes in the catabolic melanocortin system that may contribute to middle-aged obesity and aging anorexia, raise the question of the potential involvement of corticotropin-releasing factor (CRF) in these phenomena, as this catabolic hypothalamic mediator acts downstream to melanocortins. Catabolic effects of CRF were shown to be mediated by both CRF1 (hypermetabolism) and CRF2 (anorexia) receptors. To test the potential role of CRF in age-related obesity and aging anorexia, we investigated acute central effects of the peptide on energy balance in male and female rats during the course of aging...
September 13, 2016: Peptides
Cristina Contreras, Ismael González-García, Patricia Seoane-Collazo, Noelia Martínez-Sánchez, Laura Liñares-Pose, Eva Rial-Pensado, Johan Fernø, Manuel Tena-Sempere, Núria Casals, Carlos Diéguez, Rubén Nogueiras, Miguel López
The chaperone GRP78/BiP (glucose regulated protein 78 kDa/binding immunoglobulin protein) modulates protein folding in reply to cellular insults that lead to ER stress. The aim of this study was to investigate the role of hypothalamic GRP78 on energy balance, with particular interest on thermogenesis and browning of white adipose tissue (WAT). For this purpose, we used diet-induced obese rats and thapsigargin-treated rats and by combining metabolic, histologic, physiologic, pharmacologic, thermographic and molecular techniques, we studied the effect of genetic manipulation of hypothalamic GRP78...
September 15, 2016: Diabetes
María F Andreoli, Cora Stoker, María F Rossetti, Gisela P Lazzarino, Enrique H Luque, Jorge G Ramos
Removing dietary phytoestrogens causes obesity and diabetes in adult male rats. Based on the facts that hypothalamic food intake control is disrupted in phytoestrogen-deprived animals and that several steroids affect food intake, we hypothesized that phytoestrogen withdrawal alters the expression of hypothalamic steroidogenic enzymes. Male Wistar rats fed with a high-phytoestrogen diet from conception to adulthood were subjected to phytoestrogen withdrawal by feeding them a low-phytoestrogen diet or a high-phytoestrogen, high-fat diet...
September 2016: Nutrition Research
Miranda D Johnson, Sebastien G Bouret, Ambrose A Dunn-Meynell, Christina Neuner Boyle, Thomas A Lutz, Barry E Levin
Selectively bred diet-induced obese (DIO) rats become obese on a high fat diet and are leptin resistant before becoming obese. As compared to diet-resistant (DR) neonates, DIO neonates have impaired leptin-dependent arcuate (ARC) neuropeptide Y/agouti-related peptide (NPY/AgRP) and α-melanocyte-stimulating hormone (αMSH; from pro-opiomelanocortin (POMC) neurons) axon outgrowth to the paraventricular nucleus (PVN). Using phosphorylation of STAT3 (pSTAT3) as a surrogate, we show that reduced DIO ARC leptin signaling develops by postnatal day 7 (P7) and is reduced within POMC, but not NPY/AgRP neurons...
September 14, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
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