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Hypothalamus in weight loss

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https://www.readbyqxmd.com/read/28628102/regulation-of-body-weight-and-energy-homeostasis-by-neuronal-cell-adhesion-molecule-1
#1
Thomas Rathjen, Xin Yan, Natalia L Kononenko, Min-Chi Ku, Kun Song, Leiron Ferrarese, Valentina Tarallo, Dmytro Puchkov, Gaga Kochlamazashvili, Sebastian Brachs, Luis Varela, Klara Szigeti-Buck, Chun-Xia Yi, Sonja C Schriever, Sudhir Gopal Tattikota, Anne Sophie Carlo, Mirko Moroni, Jan Siemens, Arnd Heuser, Louise van der Weyden, Andreas L Birkenfeld, Thoralf Niendorf, James F A Poulet, Tamas L Horvath, Matthias H Tschöp, Matthias Heinig, Mirko Trajkovski, Volker Haucke, Matthew N Poy
Susceptibility to obesity is linked to genes regulating neurotransmission, pancreatic beta-cell function and energy homeostasis. Genome-wide association studies have identified associations between body mass index and two loci near cell adhesion molecule 1 (CADM1) and cell adhesion molecule 2 (CADM2), which encode membrane proteins that mediate synaptic assembly. We found that these respective risk variants associate with increased CADM1 and CADM2 expression in the hypothalamus of human subjects. Expression of both genes was elevated in obese mice, and induction of Cadm1 in excitatory neurons facilitated weight gain while exacerbating energy expenditure...
June 19, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28620314/orexin-system-the-key-for-a-healthy-life
#2
REVIEW
Sergio Chieffi, Marco Carotenuto, Vincenzo Monda, Anna Valenzano, Ines Villano, Francesco Precenzano, Domenico Tafuri, Monica Salerno, Nicola Filippi, Francesco Nuccio, Maria Ruberto, Vincenzo De Luca, Luigi Cipolloni, Giuseppe Cibelli, Maria P Mollica, Diego Iacono, Ersilia Nigro, Marcellino Monda, Giovanni Messina, Antonietta Messina
The orexin-A/hypocretin-1 and orexin-B/hypocretin-2 are neuropeptides synthesized by a cluster of neurons in the lateral hypothalamus and perifornical area. Orexin neurons receive a variety of signals related to environmental, physiological and emotional stimuli, and project broadly to the entire CNS. Orexin neurons are "multi-tasking" neurons regulating a set of vital body functions, including sleep/wake states, feeding behavior, energy homeostasis, reward systems, cognition and mood. Furthermore, a dysfunction of orexinergic system may underlie different pathological conditions...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28588096/cns-%C3%AE-3-adrenergic-receptor-activation-regulates-feeding-behavior-white-fat-browning-and-body-weight
#3
Jennifer E Richard, Lorena López-Ferreras, Belén Chanclón, Kim Eerola, Peter Micallef, Karolina P Skibicka, Ingrid Wernstedt Asterholm
Pharmacological β3-adrenergic receptor (β3AR) activation leads to increased mitochondrial biogenesis and activity in white adipose tissue (WAT), a process commonly referred to as "browning", and transiently increased insulin release. These effects are associated with improved metabolic function and weight loss. It is assumed that this impact of β3AR agonists is mediated solely through activation of β3ARs in adipose tissue. However, β3ARs are also found in the brain, in areas such as the brainstem and hypothalamus that provide multisynaptic innervation to brown and white adipose depots...
June 6, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28580288/restoration-of-lepr-in-%C3%AE-cells-of-lepr-null-mice-does-not-prevent-hyperinsulinemia-and-hyperglycemia
#4
Anna M D'souza, Timothy J Kieffer
OBJECTIVE: The adipose-derived hormone leptin plays an important role in regulating body weight and glucose homeostasis. Leptin receptors are expressed in the central nervous system as well as peripheral tissues involved in regulating glucose homeostasis, including insulin-producing β cells of the pancreas. Previous studies assessing the role of leptin receptors in β cells used Cre-loxP to disrupt the leptin receptor gene (Lepr) in β cells, but variable results were obtained. Furthermore, recombination of Lepr was observed in the hypothalamus or exocrine pancreas, in addition to the β cells, and Lepr in non-β cells may have compensated for the loss of Lepr in β cells, thus making it difficult to assess the direct effects of Lepr in β cells...
June 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28579186/endocannabinoid-modulation-of-homeostatic-and-non-homeostatic-feeding-circuits
#5
REVIEW
Benjamin K Lau, Daniela Cota, Luigia Cristino, Stephanie L Borgland
The endocannabinoid system has emerged as a key player in the control of eating. Endocannabinoids, including 2-arachidonoylglycerol (2-AG) and anandamide (AEA), modulate neuronal activity via cannabinoid 1 receptors (CB1Rs) in multiple nuclei of the hypothalamus to induce or inhibit food intake depending on nutritional and hormonal status, suggesting that endocannabinoids may act in the hypothalamus to integrate different types of signals informing about the animal's energy needs. In the mesocorticolimbic system, (endo)cannabinoids modulate synaptic transmission to promote dopamine release in response to palatable food...
June 1, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28576837/hypothalamic-inflammation-in-human-obesity-is-mediated-by-environmental-and-genetic-factors
#6
Carina Kreutzer, Sönke Peters, Dominik M Schulte, Daniela Fangmann, Kathrin Türk, Stephan Wolff, Thilo van Eimeren, Markus Ahrens, Jan Beckmann, Clemens Schafmayer, Thomas Becker, Tina Kerby, Axel Rohr, Christian Riedel, Femke-Anouska Heinsen, Frauke Degenhardt, Andre Franke, Philip Rosenstiel, Nana Zubek, Christian Henning, Sandra Freitag-Wolf, Astrid Dempfle, Aristea Psilopanagioti, Helen Petrou-Papadaki, Lennart Lenk, Olav Jansen, Stefan Schreiber, Matthias Laudes
Obesity is associated with hypothalamic inflammation (HI) in animal models. In the present study we examined the mediobasal hypothalamus (MBH) of 57 obese human subjects and 54 age- and sex- matched non-obese controls by MRI and analyzed the T2-hyperintensity as a measure of HI. Obese subjects exhibited T2-hyperintensity in the left but not the right MBH which was strongly associated with systemic low-grade inflammation. MRI-spectroscopy revealed the number of neurons in the left hypothalamic region to be similar in obese versus control subjects suggesting functional but not structural impairment due to the inflammatory process...
June 2, 2017: Diabetes
https://www.readbyqxmd.com/read/28514514/alternation-between-short-and-long-photoperiod-reveals-hypothalamic-gene-regulation-linked-to-seasonal-body-weight-changes-in-djungarian-hamsters-phodopus-sungorus
#7
Jonathan H H Bank, Dana Wilson, Eddy Rijntjes, Perry Barrett, Annika Herwig
Djungarian hamsters are able to reduce their body weight by more than 30% in anticipation of the winter season. This particular adaptation to extreme environmental conditions is primarily driven by a natural reduction in day length and conserved under laboratory conditions. We used this animal model to investigate hypothalamic gene expression linked to body weight regulation behind this physiological phenomenon. After an initial collective short photoperiod (SP) adaptation for 14 weeks from a preceding long photoperiod (LP), hamsters were re-exposed to LP for either six or 14 weeks, followed by a second re-exposure to SP for eight weeks...
May 17, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28511934/repeated-manganese-administration-produced-abnormal-expression-of-circadian-clock-genes-in-the-hypothalamus-and-liver-of-rats
#8
Huan Li, Ximin Fan, Ying Luo, Sheng Song, Jie Liu, Qiyuan Fan
Manganese (Mn) neurotoxicity displays non-motor dysfunction and motor impairment like Parkinson's disease (PD), and is called as Manganism. Circadian disruption is a non-motor symptom found in PD and Manganism. Clock genes are essential to drive and maintain circadian rhythm, but little is known about Mn exposure on circadian clock genes expression. Both the brain and liver are targets of Mn, we hypothesize that repeated Mn administration could affect clock gene expression in the hypothalamus and livers. Male Sprague-Dawley rats were intraperitoneally injected Mn(2+) 1mg and 5mg/kg as MnCl2·4H2O, every other day for 30 days...
May 13, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28507313/chronic-intrahypothalamic-rather-than-subcutaneous-liraglutide-treatment-reduces-body-weight-gain-and-stimulates-the-melanocortin-receptor-system
#9
K Kaineder, T Birngruber, G Rauter, B Obermüller, J Eichler, J Münzker, W Al-Zoughbi, S I Mautner, S S Torekov, B Hartmann, P Kotzbeck, T R Pieber
BACKGROUND: The GLP-1 receptor agonist liraglutide is marketed for obesity treatment where it induces body weight reduction possibly via the hypothalamus, which regulates energy homeostasis. In animal studies, acute liraglutide treatment triggers satiety, weight loss and activates thermogenesis in adipose tissue. However, the precise mechanisms how liraglutide affects in particular chronic weight loss are still under investigation. OBJECTIVES: We aimed to evaluate whether chronic hypothalamic or chronic subcutaneous administration of liraglutide induces sustained weight loss through altered adipose tissue function and to what extent hypothalamic neuronal appetite regulators are involved in the liraglutide-induced weight loss in healthy lean rats on a normal diet...
April 25, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28487570/intranasal-insulin-enhances-brain-functional-connectivity-mediating-the-relationship-between-adiposity-and-subjective-feeling-of-hunger
#10
Stephanie Kullmann, Martin Heni, Ralf Veit, Klaus Scheffler, Jürgen Machann, Hans-Ulrich Häring, Andreas Fritsche, Hubert Preissl
Brain insulin sensitivity is an important link between metabolism and cognitive dysfunction. Intranasal insulin is a promising tool to investigate central insulin action in humans. We evaluated the acute effects of 160 U intranasal insulin on resting-state brain functional connectivity in healthy young adults. Twenty-five lean and twenty-two overweight and obese participants underwent functional magnetic resonance imaging, on two separate days, before and after intranasal insulin or placebo application. Insulin compared to placebo administration resulted in increased functional connectivity between the prefrontal regions of the default-mode network and the hippocampus as well as the hypothalamus...
May 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28466983/review-of-mechanisms-of-deoxynivalenol-induced-anorexia-the-role-of-gut-microbiota
#11
REVIEW
Zhao Peng, Liangkai Chen, Jie Xiao, Xiaoqi Zhou, Andreas K Nüssler, Liegang Liu, Jinping Liu, Wei Yang
Deoxynivalenol (DON) is one of the most important mycotoxins in cereal-based foods or other food productions, produced by Fusarium species. Because of the high occurrence of DON in food combined with vast consumption of cereals and grain worldwide, the DON-contaminated food is a very harmful factor for human and animal health. DON has been reported to induce anorexia at lower or chronic doses in animal models. However, further researches for DON-induced anorexia are limited. Previous publications demonstrated a close link between Bacteroidetes and Firmicutes, two kinds of gut microbiota, with weight loss and the effect of low administration of DON on neurotransmitters in the frontal cortex, cerebellum, hypothalamus, hippocampus and pons/medulla...
May 3, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/28326295/role-of-the-cytokine-like-hormone-leptin-in-muscle-bone-crosstalk-with-aging
#12
REVIEW
Mark W Hamrick
The cytokine-like hormone leptin is a classic adipokine that is secreted by adipocytes, increases with weight gain, and decreases with weight loss. Additional studies have, however, shown that leptin is also produced by skeletal muscle, and leptin receptors are abundant in both skeletal muscle and bone-derived mesenchymal (stromal) stem cells. These findings suggest that leptin may play an important role in muscle-bone crosstalk. Leptin treatment in vitro increases the expression of myogenic genes in primary myoblasts, and leptin treatment in vivo increases the expression of microRNAs involved in myogenesis...
February 2017: Journal of Bone Metabolism
https://www.readbyqxmd.com/read/28324017/a-novel-selective-bombesin-receptor-subtype-3-agonist-promotes-weight-loss-in-male-diet-induced-obese-rats-with-circadian-rhythm-change
#13
Yasunori Nio, Natsu Hotta, Minoru Maruyama, Kenichi Hamagami, Toshimi Nagi, Masaaki Funata, Junichi Sakamoto, Masanori Nakakariya, Nobuyuki Amano, Tomohiro Okawa, Yasuyoshi Arikawa, Shinobu Sasaki, Shoki Okuda, Shizuo Kasai, Yugo Habata, Yasutaka Nagisa
Bombesin receptor subtype 3 (BRS-3) is an orphan G-protein-coupled receptor. Based on the obese phenotype of male BRS-3-deficient mice, BRS-3 has been considered an attractive target for obesity treatment. Here, we developed a novel selective BRS-3 agonist (Compound-A) and evaluated its anti-obesity effects. Compound-A showed anorectic effects and enhanced energy expenditure in diet-induced obese (DIO)-F344 rats. Moreover, repeated oral administration of Compound-A for 7 days resulted in a significant body weight reduction in DIO-F344 rats...
March 16, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323920/perinatal-exposure-to-low-dose-bisphenol-a-disrupts-the-structural-and-functional-development-of-the-hypothalamic-feeding-circuitry
#14
Harry MacKay, Zachary R Patterson, Alfonso Abizaid
Bisphenol-A (BPA) is a component of polycarbonate and other plastics to which humans are regularly exposed at low levels. BPA is characterized as an endocrine disruptor because of observations of its estrogenic activity in various experimental models. We have previously shown evidence of disrupted hypothalamic feeding circuitry and leptin sensitivity in adult BPA-exposed animals subjected to a high-fat diet, but because these animals were already exhibiting a diet-induced obese phenotype, we could not rule out the possibility that these observations were simply consequences of the obesity, not a preexisting phenotype produced by BPA exposure...
April 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28301916/a-role-of-central-nell2-in-the-regulation-of-feeding-behavior-in-rats
#15
Jin Kwon Jeong, Jae Geun Kim, Han Rae Kim, Tae Hwan Lee, Jeong Woo Park, Byung Ju Lee
A brain-enriched secreting signal peptide, NELL2, has been suggested to play multiple roles in the development, survival, and activity of neurons in mammal. We investigated here a possible involvement of central NELL2 in regulating feeding behavior and metabolism. In situ hybridization and an im-munohistochemical approach were used to determine expression of NELL2 as well as its colocalization with proopiomelanocortin (POMC) and neuropeptide Y (NPY) in the rat hypothalamus. To investigate the effect of NELL2 on feeding behavior, 2 nmole of antisense NELL2 oligodeoxynucleotide was administered into the lateral ventricle of adult male rat brains for 6 consecutive days, and changes in daily body weight, food, and water intake were monitored...
March 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28291683/a-pegylated-analog-of-short-length-neuromedin-u-with-potent-anorectic-and-anti-obesity-effects
#16
Hiroshi Inooka, Kotaro Sakamoto, Tokuyuki Shinohara, Yasushi Masuda, Michiko Terada, Satoshi Kumano, Kotaro Yokoyama, Jiro Noguchi, Naoki Nishizawa, Hidenori Kamiguchi, Hisashi Fujita, Taiji Asami, Shiro Takekawa, Tetsuya Ohtaki
Neuromedin U (NMU) is a neuropeptide known to regulate food intake and energy homeostasis that is widely distributed in the gastrointestinal tract, hypothalamus, and pituitary. A short form of NMU, porcine NMU-8 has potent agonist activity for the receptors NMUR1 and NMUR2; however, its short half-life precludes its effective use in vivo. To address this limitation, we designed and synthesized NMU-8 analogs modified by polyethylene glycol (PEG) with a molecular weight of 30kDa (PEG30k) via a variety of linkers (i...
February 21, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28261955/a-randomized-placebo-controlled-trial-of-beloranib-for-the-treatment-of-hypothalamic-injury-associated-obesity
#17
Ashley Shoemaker, Joseph Proietto, M Jennifer Abuzzahab, Tania Markovic, Jaret Malloy, Dennis D Kim
AIMS: Hypothalamic injury-associated obesity (HIAO) results from damage to the hypothalamus that often occurs with surgical removal/radiation therapy of tumours in the hypothalamic region, such as craniopharyngioma. There is currently no rigorously studied pharmaceutical treatment for the intractable weight gain and cardiometabolic consequences that occur in patients with HIAO. We aimed to assess efficacy, safety and tolerability of beloranib treatment for 4 to 8 weeks in patients with HIAO...
March 6, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28242830/suppressed-sympathetic-outflow-to-skeletal-muscle-muscle-thermogenesis-and-activity-energy-expenditure-with-calorie-restriction
#18
Tariq I Almundarij, Chaitanya K Gavini, Colleen M Novak
During weight loss, adaptive thermogenesis occurs where energy expenditure (EE) is suppressed beyond that predicted for the smaller body size. Here, we investigated the contributions of resting and nonresting EE to the reduced total EE seen after 3 weeks of 50% calorie restriction (CR) in rats, focusing on activity-associated EE, muscle thermogenesis, and sympathetic outflow. Prolonged food restriction resulted in a 42% reduction in daily EE, through a 40% decrease in resting EE, and a 48% decline in nonresting EE These decreases in EE were significant even when the reductions in body weight and lean mass were taken into account...
February 2017: Physiological Reports
https://www.readbyqxmd.com/read/28192820/estrogen-maintains-skeletal-muscle-in-septic-rats-associated-with-altering-hypothalamic-inflammation-and-neuropeptides
#19
Chenyan Zhao, Jun Li, Minhua Cheng, Jialing Shi, Juanhong Shen, Tao Gao, Fengchan Xi, Wenkui Yu
Muscle wasting is one of the main contributors to the worse outcomes in sepsis. Whether estrogen could alleviate muscle wasting induced by sepsis remains unclear. This study was designed to test the effect of estrogen on muscle wasting and its relationship with central alteration in sepsis. Thirty Sprague-Dawley rats were divided into 3 groups: control group, sepsis group, and estrogen treated sepsis group. Animals were intraperitoneally injected with lipopolysaccharide (10 mg/kg) or saline, followed by subcutaneous injection of 17β-estradiol (1 mg/kg) or saline...
March 2017: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/28093506/the-tyrosine-kinase-receptor-tyro3-enhances-lifespan-and-neuropeptide-y-npy-neuron-survival-in-the-mouse-anorexia-anx-mutation
#20
Dennis Y Kim, Joanna Yu, Ryan K Mui, Rieko Niibori, Hamza Bin Taufique, Rukhsana Aslam, John W Semple, Sabine P Cordes
Severe appetite and weight loss define the eating disorder anorexia nervosa, and can also accompany the progression of some neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS). Although acute loss of hypothalamic neurons that produce appetite-stimulating neuropeptide Y (Npy) and agouti-related peptide (Agrp) in adult mice or in mice homozygous for the anorexia (anx) mutation causes aphagia, our understanding of the factors that help maintain appetite regulatory circuitry is limited. Here we identify a mutation (C19T) that converts an arginine to a tryptophan (R7W) in the TYRO3 protein tyrosine kinase 3 (Tyro3) gene, which resides within the anx critical interval, as contributing to the severity of anx phenotypes...
May 1, 2017: Disease Models & Mechanisms
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