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Hypothalamus in weight loss

Cong Ming-Hua, Zou Bao-Hua, Yu Lei
Anorexia cancer cachexia syndrome is prevalent in advanced cancer patients, which is featured by anorexia, decreased dietary intake, body weight loss (skeletal muscle mass loss), and unable to be reversed by routine nutritional support therapy. Up to now, the main mechanisms involved in cancer cachexia include excessive systemic inflammation, which is represented by increased plasma levels of IL-1, IL-6, TNF-alpha, tumor-induced factors, such as PIF and LMF. These factors eventually act on orexigenic and anorexigenic neurons located in hypothalamus or protein and lipid metabolism of peripheral tissues, which lead to anorexia, decreased dietary intake, enhanced basic metabolism rate and hyper catabolism...
October 18, 2016: Current Pharmaceutical Biotechnology
Katharine F Hunt, Joel T Dunn, Carel W le Roux, Laurence J Reed, Paul K Marsden, Ameet G Patel, Stephanie A Amiel
OBJECTIVE: Improved appetite control, possibly mediated by exaggerated gut peptide responses to eating, may contribute to weight loss after Roux-en-Y gastric bypass (RYGB). This study compared brain responses to food ingestion between post-RYGB (RYGB), normal weight (NW), and obese (Ob) unoperated subjects and explored the role of gut peptide responses in RYGB. RESEARCH DESIGN AND METHODS: Neuroimaging with [(18)F]-fluorodeoxyglucose (FDG) positron emission tomography was performed in 12 NW, 21 Ob, and 9 RYGB (18 ± 13 months postsurgery) subjects after an overnight fast, once FED (400 kcal mixed meal), and once FASTED, in random order...
October 2016: Diabetes Care
Helene Johannessen, David Revesz, Yosuke Kodama, Nikki Cassie, Karolina Skibicka, Perry Barrett, Suzanne Dickson, Jens Holst, Jens Rehfeld, Geoffrey van der Plasse, Roger Adan, Bård Kulseng, Elinor Ben-Menachem, Chun-Mei Zhao, Duan Chen
BACKGROUND: Recently, the US FDA has approved "vagal blocking therapy or vBLoc® therapy" as a new treatment for obesity. The aim of the present study was to study the mechanism-of-action of "VBLOC" in rat models. METHODS: Rats were implanted with VBLOC, an intra-abdominal electrical device with leads placed around gastric vagal trunks through an abdominal incision and controlled by wireless device. Body weight, food intake, hunger/satiety, and metabolic parameters were monitored by a comprehensive laboratory animal monitoring system...
August 30, 2016: Obesity Surgery
W Xu, K Liu, Q T Lin, X J Ye, Y Lu, X X Zhang, L C Zhao, H C Gao, Z H Yan
OBJECTIVE: To establish and evaluate a rat model of diabetes comorbid depression, and observe alterations in expression of glial fibrillary acidic protein (GFAP) in several cerebral regions. METHODS: Eighteen Wistar rats were randomly divided into three groups, the control group (group CON, n=6), the diabetes mellitus group (group DM, n=6), and the diabetes comorbid depression group (group DD, n=6). Rats of group DM and group DD were injected intraperitoneally with STZ (64 mg/kg), the control rats received sham injections of citrate buffer alone...
August 2, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Jean-Baptiste Cavin, Eglantine Voitellier, Françoise Cluzeaud, Nathalie Kapel, Jean-Pierre Marmuse, Jean-Marc Chevallier, Simon Msika, André Bado, Maude Le Gall
The technically easier one-anastomosis (mini) gastric bypass (MGB) is associated with similar metabolic improvements and weight loss as the Roux-en-Y gastric bypass (RYGB). However, MGB is controversial and suspected to result in greater malabsorption than RYGB. In this study, we compared macronutrient absorption and intestinal adaptation after MGB or RYGB in rats. Body weight and food intake were monitored and glucose tolerance tests were performed in rats subjected to MGB, RYGB, or sham surgery. Carbohydrate, protein, and lipid absorption was determined by fecal analyses...
September 1, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
Shin J Lee, Katharina Diener, Sharon Kaufman, Jean-Philippe Krieger, Klaus G Pettersen, Nino Jejelava, Myrtha Arnold, Alan G Watts, Wolfgang Langhans
OBJECTIVE: Glucagon-like peptide-1 (GLP-1) analogs are attractive options for the treatment of type II diabetes and obesity because of their incretin and anorexigenic effects. Peripheral administration of the GLP-1R agonist Exendin-4 (Ex-4) also increases glucocorticoid secretion in rodents and humans, but whether the released glucocorticoids interact with Ex-4's anorexigenic effect remains unclear. METHODS: To test this, we used two experimental approaches that suppress corticosterone secretion and then assessed Ex-4 effects on eating in adult male rats...
July 2016: Molecular Metabolism
Sungho Jin, Jae Geun Kim, Jeong Woo Park, Marco Koch, Tamas L Horvath, Byung Ju Lee
Various pathophysiologic mechanisms leading to sickness behaviors have been proposed. For example, an inflammatory process in the hypothalamus has been implicated, but the signaling modalities that involve inflammatory mechanisms and neuronal circuit functions are ill-defined. Here, we show that toll-like receptor 2 (TLR2) activation by intracerebroventricular injection of its ligand, Pam3CSK4, triggered hypothalamic inflammation and activation of arcuate nucleus microglia, resulting in altered input organization and increased activity of proopiomelanocortin (POMC) neurons...
2016: Scientific Reports
J Ceccarini, N Weltens, H G Ly, J Tack, L Van Oudenhove, K Van Laere
Although of great public health relevance, the mechanisms underlying disordered eating behavior and body weight regulation remain insufficiently understood. Compelling preclinical evidence corroborates a critical role of the endocannabinoid system (ECS) in the central regulation of appetite and food intake. However, in vivo human evidence on ECS functioning in brain circuits involved in food intake regulation as well as its relationship with body weight is lacking, both in health and disease. Here, we measured cannabinoid 1 receptor (CB1R) availability using positron emission tomography (PET) with [(18)F]MK-9470 in 54 patients with food intake disorders (FID) covering a wide body mass index (BMI) range (anorexia nervosa, bulimia nervosa, functional dyspepsia with weight loss and obesity; BMI range=12...
2016: Translational Psychiatry
Julia Ferrari Carneiro Teixeira, Priscila Dos Santos Maia-Lemos, Mônica Dos Santos Cypriano, Luciana Pellegrini Pisani
PURPOSE: Obesity is a late effect in survivors of childhood cancer and correlates with chronic complications. Survivors of leukemia, brain tumors, and hematopoietic stem cell transplantation are more likely to develop obesity resulting from treatment modalities such as radiotherapy and glucocorticoids. This paper analyzes and integrates the current data available to health professionals in order to clarify strategies that can be used to treat and prevent obesity in childhood cancer survivors...
June 18, 2016: Jornal de Pediatria
Lotte Bjerre Knudsen, Anna Secher, Jacob Hecksher-Sørensen, Charles Pyke
Liraglutide is a glucagon-like peptide-1 receptor (GLP-1R) agonist marketed for the treatment of type 2 diabetes. Besides lowering blood glucose, liraglutide reduces bodyweight, and has recently also been approved for the obesity indication. Acutely, GLP-1 markedly reduces gastric emptying, and this effect was previously believed to at least partly explain the effect on bodyweight loss. However, recent studies in both humans and animals have shown that GLP-1R agonists, such as liraglutide, that lead to pharmacological concentrations for 24 h/day only have a minor effect on gastric emptying; such an effect is unlikely to have lasting effects on appetite reduction...
April 2016: Journal of Diabetes Investigation
Alexandros Tsompanidis, Elizabeth Vafiadaki, Susann Blüher, Georgia Kalozoumi, Despina Sanoudou, Christos S Mantzoros
INTRODUCTION: The Ciliary Neurotrophic Factor (CNTF) is a pluripotent cytokine with anorexigenic actions in the hypothalamus that improves insulin sensitivity, increases energy expenditure and induces weight loss. Since CNTF also has an established myotrophic role, we sought to examine whether skeletal muscle contributes to the CNTF-induced metabolic improvement and identify the molecular mechanisms mediating these effects. METHODS: We used a mouse model of diet-induced obesity, to which high or low CNTF doses were administered for 7days...
June 2016: Metabolism: Clinical and Experimental
Xun Cao, Xiao Zhou, Xiao-Min Liu, Li-Hong Zhou
Liraglutide, a human glucagon-like peptide (GLP1) analog that partially inhibits dipeptidyl-peptidase 4 (DPP4), can decrease glucose levels and suppress appetite in patients with type 2 diabetes (T2DM). GLP1 and its receptor (GLP1R) also exist in the taste buds of rodents and regulate taste sensitivity. DPP4, a protease, functions in homeostasis of blood glucose, lipids, and body weight. Interactions among GLP1, GLP1R, and DPP4 likely affect taste and food-intake behavior. The aim of the present study was to investigate DPP4 expression in the taste buds of the circumvallate papillae (CV) in T2DM rats, and determine the effects of liraglutide treatment...
July 2016: Journal of Molecular Endocrinology
Marie Balslev Backe, Ingrid Wahl Moen, Christina Ellervik, Jakob Bondo Hansen, Thomas Mandrup-Poulsen
Dietary advice is the cornerstone in first-line treatment of metabolic diseases. Nutritional interventions directed at these clinical conditions mainly aim to (a) improve insulin resistance by reducing energy-dense macronutrient intake to obtain weight loss and (b) reduce fluctuations in insulin secretion through avoidance of rapidly absorbable carbohydrates. However, even in the majority of motivated patients selected for clinical trials, massive efforts using this approach have failed to achieve lasting efficacy...
July 17, 2016: Annual Review of Nutrition
Jonatan Kornholt
A 25-year-old previously healthy man developed secondary adrenal insufficiency during opiate treatment with tramadol and morphine for upper back pain. He experienced a 10 kg weight loss in six weeks. MRI of the hypothalamus and the pituitary gland ruled out cerebral pathology. After discontinuation of the opiate treatment the condition normalised. Opiate therapy can cause endocrine dysfunction, and clinicians should always consider adverse drug reactions as a differential diagnosis for unexplained symptoms.
April 25, 2016: Ugeskrift for Laeger
A Rodríguez, J Gómez-Ambrosi, V Catalán, S Ezquerro, L Méndez-Giménez, S Becerril, P Ibáñez, N Vila, M A Margall, R Moncada, V Valentí, C Silva, J Salvador, G Frühbeck
BACKGROUND/OBJECTIVES: Uroguanylin and guanylin are secreted by intestinal epithelial cells as prohormones postprandially and act on the hypothalamus to induce satiety. The impact of obesity and obesity-associated type 2 diabetes (T2D) on proguanylin and prouroguanylin expression/secretion as well as the potential role of guanylin and uroguanylin in the control of lipolysis in humans was evaluated. SUBJECTS/METHODS: Circulating and gastrointestinal expression of proguanylin (GUCA2A) and prouroguanylin (GUCA2B) were measured in 134 subjects...
September 2016: International Journal of Obesity: Journal of the International Association for the Study of Obesity
J Antonio González, Panagiota Iordanidou, Molly Strom, Antoine Adamantidis, Denis Burdakov
The lateral hypothalamus (LH) controls energy balance. LH melanin-concentrating-hormone (MCH) and orexin/hypocretin (OH) neurons mediate energy accumulation and expenditure, respectively. MCH cells promote memory and appropriate stimulus-reward associations; their inactivation disrupts energy-optimal behaviour and causes weight loss. However, MCH cell dynamics during wakefulness are unknown, leaving it unclear if they differentially participate in brain activity during sensory processing. By fiberoptic recordings from molecularly defined populations of LH neurons in awake freely moving mice, we show that MCH neurons generate conditional population bursts...
2016: Nature Communications
J Melasch, M Rullmann, A Hilbert, J Luthardt, G A Becker, M Patt, M Stumvoll, M Blüher, A Villringer, K Arelin, P M Meyer, A Bresch, O Sabri, S Hesse, B Pleger
BACKGROUND/OBJECTIVES: The neurobiological mechanisms linking obesity to emotional distress related to weight remain largely unknown. PARTICIPANTS/METHODS: Here we combined positron emission tomography, using the serotonin transporter (5-HTT) radiotracer [(11)C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile, with functional connectivity magnetic resonance imaging, the Beck Depression Inventory (BDI-II) and the Impact of Weight on Quality of Life-Lite questionnaire (IWQOL-Lite) to investigate the role of central serotonin in the severity of depression (BDI-II), as well as in the loss of emotional well-being with body weight (IWQOL-Lite)...
August 2016: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Pauline Vercruysse, Jérôme Sinniger, Hajer El Oussini, Jelena Scekic-Zahirovic, Stéphane Dieterlé, Reinhard Dengler, Thomas Meyer, Stephan Zierz, Jan Kassubek, Wilhelm Fischer, Jens Dreyhaupt, Torsten Grehl, Andreas Hermann, Julian Grosskreutz, Anke Witting, Ludo Van Den Bosch, Odile Spreux-Varoquaux, Albert C Ludolph, Luc Dupuis
Amyotrophic lateral sclerosis, the most common adult-onset motor neuron disease, leads to death within 3 to 5 years after onset. Beyond progressive motor impairment, patients with amyotrophic lateral sclerosis suffer from major defects in energy metabolism, such as weight loss, which are well correlated with survival. Indeed, nutritional intervention targeting weight loss might improve survival of patients. However, the neural mechanisms underlying metabolic impairment in patients with amyotrophic lateral sclerosis remain elusive, in particular due to the lack of longitudinal studies...
April 2016: Brain: a Journal of Neurology
Deng-Fu Guo, Huxing Cui, Qihong Zhang, Donald A Morgan, Daniel R Thedens, Darryl Nishimura, Justin L Grobe, Val C Sheffield, Kamal Rahmouni
Bardet-Biedl syndrome (BBS) is a highly pleiotropic autosomal recessive disorder associated with a wide range of phenotypes including obesity. However, the underlying mechanism remains unclear. Here, we show that neuronal BBSome is a critical determinant of energy balance through its role in the regulation of the trafficking of the long signaling form of the leptin receptor (LRb). Targeted disruption of the BBSome by deleting the Bbs1 gene from the nervous system causes obesity in mice, and this phenotype is reproduced by ablation of the Bbs1 gene selectively in the LRb-expressing cells, but not from adipocytes...
February 2016: PLoS Genetics
Dhiraj G Kabra, Katrin Pfuhlmann, Cristina García-Cáceres, Sonja C Schriever, Veronica Casquero García, Adam Fiseha Kebede, Esther Fuente-Martin, Chitrang Trivedi, Kristy Heppner, N Henriette Uhlenhaut, Beata Legutko, Uma D Kabra, Yuanqing Gao, Chun-Xia Yi, Carmelo Quarta, Christoffer Clemmensen, Brian Finan, Timo D Müller, Carola W Meyer, Marcelo Paez-Pereda, Kerstin Stemmer, Stephen C Woods, Diego Perez-Tilve, Robert Schneider, Eric N Olson, Matthias H Tschöp, Paul T Pfluger
Hypothalamic leptin signalling has a key role in food intake and energy-balance control and is often impaired in obese individuals. Here we identify histone deacetylase 5 (HDAC5) as a regulator of leptin signalling and organismal energy balance. Global HDAC5 KO mice have increased food intake and greater diet-induced obesity when fed high-fat diet. Pharmacological and genetic inhibition of HDAC5 activity in the mediobasal hypothalamus increases food intake and modulates pathways implicated in leptin signalling...
2016: Nature Communications
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