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Hypothalamus in weight loss

Chloé Chrétien, Claire Fenech, Fabienne Liénard, Sylvie Grall, Charlène Chevalier, Sylvie Chaudy, Xavier Brenachot, Raymond Berges, Katie Louche, Romana Stark, Emmanuelle Nédélec, Amélie Laderrière, Zane B Andrews, Alexandre Benani, Veit Flockerzi, Jean Gascuel, Jana Hartmann, Cédric Moro, Lutz Birnbaumer, Corinne Leloup, Luc Pénicaud, Xavier Fioramonti
The medio-basal hypothalamus (MBH) contains neurons capable of directly detecting metabolic signals such as glucose to control energy homeostasis. Among them, glucose-excited (GE) neurons increase their electrical activity when glucose rises. In view of previous work, we hypothesized that Transient Receptor Potential Canonical type-3 (TRPC3) channels are involved in hypothalamic glucose detection and the control of energy homeostasis.To investigate the role of TRPC3, we used constitutive and conditional TRPC3-deficient mice models...
November 29, 2016: Diabetes
Tariq I Almundarij, Mark E Smyers, Addison Spriggs, Lydia A Heemstra, Lisa Beltz, Eric Dyne, Caitlyn Ridenour, Colleen M Novak
Melanocortin 4 receptor (MC4R) variants contribute to human obesity, and rats lacking functional MC4R (Mc4r(K314X/K314X)) are obese. We investigated the hypothesis that low energy expenditure (EE) and physical activity contribute to this obese phenotype in male rats, and determined whether lack of functional MC4R conferred protection from weight loss during 50% calorie restriction. Though Mc4r(K314X/K314X) rats showed low brown adipose Ucp1 expression and were less physically active than rats heterozygous for the mutation (Mc4r(+/K314X)) or wild-type (Mc4r(+/+)) rats, we found no evidence of lowered EE in Mc4r(K314X/K314X) rats once body weight was taken into account using covariance...
November 25, 2016: Scientific Reports
Farhana Naznin, Hideyuki Sakoda, Tadashi Okada, Hironobu Tsubouchi, T M Zaved Waise, Kenji Arakawa, Masamitsu Nakazato
Chronic inflammation in systemic organs, such as adipose tissue, nodose ganglion, hypothalamus, and skeletal muscles, is closely associated with obesity and diabetes mellitus. Because sodium glucose cotransporter 2 (SGLT2) inhibitors exert both anti-diabetic and anti-obesity effects by promoting urinary excretion of glucose and subsequent caloric loss, we investigated the effect of canagliflozin, an SGLT2 inhibitor, on obesity-induced inflammation in neural tissues and skeletal muscles of mice. High-fat diet (HFD)-fed male C57BL/6J mice were treated with canagliflozin for 8 weeks...
November 19, 2016: European Journal of Pharmacology
Ragitha Chruvattil, Shreya Banerjee, Sarmi Nath, Jatin Machhi, Gitika Kharkwal, Mange Ram Yadav, Sarita Gupta
Elevated levels of glucocorticoid, a steroid hormone released in response to stress, have been implicated in the pathophysiology of diabetes, which is now known to extend its effect on brain functions. Hence, we aimed to investigate the status of brain insulin signaling in response to dexamethasone (a synthetic glucocorticoid) treatment in female Charles Foster rat. This model exhibited pronounced hyperinsulinemia and glucose intolerance with loss in appetite and body weight. Immunoblotting of insulin receptor (INSR)-PI3kinase-AKT demonstrated reduced insulin signaling in hypothalamus but no change in hippocampus, cortex, and cerebellum in dexamethasone-treated rats as compared to vehicle-treated rats, signifying the diversity of distribution and function of insulin in different brain regions...
November 7, 2016: Molecular Neurobiology
Sang Tak Lee, Jong Cheol Lee, Jong Whi Kim, Soo Young Cho, Je Kyung Seong, Myeong Hee Moon
Comprehensive lipidomic profiling in three different brain tissues (cortex, hippocampus, and hypothalamus) of mouse with p53 deficiency was performed by nanoflow liquid chromatography-tandem mass spectrometry (nLC-MS/MS) and the profile was compared with that of the wild type. p53 gene is a well-known tumour suppressor that prevents genome mutations that can cause cancers. More than 300 lipids (among 455 identified species), including phospholipids (PLs), sphingolipids, ceramides (Cers), and triacylglycerols (TAGs) were quantitatively analysed by selective reaction monitoring (SRM) of nanoflow ultrahigh performance liquid chromatography-electrospray ionization-tandem mass spectrometry (nUPLC-ESI-MS/MS)...
November 7, 2016: Scientific Reports
Sriparna Ghosal, Amy E B Packard, Parinaz Mahbod, Jessica M McKlveen, Randy J Seeley, Brent Myers, Yvonne Ulrich-Lai, Eric P Smith, David A D'Alessio, James P Herman
Organismal stress initiates a tightly orchestrated set of responses involving complex physiological and neurocognitive systems. Here, we present evidence for glucagon-like peptide 1 (GLP-1) mediated paraventricular hypothalamic circuit coordinating the global stress response. The GLP-1 receptor (Glp1r) in mice was knocked down in neurons expressing single-minded 1 (Sim1), a transcription factor abundantly expressed in the paraventricular nucleus (PVN) of the hypothalamus. Mice with Sim1-mediated Glp1r knockdown had reduced hypothalamic-pituitary-adrenal (HPA) axis responses to both acute and chronic stress and were protected against weight loss associated with chronic stress...
November 3, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Ruth B S Harris, Bhavna N Desai
Previous studies have shown that very low dose infusions of leptin into the 3(rd) or the 4(th) ventricle alone have little effect on energy balance, but simultaneous low dose infusions cause rapid weight loss and increased phosphorylation of STAT3 (pSTAT3) in hypothalamic sites that express leptin receptors. Other studies show that injecting high doses leptin into the 4(th) ventricle inhibits food intake and weight gain. Therefore, we tested whether 4(th) ventricle leptin infusions that cause weight loss are associated with increased leptin signaling in the hypothalamus...
November 1, 2016: American Journal of Physiology. Endocrinology and Metabolism
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
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