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Hypothalamus in weight loss

Antonio A F De Salles, Daniel A N Barbosa, Fernando Fernandes, Julio Abucham, Debora M Nazato, Juliana D Oliveira, Abrão Cury, Alexandre Biasi, Ronaldo Rossi, Camila Lasagno, Priscila T Bueno, Renato H N Santos, Lucas P Damiani, Alessandra A Gorgulho
BACKGROUND: Human morbid obesity is increasing worldwide in an alarming way. The hypothalamus is known to mediate its mechanisms. Deep brain stimulation (DBS) of the ventromedial hypothalamus (VMH) may be an alternative to treat patients refractory to standard medical and surgical therapies. OBJECTIVE: To assess the safety, identify possible side effects, and to optimize stimulation parameters of continuous VMH-DBS. Additionally, this study aims to determine if continuous VMH-DBS will lead to weight loss by causing changes in body composition, basal metabolism, or food intake control...
March 12, 2018: Neurosurgery
Jun Xiang, Cuidong Bian, Xiaodong Wan, Qimin Zhang, Shengsong Huang, Denglong Wu
BACKGROUND: Obesity is a metabolic disease with a serious health burden in children and adults, and it induces a variety of conditions including subfecundity. Sleeve gastrectomy showed encouraging results in terms of weight loss and improve quality of life, and this study aimed to determine whether sleeve gastrectomy could reverse obesity-induced impaired fertility in male Sprague-Dawley rats. METHODS: After 16 weeks of a chow diet (CD) or a high-fat diet (HFD) challenge, rats on the HFD were given a sleeve gastrectomy or sham operation and then fed an HFD for another 8 weeks...
March 5, 2018: Obesity Surgery
Cécile Bétry, Stéphane Thobois, Martine Laville, Emmanuel Disse
Despite a better understanding of obesity pathophysiology, treating this disease remains a challenge. New therapeutic options are needed. Targeting the brain is a promising way, considering both the brain abnormalities in obesity and the effects of bariatric surgery on the gut-brain axis. Deep brain stimulation could be an alternative treatment for obesity since this safe and reversible neurosurgical procedure modulates neural circuits for therapeutic purposes. We aimed to provide a critical review of published clinical and preclinical studies in this field...
February 20, 2018: Obesity Research & Clinical Practice
L J Zallar, B J Tunstall, C T Richie, Y J Zhang, Z B You, E L Gardner, M Heilig, J Pickel, G F Koob, L F Vendruscolo, B K Harvey, L Leggio
BACKGROUND/OBJECTIVES: Ghrelin, a stomach-derived hormone implicated in numerous behaviors including feeding, reward, stress, and addictive behaviors, acts by binding to the growth hormone secretagogue receptor (GHSR). Here, we present the development, verification, and initial characterization of a novel GHSR knockout (KO) Wistar rat model created with CRISPR genome editing. METHODS: Using CRISPR/Cas9, we developed a GHSR KO in a Wistar background. Loss of GHSR mRNA expression was histologically verified using RNAscope in wild-type (WT; n = 2) and KO (n = 2) rats...
January 30, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Aygul Subkhangulova, Anna R Malik, Guido Hermey, Oliver Popp, Gunnar Dittmar, Thomas Rathjen, Matthew N Poy, Alexander Stumpf, Prateep Sanker Beed, Dietmar Schmitz, Tilman Breiderhoff, Thomas E Willnow
SORCS1 and SORCS3 are two related sorting receptors expressed in neurons of the arcuate nucleus of the hypothalamus. Using mouse models with individual or dual receptor deficiencies, we document a previously unknown function of these receptors in central control of metabolism. Specifically, SORCS1 and SORCS3 act as intracellular trafficking receptors for tropomyosin-related kinase B to attenuate signaling by brain-derived neurotrophic factor, a potent regulator of energy homeostasis. Loss of the joint action of SORCS1 and SORCS3 in mutant mice results in excessive production of the orexigenic neuropeptide agouti-related peptide and in a state of chronic energy excess characterized by enhanced food intake, decreased locomotor activity, diminished usage of lipids as metabolic fuel, and increased adiposity, albeit at overall reduced body weight...
February 12, 2018: EMBO Reports
Pauline Vercruysse, Didier Vieau, David Blum, Åsa Petersén, Luc Dupuis
Neurodegenerative diseases (NDDs) are disorders characterized by progressive deterioration of brain structure and function. Selective neuronal populations are affected leading to symptoms which are prominently motor in amyotrophic lateral sclerosis (ALS) or Huntington's disease (HD), or cognitive in Alzheimer's disease (AD) and fronto-temporal dementia (FTD). Besides the common existence of neuronal loss, NDDs are also associated with metabolic changes such as weight gain, weight loss, loss of fat mass, as well as with altered feeding behavior...
2018: Frontiers in Molecular Neuroscience
Mariana Schroeder, Yonat Drori, Yair J Ben-Efraim, Alon Chen
Consumption of a low calorie diet is the most common approach to lose weight. While generally effective at first, it is frequently followed by a relapse where the pre-diet weight is regained, and often exceeded. This pattern of repeated weight loss/regain is referred to as weight cycling and the resulting metabolic response varies greatly between individuals. OBJECTIVE: We attempted to address the issue of individual differences in the response to weight cycling in male mice. METHODS: We first exposed adult wild type mice to repeated cycles of high/low fat food...
February 1, 2018: Molecular Metabolism
Mario Bustos, Hara Berger, Zeina Carolina Hannoush, Alejandro Ayala, Rochelle Freire, Atil Yilmaz Kargi
Lymphocytic hypothalamitis (LHT) is a rare disease characterized by pituitary dysfunction, autonomic instability, metabolic disturbances, and neuropsychiatric disorders. We report the case of a 30-year-old man found to have LHT that progressed despite treatment with methylprednisolone and intravenous immunoglobulin (IVIG). A literature review was conducted to identify prior studies pertaining to LHT. Our patient presented with several weeks of fatigue, cold intolerance, weight loss, confusion, and headache...
February 1, 2018: Journal of the Endocrine Society
Sabine Frank-Podlech, Julia von Schnurbein, Ralf Veit, Martin Heni, Jürgen Machann, Jaana M Heinze, Stephanie Kullmann, Jaida Manzoor, Saqib Mahmood, Hans-Ulrich Häring, Hubert Preissl, Martin Wabitsch, Andreas Fritsche
OBJECTIVE: Human obesity is associated with impaired central insulin signaling, and in very rare cases, severe obesity can be caused by congenital leptin deficiency. In such patients, leptin replacement results in substantial weight loss and improvement in peripheral metabolism. RESEARCH DESIGN AND METHODS: In a leptin-deficient patient, we investigated the impact of leptin substitution on central insulin action, as quantified by changes in neuronal activity after intranasal insulin application...
January 24, 2018: Diabetes Care
Cristina Contreras, Marcos F Fondevila, Miguel López
The chaperone GRP78 (glucose related protein 78), also called BiP (binding immunoglobulin protein) is a key regulator of endoplasmic reticulum (ER) stress. We recently described that over-expression of GRP78 specifically in the ventromedial nucleus of the hypothalamus (VMH) releases hypothalamic ER stress in rodent obese models leading to weight loss, reduced hepatic steatosis and improved insulin and leptin sensitivity. The action of GRP78 is mediated by a feeding-independent mechanism involving increased sympathetic tone, augmented brown adipose tissue (BAT) thermogenesis and induction browning of white adipose tissue (WAT)...
December 20, 2017: Adipocyte
Hyunju Park, So-Hee Ahn, Yieun Jung, Joo Chun Yoon, Youn-Hee Choi
BACKGROUND/AIMS: Leptin is a hormone expressed by adipose tissue that regulates body energy homeostasis and weight loss by activating leptin receptors in the hypothalamus. Leptin receptors are also expressed in astrocytes. An anti-apoptosis effect of leptin in brain has recently been reported. However, the anti-apoptosis mechanism of leptin in the brain is unknown. METHODS: To investigate whether leptin exerts protective effects against glutamate-induced apoptosis in astrocytes, we performed cell viability assays and apoptosis assays using rat primary astrocytes...
2017: Cellular Physiology and Biochemistry
Farhana Naznin, Koji Toshinai, T M Zaved Waise, Tadashi Okada, Hideyuki Sakoda, Masamitsu Nakazato
High-fat diet (HFD)-induced metabolic inflammation in the central and peripheral organs contributes to the pathogenesis of obesity. Long-term HFD blunts signaling by ghrelin, a gastric-derived orexigenic peptide, in the vagal afferent nerve via a mechanism involving in situ activation of inflammation. This study was undertaken to investigate whether ghrelin resistance is associated with progressive development of metabolic inflammation. In mice, ghrelin's orexigenic activity was abolished 2-4 weeks after the commencement of HFD (60% of energy from fat), consistent with the timing of accumulation and activation of macrophages and microglia in the nodose ganglion and hypothalamus...
February 2018: Journal of Molecular Endocrinology
Xin Yan, Zhen Wang, Vanessa Schmidt, Anton Gauert, Thomas E Willnow, Matthias Heinig, Matthew N Poy
OBJECTIVE: Obesity is strongly linked to genes regulating neuronal signaling and function, implicating the central nervous system in the maintenance of body weight and energy metabolism. Genome-wide association studies identified significant associations between body mass index (BMI) and multiple loci near Cell adhesion molecule2 (CADM2), which encodes a mediator of synaptic signaling enriched in the brain. Here we sought to further understand the role of Cadm2 in the pathogenesis of hyperglycemia and weight gain...
February 2018: Molecular Metabolism
G I McNamara, H D J Creeth, D J Harrison, K E Tansey, R M Andrews, A R Isles, R M John
Depression and anxiety are the most common mental health conditions during pregnancy and can impair the normal development of mother-infant interactions. These adversities are associated with low birth weight and increased risk of behavioural disorders in children. We recently reported reduced expression of the imprinted gene PATERNALLY EXPRESSED GENE 3 (PEG3) in placenta of human infants born to depressed mothers. Expression of Peg3 in the brain has previously been linked maternal behaviour in rodents, at least in some studies, with mutant dams neglecting their pups...
February 1, 2018: Human Molecular Genetics
María J Barahona, Paula Llanos, Antonia Recabal, Kathleen Escobar-Acuña, Roberto Elizondo-Vega, Magdiel Salgado, Patricio Ordenes, Elena Uribe, Fernando J Sepúlveda, Ricardo C Araneda, María A García-Robles
Glucose is a key modulator of feeding behavior. By acting in peripheral tissues and in the central nervous system, it directly controls the secretion of hormones and neuropeptides and modulates the activity of the autonomic nervous system. GLUT2 is required for several glucoregulatory responses in the brain, including feeding behavior, and is localized in the hypothalamus and brainstem, which are the main centers that control this behavior. In the hypothalamus, GLUT2 has been detected in glial cells, known as tanycytes, which line the basal walls of the third ventricle (3V)...
March 2018: Glia
Michael R La Frano, Angelina Hernandez-Carretero, Natalie Weber, Kamil Borkowski, Theresa L Pedersen, Olivia Osborn, John W Newman
Bile acids (BAs) influence the metabolism of glucose, lipids, and energy expenditure. We hypothesized that BA concentrations and related gene expression would be altered in lean (low-fat diet fed; LFD) vs diet-induced obese (high-fat diet fed; HFD) groups of mice and that some detected changes would remain after weight loss in an HFD group switched to the LFD (SW). Taurine conjugates dominated the bile acid composition of the liver, epididymal white adipose tissue (eWAT), and hypothalamus, with the latter having lower levels (~95%, ~95%, and ~80%, respectively; P<...
October 2017: Nutrition Research
Xin Yan, Natalia L Kononenko, Annemarie Brüel, Jesper Skovhus Thomsen, Matthew N Poy
The central nervous system is widely known to exert control over our systemic physiology via several mechanisms including the regulation of skeletal metabolism. Neuronal circuits within the hypothalamus have been shown to impact bone mass via leptin-dependent and independent mechanisms; however, the full extent to which the brain controls bone homeostasis is not known. We previously identified cell adhesion molecule1 (Cadm1) as a regulator of body weight and energy homeostasis via its expression in multiple regions of the brain...
November 13, 2017: Calcified Tissue International
J Antonio González, Jochen H M Prehn
The mechanisms that link diet and body weight are not fully understood. A diet high in fat often leads to obesity, and this in part is the consequence of diet-induced injury to specific hypothalamic nuclei. It has been suggested that a diet high in fat leads to cell loss in the lateral hypothalamus, which contains specific populations of neurons that are essential for regulating energy homoeostasis; however, we do not know which cell types are affected by the diet. We studied the possibility that high-fat diet leads to a reduction in orexin-A/hypocretin-1 (Hcrt1) and/or melanin-concentrating hormone (MCH) immunoreactivity in the lateral hypothalamus...
January 15, 2018: Neuroscience
Andrew F Alalade, Elizabeth Ogando-Rivas, Jerome Boatey, Mark M Souweidane, Vijay K Anand, Jeffrey P Greenfield, Theodore H Schwartz
OBJECTIVE The expanded endonasal endoscopic transsphenoidal approach has become increasingly used for craniopharyngioma surgery in the pediatric population, but questions still persist regarding its utility in younger children, in recurrent and irradiated tumors, and in masses primarily located in the suprasellar region. The narrow corridor, incomplete pneumatization, and fear of hypothalamic injury have traditionally relegated this approach to application in older children with mostly cystic craniopharyngiomas centered in the sella...
November 10, 2017: Journal of Neurosurgery. Pediatrics
Lee Moir, Elena G Bochukova, Rebecca Dumbell, Gareth Banks, Rasneer S Bains, Patrick M Nolan, Cheryl Scudamore, Michelle Simon, Kimberly A Watson, Julia Keogh, Elana Henning, Audrey Hendricks, Stephen O'Rahilly, Inês Barroso, Adrienne E Sullivan, David C Bersten, Murray L Whitelaw, Susan Kirsch, Elizabeth Bentley, I Sadaf Farooqi, Roger D Cox
OBJECTIVE: Genetic studies in obese rodents and humans can provide novel insights into the mechanisms involved in energy homeostasis. METHODS: In this study, we genetically mapped the chromosomal region underlying the development of severe obesity in a mouse line identified as part of a dominant N-ethyl-N-nitrosourea (ENU) mutagenesis screen. We characterized the metabolic and behavioral phenotype of obese mutant mice and examined changes in hypothalamic gene expression...
November 2017: Molecular Metabolism
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