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Hypothalamic Obesity

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https://www.readbyqxmd.com/read/29352447/long-term-endocrine-effects-and-trends-in-body-mass-index-changes-in-patients-with-childhood-onset-brain-tumors
#1
Go Hun Seo, Jin-Ho Choi, Yoon-Myung Kim, Kyung-Nam Koh, Ho Joon Im, Young Shin Ra, Han-Wook Yoo
As survival rates have improved owing to advances in management strategies for pediatric brain tumors, long-term complications such as endocrine dysfunction, have emerged as a major issue. This study investigated the long-term endocrine effects of childhood-onset brain tumors in a large number of patients. This study included 151 patients with brain tumors diagnosed between January 1995 and December 2016. The following data were retrospectively reviewed: tumor location, tumor histology, endocrine abnormalities, hypothalamic involvement on brain imaging, treatment modalities, and trends in body mass index...
January 19, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29341046/reduced-growth-hormone-secretion-is-associated-with-nonalcoholic-fatty-liver-disease-in-obese-children
#2
Shuang Liang, Zhen Yu, Xiaobo Song, Yu Wang, Meng Li, Jiang Xue
The purpose of the study was to evaluate the relationship between arginine-levodopa-induced growth hormone (GH) secretion and nonalcoholic fatty liver disease (NAFLD) in obese children. This study includes a total of 84 obese and 43 normal weight children. The obese subjects are divided into two groups based on the presence or absence of NAFLD. Clinical examination, anthropometric and laboratory examinations, and liver ultrasonography are assessed for all participants. The obese group had significantly lower peak stimulated GH (p<0...
January 16, 2018: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/29337002/hypothalamic-inflammation-and-malfunctioning-glia-in-the-pathophysiology-of-obesity-and-diabetes-translational-significance
#3
REVIEW
Md Habibur Rahman, Anup Bhusal, Won-Ha Lee, In-Kyu Lee, Kyoungho Suk
Preclinical studies have suggested that chronic inflammation in the brain might be associated with multiple metabolic disorders, including obesity and diabetes. In particular, hypothalamic inflammation interferes with the endocrine system and modulates nutritional homeostasis, leading to metabolic alterations and consequent pathologies. With regard to the mechanisms underlying molecular and cellular pathogenesis, neurons, non-neuronal cells, and the crosstalk between them have gained particular attention. Specifically, malfunctioning glia have recently been implicated as an important component of pathological hypothalamic inflammation...
January 11, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29321684/leptin-and-the-maintenance-of-elevated-body-weight
#4
REVIEW
Warren W Pan, Martin G Myers
Obesity represents the single most important risk factor for early disability and death in developed societies, and the incidence of obesity remains at staggering levels. CNS systems that modulate energy intake and expenditure in response to changes in body energy stores serve to maintain constant body adiposity; the adipocyte-derived hormone leptin and its receptor (LEPR) represent crucial regulators of these systems. As in the case of insulin resistance, a variety of mechanisms (including feedback inhibition, inflammation, gliosis and endoplasmic reticulum stress) have been proposed to interfere with leptin action and impede the systems that control body energy homeostasis to promote or maintain obesity, although the relative importance and contribution of each of these remain unclear...
January 11, 2018: Nature Reviews. Neuroscience
https://www.readbyqxmd.com/read/29321171/sgk1-foxo3-signaling-in-hypothalamic-pomc-neurons-mediates-glucocorticoid-increased-adiposity
#5
Yalan Deng, Yuzhong Xiao, Feixiang Yuan, Yaping Liu, Xiaoxue Jiang, Jiali Deng, Geza Fejes-Toth, Aniko Naray-Fejes-Toth, Shanghai Chen, Yan Chen, Hao Ying, Qiwei Zhai, Yousheng Shu, Feifan Guo
Although central nervous system has been implicated in glucocorticoid-induced fat mass gain, the underlying mechanisms are poorly understood. The aim of our current study was to investigate the possible involvement of hypothalamic serum- and glucocorticoid-regulated kinase 1 (SGK1) in glucocorticoid-increased adiposity. It is well-known that SGK1 expression is induced by acute glucocorticoid treatment, interestingly, we found its expression was decreased in the arcuate nucleus of the hypothalamus, including POMC neurons, following chronic dexamethasone (Dex) treatment...
January 10, 2018: Diabetes
https://www.readbyqxmd.com/read/29314661/the-development-of-hypothalamic-obesity-in-craniopharyngioma-patients-a-risk-factor-analysis-in-a-well-defined-cohort
#6
Laura van Iersel, Ruud W H Meijneke, Antoinette Y N Schouten-van Meeteren, Liesbeth Reneman, Maartje M de Win, A S Paul van Trotsenburg, Peter H Bisschop, Martijn J J Finken, W Peter Vandertop, Wouter R van Furth, Hanneke M van Santen
BACKGROUND: Hypothalamic obesity (HO) is a major concern in patients treated for craniopharyngioma (CP). The influence of degree of resection on development of HO, event-free survival (EFS), and neuroendocrine sequelae is an issue of debate. PROCEDURE: A retrospective cohort consisting of all CP patients treated between 2002 and 2012 in two university hospitals was identified. Multivariable logistic regression was used to study the associations between preoperative BMI, age at diagnosis, tumor volume, performed surgical resection, and presence of HO at follow-up...
January 4, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29314170/pulsatility-of-glucocorticoid-hormones-in-pregnancy-changes-with-gestation-and-obesity
#7
Laura I Stirrat, Jamie J Walker, Ksenia Stryjakowska, Natalie Jones, Natalie Zm Homer, Ruth Andrew, Jane E Norman, Stafford L Lightman, Rebecca M Reynolds
OBJECTIVE: Hypothalamic-pituitary-adrenal-axis (HPA) activity is decreased in obese pregnancy and associates with increased fetal size. Pulsatile release of glucocorticoid hormones regulates their action in target tissues. Glucocorticoids are essential for normal fetal growth but little is known about glucocorticoid pulsatility in pregnancy. We aimed to investigate the ultradian rhythm of glucocorticoid secretion during obese and lean pregnancy and non-pregnancy. DESIGN: Serum cortisol, cortisone, corticosterone and 11-dehydrocorticosterone were measured by LC-MS/MS from samples obtained at 10-minute intervals between 08...
January 5, 2018: Clinical Endocrinology
https://www.readbyqxmd.com/read/29313284/endocrinological-aspects-of-hiv-infection
#8
REVIEW
F S Mirza, P Luthra, L Chirch
PURPOSE: Patients with human immunodeficiency virus (HIV) are living longer with effective antiretroviral therapies and are enjoying near normal life span. Therefore, they are encountering endocrine issues faced by the general population along with those specific to HIV infection. The purpose of this article is to review the common endocrine aspects of HIV infection, and the early detection and management strategies for these complications. METHODS: Recent literature on HIV and endocrine disease was reviewed...
January 8, 2018: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/29311635/subcellular-localization-of-mc4r-with-adcy3-at-neuronal-primary-cilia-underlies-a-common-pathway-for-genetic-predisposition-to-obesity
#9
Jacqueline E Siljee, Yi Wang, Adelaide A Bernard, Baran A Ersoy, Sumei Zhang, Aaron Marley, Mark Von Zastrow, Jeremy F Reiter, Christian Vaisse
Most monogenic cases of obesity in humans have been linked to mutations in genes encoding members of the leptin-melanocortin pathway. Specifically, mutations in MC4R, the melanocortin-4 receptor gene, account for 3-5% of all severe obesity cases in humans 1-3 . Recently, ADCY3 (adenylyl cyclase 3) gene mutations have been implicated in obesity 4,5 . ADCY3 localizes to the primary cilia of neurons 6 , organelles that function as hubs for select signaling pathways. Mutations that disrupt the functions of primary cilia cause ciliopathies, rare recessive pleiotropic diseases in which obesity is a cardinal manifestation 7 ...
January 8, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29311632/bace1-dependent-amyloid-processing-regulates-hypothalamic-leptin-sensitivity-in-obese-mice
#10
Paul J Meakin, Susan M Jalicy, Gemma Montagut, David J P Allsop, Daniella L Cavellini, Stuart W Irvine, Christopher McGinley, Mary K Liddell, Alison D McNeilly, Karolina Parmionova, Yu-Ru Liu, Charlotte L S Bailey, J Kim Dale, Lora K Heisler, Rory J McCrimmon, Michael L J Ashford
Obesity places an enormous medical and economic burden on society. The principal driver appears to be central leptin resistance with hyperleptinemia. Accordingly, a compound that reverses or prevents leptin resistance should promote weight normalisation and improve glucose homeostasis. The protease Bace1 drives beta amyloid (Aβ) production with obesity elevating hypothalamic Bace1 activity and Aβ1-42 production. Pharmacological inhibition of Bace1 reduces body weight, improves glucose homeostasis and lowers plasma leptin in diet-induced obese (DIO) mice...
January 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29305256/from-appetite-setpoint-to-appetition-50years-of-ingestive-behavior-research
#11
Anthony Sclafani
I review the main themes of my 50-year research career in ingestive behavior as a graduate student at the University of Chicago and a professor at the City University of New York. A seminar course with my Ph.D. mentor, S. P. Grossman, sparked my interest in the hypothalamic obesity syndrome. I developed a wire knife to dissect the neuropathways and the functional disorder responsible for the syndrome. An elevated appetite setpoint that permitted the overconsumption of palatable foods appeared central to the hypothalamic syndrome...
January 2, 2018: Physiology & Behavior
https://www.readbyqxmd.com/read/29301606/epac2a-knockout-mice-are-resistant-to-dexamethasone-induced-skeletal-muscle-atrophy-and-short-term-cold-stress
#12
Seung-Eun Song, Su-Kyung Shin, So-Young Park, Il-Seon Hwang, Seung-Soon Im, Jae-Hoon Bae, Myung-Sook Choi, Dae-Kyu Song
Exchange protein directly activated by cAMP (Epac) 2a-knockout (KO) mice exhibit accelerated diet-induced obesity and are resistant to leptin-mediated adipostatic signaling from the hypothalamus to adipose tissue, with sustained food intake. However, the impact of Epac2a deficiency on hypothalamic regulation of sympathetic nervous activity (SNA) has not been elucidated. This study was performed to elucidate the response of Epac2a-KO mice to dexamethasone-induced muscle atrophy and acute cold stress. Compared to age-matched wild-type mice, Epac2a-KO mice showed higher energy expenditures and expression of myogenin and uncoupling protein-1 in skeletal muscle (SM) and brown adipose tissue (BAT), respectively...
January 5, 2018: BMB Reports
https://www.readbyqxmd.com/read/29297124/metabolic-parameters-and-functional-state-of-hypothalamic-signaling-systems-in-ay-a-mice-with-genetic-predisposition-to-obesity-and-the-effect-of-metformin
#13
K V Derkach, I O Zakharova, I V Romanova, I I Zorina, A L Mikhrina, A O Shpakov
The metabolic parameters and functional state of hypothalamic systems in mice with the Yellow mutation in the Agouti locus and with obesity of the melanocortin type and the effect of metformin (MF) treatment (9 days, 200 mg/kg/day) were studied. The MF treatment led to decreased body weight and to normalization of glucose tolerance in mice. In the hypothalamus, MF restored the decreased activity of Akt kinase, the main component of leptin pathway, and normalized the increased expression of subtype 1B serotonin receptor...
November 2017: Doklady. Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29296625/molecular-therapy-of-melanocortin-4-receptor-obesity-by-an-autoregulatory-bdnf-vector
#14
Jason J Siu, Nicholas J Queen, Xianglan Liu, Wei Huang, Travis McMurphy, Lei Cao
Mutations in the melanocortin-4-receptor (MC4R) comprise the most common monogenic form of severe early-onset obesity, and conventional treatments are either ineffective long-term or contraindicated. Immediately downstream of MC4R-in the pathway for regulating energy balance-is brain-derived neurotrophic factor (BDNF). Our previous studies show that adeno-associated virus (AAV)-mediated hypothalamic BDNF gene transfer alleviates obesity and diabetes in both diet-induced and genetic models. To facilitate clinical translation, we developed a built-in autoregulatory system to control therapeutic gene expression mimicking the body's natural feedback systems...
December 15, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/29296618/lateral-hypothalamic-activity-indicates-hunger-and-satiety-states-in-humans
#15
Omid Talakoub, Raquel R Paiva, Matija Milosevic, Marcelo Q Hoexter, Ruth Franco, Eduardo Alho, Jessie Navarro, José F Pereira, Milos R Popovic, Cary Savage, Antonio C Lopes, Pedro Alvarenga, Durval Damiani, Manoel J Teixeira, Euripides C Miguel, Erich T Fonoff, Marcelo C Batistuzzo, Clement Hamani
Lateral hypothalamic area (LHA) local field potentials (LFPs) were recorded in a Prader-Willi patient undergoing deep brain stimulation (DBS) for obesity. During hunger, exposure to food-related cues induced an increase in beta/low-gamma activity. In contrast, recordings during satiety were marked by prominent alpha rhythms. Based on these findings, we have delivered alpha-frequency DBS prior to and during food intake. Despite reporting an early sensation of fullness, the patient continued to crave food. This suggests that the pattern of activity in LHA may indicate hunger/satiety states in humans but attest to the complexity of conducting neuromodulation studies in obesity...
December 2017: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/29290621/a-gut-brain-axis-regulating-glucose-metabolism-mediated-by-bile-acids-and-competitive-fibroblast-growth-factor-actions-at-the-hypothalamus
#16
Shunmei Liu, Genevieve Marcelin, Clemence Blouet, Jae Hoon Jeong, Young-Hwan Jo, Gary J Schwartz, Streamson Chua
OBJECTIVE: Bile acids have been implicated as important regulators of glucose metabolism via activation of FXR and GPBAR1. We have previously shown that FGF19 can modulate glucose handling by suppressing the activity of hypothalamic AGRP/NPY neurons. As bile acids stimulate the release of FGF19/FGF15 into the circulation, we pursued the potential of bile acids to improve glucose tolerance via a gut-brain axis involving FXR and FGF15/FGF19 within enterocytes and FGF receptors on hypothalamic AGRP/NPY neurons...
December 9, 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29286405/live-images-of-glut4-protein-trafficking-in-mouse-primary-hypothalamic-neurons-using-deconvolution-microscopy
#17
Chun Austin Changou, Reni Ajoy, Szu-Yi Chou
Type 2 diabetes mellitus (T2DM) is a global health crisis which is characterized by insulin signaling impairment and chronic inflammation in peripheral tissues. The hypothalamus in the central nervous system (CNS) is the control center for energy and insulin signal response regulation. Chronic inflammation in peripheral tissues and imbalances of certain chemokines (such as CCL5, TNFα, and IL-6) contribute to diabetes and obesity. However, the functional mechanism(s) connecting chemokines and hypothalamic insulin signal regulation still remain unclear...
December 7, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29277394/nitric-oxide-treatment-attenuates-muscle-atrophy-during-hind-limb-suspension-in-mice
#18
Judy E Anderson, Antonia Zhu, Tooru M Mizuno
Debilitating muscle-disuse atrophy in aging or obesity i has huge socioeconomic impact. Since nitric oxide (NO) mediates muscle satellite cell activation and induces hypertrophy with exercise in old mice, we tested whether treatment with the NO donor, isosorbide dinitrate (ISDN), during hind limb suspension would reduce atrophy. Mice were suspended 18 days, with or without daily ISDN (66mg/kg). Muscles were examined for atrophy (weight, fiber diameter); regulatory changes in atrogin-1 (a negative regulator of muscle mass), myostatin (inhibit myogenesis), and satellite cell proliferation; and metabolic responses in myosin heavy chains (MyHCs), liver lipid, and hypothalamic gene expression...
December 19, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29261404/hypothalamic-grp78-a-new-target-against-obesity
#19
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
https://www.readbyqxmd.com/read/29248436/estrogen-signaling-in-the-medial-amygdala-decreases-emotional-stress-responses-and-obesity-in-ovariectomized-rats
#20
Christina M Estrada, Valentina Ghisays, Elizabeth T Nguyen, Jody L Caldwell, Joshua Streicher, Matia B Solomon
Declining estradiol (E2), as occurs during menopause, increases risk for obesity and psychopathology (i.e., depression, anxiety). E2 modulates mood and energy homeostasis via binding to estrogen receptors (ER) in the brain. The often comorbid and bidirectional relationship between mood and metabolic disorders suggests shared hormonal and/or brain networks. The medial amygdala (MeA) is abundant in ERs and regulates mood, endocrine, and metabolic stress responses; therefore we tested the hypothesis that E2 in the MeA mitigates emotional and metabolic dysfunction in a rodent model of surgical menopause...
December 14, 2017: Hormones and Behavior
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