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Hypothalamus in weight loss

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https://www.readbyqxmd.com/read/29772029/prolyl-carboxypeptidase-activity-in-the-circulation-and-its-correlation-with-body-weight-and-adipose-tissue-in-lean-and-obese-subjects
#1
Kaat Kehoe, Heidi Noels, Wendy Theelen, Emilie De Hert, Shenguan Xu, An Verrijken, Thierry Arnould, Erik Fransen, Nina Hermans, Anne-Marie Lambeir, Per Venge, Luc Van Gaal, Ingrid De Meester
BACKGROUND: Prolyl carboxypeptidase (PRCP) is involved in the regulation of body weight, likely by hydrolysing alpha-melanocyte-stimulating hormone and apelin in the hypothalamus and in the periphery. A link between PRCP protein concentrations in plasma and metabolic disorders has been reported. In this study, we investigated the distribution of circulating PRCP activity and assessed its relation with body weight and adipose tissue in obese patients and patients who significantly lost weight...
2018: PloS One
https://www.readbyqxmd.com/read/29771336/fto-is-a-transcriptional-repressor-to-auto-regulate-its-own-gene-and-potentially-associated-with-homeostasis-of-body-weight
#2
Shu-Jing Liu, Hui-Ling Tang, Qian He, Ping Lu, Tao Fu, Xu-Ling Xu, Tao Su, Mei-Mei Gao, Shumin Duan, Yan Luo, Yue-Sheng Long
Fat mass and obesity-associated (FTO) protein is a ferrous ion (Fe2+)/2-oxoglutarate (2-OG)-dependent demethylase preferentially catalyzing m6A sites in RNA. The FTO gene is highly expressed in the hypothalamus with fluctuation in response to various nutritional conditions, which is believed to be involved in the control of whole body metabolism. However, the underlying mechanism in response to different nutritional cues remains poorly understood. Here we show that ketogenic diet-derived ketone body β-hydroxybutyrate (BHB) transiently increases FTO expression in both mouse hypothalamus and cultured cells...
May 16, 2018: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/29740148/alterations-of-proteome-mitochondrial-dynamic-and-autophagy-in-the-hypothalamus-during-activity-based-anorexia
#3
Séverine Nobis, Alexis Goichon, Najate Achamrah, Charlène Guérin, Saida Azhar, Philippe Chan, Aline Morin, Christine Bôle-Feysot, Jean Claude do Rego, David Vaudry, Pierre Déchelotte, Liliana Belmonte, Moïse Coëffier
Restrictive anorexia nervosa is associated with reduced eating and severe body weight loss leading to a cachectic state. Hypothalamus plays a major role in the regulation of food intake and energy homeostasis. In the present study, alterations of hypothalamic proteome and particularly of proteins involved in energy and mitochondrial metabolism have been observed in female activity-based anorexia (ABA) mice that exhibited a reduced food intake and a severe weight loss. In the hypothalamus, mitochondrial dynamic was also modified during ABA with an increase of fission without modification of fusion...
May 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29650350/loss-of-dorsomedial-hypothalamic-glp-1-signaling-reduces-bat-thermogenesis-and-increases-adiposity
#4
Shin J Lee, Graciela Sanchez-Watts, Jean-Philippe Krieger, Angelica Pignalosa, Puck N Norell, Alyssa Cortella, Klaus G Pettersen, Dubravka Vrdoljak, Matthew R Hayes, Scott Kanoski, Wolfgang Langhans, Alan G Watts
OBJECTIVE: Glucagon-like peptide-1 (GLP-1) neurons in the hindbrain densely innervate the dorsomedial hypothalamus (DMH), a nucleus strongly implicated in body weight regulation and the sympathetic control of brown adipose tissue (BAT) thermogenesis. Therefore, DMH GLP-1 receptors (GLP-1R) are well placed to regulate energy balance by controlling sympathetic outflow and BAT function. METHODS: We investigate this possibility in adult male rats by using direct administration of GLP-1 (0...
March 21, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29590610/a-transcriptomic-signature-of-the-hypothalamic-response-to-fasting-and-bdnf-deficiency-in-prader-willi-syndrome
#5
Elena G Bochukova, Katherine Lawler, Sophie Croizier, Julia M Keogh, Nisha Patel, Garth Strohbehn, Kitty K Lo, Jack Humphrey, Anita Hokken-Koelega, Layla Damen, Stephany Donze, Sebastien G Bouret, Vincent Plagnol, I Sadaf Farooqi
Transcriptional analysis of brain tissue from people with molecularly defined causes of obesity may highlight disease mechanisms and therapeutic targets. We performed RNA sequencing of hypothalamus from individuals with Prader-Willi syndrome (PWS), a genetic obesity syndrome characterized by severe hyperphagia. We found that upregulated genes overlap with the transcriptome of mouse Agrp neurons that signal hunger, while downregulated genes overlap with the expression profile of Pomc neurons activated by feeding...
March 27, 2018: Cell Reports
https://www.readbyqxmd.com/read/29575771/the-habenula-as-a-novel-link-between-the-homeostatic-and-hedonic-pathways-in-cancer-associated-weight-loss-a-pilot-study
#6
Maria Maldonado, David L Molfese, Humsini Viswanath, Kaylah Curtis, Ashley Jones, Teresa G Hayes, Marco Marcelli, Sanjay Mediwala, Philip Baldwin, Jose M Garcia, Ramiro Salas
BACKGROUND: Little is known about the brain mechanisms underlying cancer-associated weight loss (C-WL) in humans despite this condition negatively affecting their quality of life and survival. We tested the hypothesis that patients with C-WL have abnormal connectivity in homeostatic and hedonic brain pathways together with altered brain activity during food reward. METHODS: In 12 patients with cancer and 12 healthy controls, resting-state functional connectivity (RSFC, resting brain activity observed through changes in blood flow in the brain which creates a blood oxygen level-dependent signal that can be measured using functional magnetic resonance imaging) was used to compare three brain regions hypothesized to play a role in C-WL: the hypothalamus (homeostatic), the nucleus accumbens (hedonic), and the habenula (an important regulator of reward)...
March 25, 2018: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/29538761/an-open-label-clinical-trial-of-hypothalamic-deep-brain-stimulation-for-human-morbid-obesity-bless-study-protocol
#7
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
https://www.readbyqxmd.com/read/29508270/sleeve-gastrectomy-reversed-obesity-induced-hypogonadism-in-a-rat-model-by-regulating-inflammatory-responses-in-the-hypothalamus-and-testis
#8
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
https://www.readbyqxmd.com/read/29475604/deep-brain-stimulation-as-a-therapeutic-option-for-obesity-a-critical-review
#9
REVIEW
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
https://www.readbyqxmd.com/read/29453460/development-and-initial-characterization-of-a-novel-ghrelin-receptor-crispr-cas9-knockout-wistar-rat-model
#10
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
https://www.readbyqxmd.com/read/29440124/sorcs1-and-sorcs3-control-energy-balance-and-orexigenic-peptide-production
#11
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...
April 2018: EMBO Reports
https://www.readbyqxmd.com/read/29403354/hypothalamic-alterations-in-neurodegenerative-diseases-and-their-relation-to-abnormal-energy-metabolism
#12
REVIEW
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
https://www.readbyqxmd.com/read/29398616/hypothalamic-mir-219-regulates-individual-metabolic-differences-in-response-to-diet-induced-weight-cycling
#13
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...
March 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29379898/anti-ma-1-and-anti-ma-2-antibodies-in-isolated-fatal-hypothalamitis
#14
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
https://www.readbyqxmd.com/read/29367426/leptin-replacement-reestablishes-brain-insulin-action-in-the-hypothalamus-in-congenital-leptin-deficiency
#15
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...
April 2018: Diabetes Care
https://www.readbyqxmd.com/read/29261404/hypothalamic-grp78-a-new-target-against-obesity
#16
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/29241183/leptin-suppresses-glutamate-induced-apoptosis-through-regulation-of-erk1-2-signaling-pathways-in-rat-primary-astrocytes
#17
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
https://www.readbyqxmd.com/read/29233861/restoration-of-metabolic-inflammation-related-ghrelin-resistance-by-weight-loss
#18
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
https://www.readbyqxmd.com/read/29217450/cadm2-regulates-body-weight-and-energy-homeostasis-in-mice
#19
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
https://www.readbyqxmd.com/read/29186532/loss-of-offspring-peg3-reduces-neonatal-ultrasonic-vocalizations-and-increases-maternal-anxiety-in-wild-type-mothers
#20
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
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