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Hypothalamic Obesity

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https://www.readbyqxmd.com/read/29129795/orexin-a-hypocretin-1-immunoreactivity-in-the-lateral-hypothalamus-is-reduced-in-genetically-obese-but-not-in-diet-induced-obese-mice
#1
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 neurones 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...
November 9, 2017: Neuroscience
https://www.readbyqxmd.com/read/29129597/cocaine-and-desipramine-elicit-distinct-striatal-noradrenergic-and-behavioral-responses-in-selectively-bred-obesity-resistant-and-obesity-prone-rats
#2
Peter J Vollbrecht, Kathryn M Nesbitt, Omar S Mabrouk, Aaron M Chadderdon, Emily M Jutkiewicz, Robert T Kennedy, Carrie R Ferrario
Previous studies have demonstrated a role for norepinephrine (NE) in energy regulation and feeding, and basal differences have been observed in hypothalamic NE systems in obesity-prone vs. obesity-resistant rats. Differences in the function of brain reward circuits, including in the nucleus accumbens (NAc), have been shown in obesity-prone vs. obesity-resistant populations, leading many researchers to explore the role of striatal dopamine in obesity. However, alterations in NE transmission also affect NAc mediated behaviors...
November 9, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/29121420/obesity-during-pregnancy-in-the-mouse-alters-the-netrin-1-responsiveness-of-fetal-arcuate-nucleus-npy-neurons
#3
Tessa R Sanders, Kelly A Glendining, Christine L Jasoni
When individuals undergo gestation in an obese dam, they are at increased risk for impairments in the brain's ability to regulate body weight. In rodents, gestation in an obese dam leads to a number of changes to the development of the hypothalamic neurons that regulate body weight, including reduced neuronal connectivity at birth. Here, we sought to gain a clearer picture of how this neural circuitry develops normally, and to explore the mechanism underpinning the deficiency in connectivity seen in fetuses developing in obese dams...
November 9, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/29121414/stress-induced-suppression-of-neuropeptide-y-induced-hunger-in-anorexic-chicks-involves-corticotropin-releasing-factor-signaling-and-the-paraventricular-nucleus-of-the-hypothalamus
#4
Jinxin Wang, Jiaqing Yi, Paul B Siegel, Mark A Cline, Elizabeth R Gilbert
The Virginia lines of chickens have been selected for low (LWS) or high (HWS) juvenile body weight and have different severities of anorexia and obesity, respectively. The LWS that are exposed to stressors at hatch are refractory to neuropeptide Y (NPY)-induced food intake and the objective was to elucidate the underlying mechanisms. Chicks were exposed to a stressor (-20°C for 6 minutes, and 22°C and delayed access to food for 24 hours) after hatch and hypothalamic nuclei, including the lateral hypothalamus (LH), paraventricular nucleus (PVN), ventromedial hypothalamus (VMH), and arcuate nucleus (ARC), were collected 5 days later...
November 9, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/29111188/food-intake-regulation-by-leptin-mechanisms-mediating-gluconeogenesis-and-energy-expenditure
#5
REVIEW
Zulfia Hussain, Junaid Ali Khan
Regulation of blood glucose levels and body fat is critical for survival. Leptin circulates freely in blood and controls body weight and food intake mainly through hypothalamic receptors and regulates glucose metabolism in the liver both directly through leptin receptors and indirectly via the hypothalamic receptors of central nervous system. Leptin affects food intake regulation and eventually glucose metabolism, lipometabolism, endocrine and immune functions, reproductive function, adipose tissue metabolism and energy expenditure...
October 2017: Asian Pacific Journal of Tropical Medicine
https://www.readbyqxmd.com/read/29107289/disruption-of-the-homeodomain-transcription-factor-orthopedia-homeobox-otp-is-associated-with-obesity-and-anxiety
#6
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
https://www.readbyqxmd.com/read/29102876/maternal-high-fat-diet-induces-sex-specific-endocannabinoid-system-changes-in-newborn-rats-and-programs-adiposity-energy-expenditure-and-food-preference-in-adulthood
#7
Camilla P Dias-Rocha, Mariana M Almeida, Erika M Santana, Julia C B Costa, Juliana G Franco, Carmen C Pazos-Moura, Isis H Trevenzoli
Early life inadequate nutrition triggers developmental adaptations and adult chronic disease. Maternal high-fat (HF) diet promotes visceral obesity and hypothalamic leptin resistance in male rat offspring at weaning and adulthood. Obesity is related to over active endocannabinoid system (ECS). The ECS consists mainly of endogenous ligands, cannabinoid receptors (CB1 and CB2), and the enzymes fatty acid anandamide hydrolase (FAAH) and monoacylglycerol lipase (MAGL). We hypothesized that perinatal maternal HF diet would regulate offspring ECS in hypothalamus and brown adipose tissue (BAT) at birth, prior to visceral obesity development, and program food preference and energy expenditure of adult offspring...
October 5, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29099963/activity-of-the-hypothalamic-melanocortin-system-decreases-in-middle-aged-and-increases-in-old-rats
#8
Nóra Füredi, Alexandra Mikó, Balázs Gaszner, Diána Feller, Ildikó Rostás, Judit Tenk, Margit Solymár, Márta Balaskó, Erika Pétervári
Appearance of middle-aged obesity and aging anorexia both in humans and rodents suggests a role for regulatory alterations. Hypothalamic melanocortin agonist, alpha-melanocyte-stimulating hormone (alpha-MSH) produced in the arcuate nucleus (ARC) reduces body weight via inducing hypermetabolism and anorexia mainly through melanocortin 4 receptors (MC4R) in the paraventricular nucleus (PVN). Orexigenic ARC-derived agouti-related protein (AgRP) is an inverse agonist on MC4R in the PVN. Previously we demonstrated that characteristic age-related shifts in the catabolic effects of alpha-MSH may contribute both to middle-aged obesity and aging anorexia...
November 1, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/29097992/circadian-and-metabolic-effects-of-light-implications-in-weight-homeostasis-and-health
#9
REVIEW
Santiago A Plano, Leandro P Casiraghi, Paula García Moro, Natalia Paladino, Diego A Golombek, Juan J Chiesa
Daily interactions between the hypothalamic circadian clock at the suprachiasmatic nucleus (SCN) and peripheral circadian oscillators regulate physiology and metabolism to set temporal variations in homeostatic regulation. Phase coherence of these circadian oscillators is achieved by the entrainment of the SCN to the environmental 24-h light:dark (LD) cycle, coupled through downstream neural, neuroendocrine, and autonomic outputs. The SCN coordinate activity and feeding rhythms, thus setting the timing of food intake, energy expenditure, thermogenesis, and active and basal metabolism...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/29090684/neuroactive-steroids-and-affective-symptoms-in-women-across-the-weight-spectrum
#10
Laura E Dichtel, Elizabeth A Lawson, Melanie Schorr, Erinne Meenaghan, Margaret Lederfine Paskal, Kamryn T Eddy, Graziano Pinna, Marianela Nelson, Ann M Rasmusson, Anne Klibanski, Karen K Miller
3α-5α-Tetrahydroprogesterone, a progesterone metabolite also known as allopregnanolone, and 5α-androstane-3α,17β-diol, a testosterone metabolite also known as 3α-androstanediol, are neuroactive steroids and positive GABAA receptor allosteric modulators. Both anorexia nervosa (AN) and obesity are complicated by affective co-morbidities and hypothalamic-pituitary-gonadal dysregulation. However, it is not known whether neuroactive steroid levels are abnormal at the extremes of the weight spectrum. We hypothesized that serum allopregnanolone and 3α-androstanediol levels would be decreased in AN compared to healthy controls (HC) and negatively associated with affective symptoms throughout the weight spectrum, independent of body mass index (BMI)...
November 1, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29089613/glp-1-and-igf-i-levels-are-elevated-in-late-infancy-in-low-birthweight-infants-independently-of-glp-1-receptor-polymorphisms-and-neonatal-nutrition
#11
M Díaz, C García-Beltran, A López-Bermejo, F de Zegher, L Ibáñez
Low birth weight followed by rapid postnatal weight gain is associated with increased risks for obesity and diabetes in adulthood. Modulation of glucagon-like-peptide 1 (GLP-1) secretion by (epi)genetic mechanisms or nutrition may influence in part this risk. Formula fed infants born small-for-gestational-age (SGA) have higher circulating GLP-1 at age 4 months than breastfed SGA or appropriate-for-gestational-age (AGA) infants. Here, we assessed GLP-1 concentrations in healthy AGA (n=149) and SGA (n=107) subjects at age 12 months, and their association with endocrine-metabolic and body composition parameters and GLP-1 receptor (GLP-1R) rs6923761 and rs3765467 polymorphisms...
November 1, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29089444/pre-synaptic-regulation-of-leptin-in-a-defined-lateral-hypothalamus-ventral-tegmental-area-neurocircuitry-depends-on-energy-state
#12
Jing-Jing Liu, Nicholas T Bello, Zhiping P Pang
Synaptic transmission controls information flow in the brain and expression of all brain-related behaviors, including food intake. Leptin, an adipocyte-derived hormone, acts on neurons located in the lateral hypothalamus (LHA) to maintain energy homeostasis and regulate food intake behavior. The specific synaptic mechanisms, cell types and neural projections mediating this effect remain unclear. In male mice, using pathway-specific retrograde tracing, whole cell patch clamp recordings and posthoc cell type identification, we found that leptin reduces excitatory synaptic strength onto both melanin-concentrating hormone (MCH) and orexin-expressing neurons projecting from the LHA to the ventral tegmental area (VTA), which may affect dopamine signaling and motivation for feeding...
October 31, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29075199/brain-ceramide-metabolism-in-the-control-of-energy-balance
#13
REVIEW
Céline Cruciani-Guglielmacci, Miguel López, Mélanie Campana, Hervé le Stunff
The regulation of energy balance by the central nervous system (CNS) is a key actor of energy homeostasis in mammals, and deregulations of the fine mechanisms of nutrient sensing in the brain could lead to several metabolic diseases such as obesity and type 2 diabetes (T2D). Indeed, while neuronal activity primarily relies on glucose (lactate, pyruvate), the brain expresses at high level enzymes responsible for the transport, utilization and storage of lipids. It has been demonstrated that discrete neuronal networks in the hypothalamus have the ability to detect variation of circulating long chain fatty acids (FA) to regulate food intake and peripheral glucose metabolism...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29068243/evidence-for-disruption-of-normal-circadian-cortisol-rhythm-in-women-with-obesity
#14
Zain A Al-Safi, Alex Polotsky, Justin Chosich, Lauren Roth, Amanda A Allshouse, Andrew P Bradford, Nanette Santoro
Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis may play a role in the pathogenesis of comorbidities encountered in obesity, including the relative hypogonadotropic hypogonadism that we and others have observed. We sought to examine serum cortisol profiles throughout the day and evening in a sample of normal weight women and women with obesity. In this cross-sectional study, regularly cycling obese (n = 12) and normal weight (n = 10) women were recruited. Mean serum cortisol was measured by frequent blood sampling for 16 h (8am-midnight) in the luteal phase of the menstrual cycle...
October 25, 2017: Gynecological Endocrinology
https://www.readbyqxmd.com/read/29064566/generation-and-characterization-of-functional-human-hypothalamic-neurons
#15
Peter Kirwan, Magdalena Jura, Florian T Merkle
Neurons in the hypothalamus orchestrate homeostatic physiological processes and behaviors essential for life. Defects in the function of hypothalamic neurons cause a spectrum of human diseases, including obesity, infertility, growth defects, sleep disorders, social disorders, and stress disorders. These diseases have been studied in animal models such as mice, but the rarity and relative inaccessibility of mouse hypothalamic neurons and species-specific differences between mice and humans highlight the need for human cellular models of hypothalamic diseases...
October 24, 2017: Current Protocols in Neuroscience
https://www.readbyqxmd.com/read/29064475/brain-substrates-of-unhealthy-versus-healthy-food-choices-influence-of-homeostatic-status-and-body-mass-index
#16
I H Harding, Z B Andrews, F Mata, S Orlandea, I Martínez-Zalacaín, C Soriano-Mas, E Stice, A Verdejo-Garcia
BACKGROUND/OBJECTIVES: Unhealthy dietary choices are a major contributor to harmful weight gain and obesity. This study interrogated the brain substrates of unhealthy versus healthy food choices in vivo, and evaluated the influence of hunger state and body mass index (BMI) on brain activation and connectivity. SUBJECTS/METHODS: Thirty adults (BMI: 18-38 kg m(-2)) performed a food-choice task involving preference-based selection between beverage pairs consisting of high-calorie (unhealthy) or low-calorie (healthy) options, concurrent with functional magnetic resonance imaging (fMRI)...
September 25, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29062272/obesity-increases-mitogen-activated-protein-kinase-phosphatase-3-levels-in-the-hypothalamus-of-mice
#17
Bárbara de A Rodrigues, Vitor R Muñoz, Gabriel K Kuga, Rafael C Gaspar, Susana C B R Nakandakari, Barbara M Crisol, José D Botezelli, Luciana S S Pauli, Adelino S R da Silva, Leandro P de Moura, Dennys E Cintra, Eduardo R Ropelle, José R Pauli
Mitogen-activated Protein Kinase Phosphatase 3 (MKP-3) has been involved in the negative regulation of insulin signaling. The absence of MKP-3 is also associated with reduced adiposity, increased energy expenditure and improved insulin sensitivity. The MKP-3 is known as the main Erk1/2 phosphatase and FoxO1 activator, which has repercussions on the gluconeogenesis pathway and hyperglycemia in obese mice. Recently, we showed that MKP-3 overexpression decreases FoxO1 phosphorylation in the hypothalamus of lean mice...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29061165/sustained-endocrine-profiles-of-a-girl-with-wagr-syndrome
#18
Yui Takada, Yasunari Sakai, Yuki Matsushita, Kazuhiro Ohkubo, Yuhki Koga, Satoshi Akamine, Michiko Torio, Yoshito Ishizaki, Masafumi Sanefuji, Hiroyuki Torisu, Chad A Shaw, Masayo Kagami, Toshiro Hara, Shouichi Ohga
BACKGROUND: Wilms tumor, aniridia, genitourinary anomalies and mental retardation (WAGR) syndrome is a rare genetic disorder caused by heterozygous deletions of WT1 and PAX6 at chromosome 11p13. Deletion of BDNF is known eto be associated with hyperphagia and obesity in both humans and animal models; however, neuroendocrine and epigenetic profiles of individuals with WAGR syndrome remain to be determined. CASE PRESENTATION: We report a 5-year-old girl with the typical phenotype of WAGR syndrome...
October 23, 2017: BMC Medical Genetics
https://www.readbyqxmd.com/read/29057457/differential-effects-of-selective-agonists-of-neuromedin-u1-and-2-receptors-in-obese-and-diabetic-mice
#19
Hiroaki Nagai, Tomoko Kaisho, Kotaro Yokoyama, Tomoko Asakawa, Hisashi Fujita, Kouta Matsumiya, Jiro Noguchi, Kazue Tsuchimori, Naoki Nishizawa, Yoko Kanematsu-Yamaki, Katsuko Dote, Hiroshi Inooka, Jun-Ichi Sakamoto, Tetsuya Ohtaki, Taiji Asami, Shiro Takekawa
BACKGROUND AND PURPOSE: Neuromedin U (NMU) may be a novel target for obesity treatment owing to its anorectic and energy expenditure enhancing effects. Although two receptors, NMU1 and NMU2, are both responsible for the NMU-mediated anti-obesity effects, the receptor agonist with the most appropriate profiles for treating obesity and diabetes in terms of efficacy and safety is as yet unknown. Thus, we developed and evaluated novel NMU1/2 receptor-selective agonists. EXPERIMENTAL APPROACH: Efficacy and safety were assessed in mice with diet-induced obesity (DIO) and those with leptin-deficient diabetes (ob/ob) through repeated peripheral administration of selective agonists to NMU1 (NMU-6102) and NMU2 (NMU-2084), along with NMU1/2 non-selective agonists (NMU-0002 and NMU-6014)...
October 22, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29048574/community-crime-exposure-and-risk-for-obesity-in-preschool-children-moderation-by-the-hypothalamic-pituitary-adrenal-axis-response
#20
Maria A Gartstein, Erich Seamon, Stephanie F Thompson, Liliana J Lengua
Objective: Identification of early risk factors related to obesity is critical to preventative public health efforts. In this study, we investigated links between the Hypothalamic-Pituitary-Adrenal (HPA)-axis activity (diurnal cortisol pattern), geospatially operationalized exposure to neighborhood crime, and body mass index (BMI) for a sample of 5-year-old children. Greater community crime exposure and lower HPA-axis activity were hypothesized to contribute to higher BMI, with child HPA-axis moderating the association between crime exposure and BMI...
September 18, 2017: Journal of Pediatric Psychology
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