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Hypothalamus in weight loss

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https://www.readbyqxmd.com/read/28326295/role-of-the-cytokine-like-hormone-leptin-in-muscle-bone-crosstalk-with-aging
#1
REVIEW
Mark W Hamrick
The cytokine-like hormone leptin is a classic adipokine that is secreted by adipocytes, increases with weight gain, and decreases with weight loss. Additional studies have, however, shown that leptin is also produced by skeletal muscle, and leptin receptors are abundant in both skeletal muscle and bone-derived mesenchymal (stromal) stem cells. These findings suggest that leptin may play an important role in muscle-bone crosstalk. Leptin treatment in vitro increases the expression of myogenic genes in primary myoblasts, and leptin treatment in vivo increases the expression of microRNAs involved in myogenesis...
February 2017: Journal of Bone Metabolism
https://www.readbyqxmd.com/read/28324017/a-novel-selective-bombesin-receptor-subtype-3-agonist-promotes-weight-loss-in-male-diet-induced-obese-rats-with-circadian-rhythm-change
#2
Yasunori Nio, Natsu Hotta, Minoru Maruyama, Kenichi Hamagami, Toshimi Nagi, Masaaki Funata, Junichi Sakamoto, Masanori Nakakariya, Nobuyuki Amano, Tomohiro Okawa, Yasuyoshi Arikawa, Shinobu Sasaki, Shoki Okuda, Shizuo Kasai, Yugo Habata, Yasutaka Nagisa
Bombesin receptor subtype 3 (BRS-3) is an orphan G-protein-coupled receptor. Based on the obese phenotype of male BRS-3-deficient mice, BRS-3 has been considered an attractive target for obesity treatment. Here, we developed a novel selective BRS-3 agonist (Compound-A) and evaluated its anti-obesity effects. Compound-A showed anorectic effects and enhanced energy expenditure in diet-induced obese (DIO)-F344 rats. Moreover, repeated oral administration of Compound-A for 7 days resulted in a significant body weight reduction in DIO-F344 rats...
March 16, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323920/perinatal-exposure-to-low-dose-bisphenol-a-bpa-disrupts-the-structural-and-functional-development-of-the-hypothalamic-feeding-circuitry
#3
Harry MacKay, Zachary R Patterson, Alfonso Abizaid
Bisphenol-A (BPA) is a component of polycarbonate and other plastics to which humans are regularly exposed at low levels. BPA is characterized as an endocrine disruptor due to observations of its estrogenic activity in various experimental models. We have previously shown evidence of disrupted hypothalamic feeding circuitry and leptin sensitivity in adult BPA-exposed animals subject to a high-fat diet, but because these animals were already exhibiting a diet-induced obese phenotype, we could not rule out the possibility that these observations were simply consequences of the obesity, not a pre-existing phenotype produced by BPA exposure...
February 7, 2017: Endocrinology
https://www.readbyqxmd.com/read/28301916/a-role-of-central-nell2-in-the-regulation-of-feeding-behavior-in-rats
#4
Jin Kwon Jeong, Jae Geun Kim, Han Rae Kim, Tae Hwan Lee, Jeong Woo Park, Byung Ju Lee
A brain-enriched secreting signal peptide, NELL2, has been suggested to play multiple roles in the development, survival, and activity of neurons in mammal. We investigated here a possible involvement of central NELL2 in regulating feeding behavior and metabolism. In situ hybridization and an immunohistochemical approach were used to determine expression of NELL2 as well as its colocalization with proopiomelanocortin (POMC) and neuropeptide Y (NPY) in the rat hypothalamus. To investigate the effect of NELL2 on feeding behavior, 2 nmole of antisense NELL2 oligodeoxynucleotide was administered into the lateral ventricle of adult male rat brains for 6 consecutive days, and changes in daily body weight, food, and water intake were monitored...
March 15, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28291683/a-pegylated-analog-of-short-length-neuromedin-u-with-potent-anorectic-and-anti-obesity-effects
#5
Hiroshi Inooka, Kotaro Sakamoto, Tokuyuki Shinohara, Yasushi Masuda, Michiko Terada, Satoshi Kumano, Kotaro Yokoyama, Jiro Noguchi, Naoki Nishizawa, Hidenori Kamiguchi, Hisashi Fujita, Taiji Asami, Shiro Takekawa, Tetsuya Ohtaki
Neuromedin U (NMU) is a neuropeptide known to regulate food intake and energy homeostasis that is widely distributed in the gastrointestinal tract, hypothalamus, and pituitary. A short form of NMU, porcine NMU-8 has potent agonist activity for the receptors NMUR1 and NMUR2; however, its short half-life precludes its effective use in vivo. To address this limitation, we designed and synthesized NMU-8 analogs modified by polyethylene glycol (PEG) with a molecular weight of 30kDa (PEG30k) via a variety of linkers (i...
February 21, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28261955/a-randomized-placebo-controlled-trial-of-beloranib-for-the-treatment-of-hypothalamic-injury-associated-obesity
#6
Ashley Shoemaker, Joseph Proietto, M Jennifer Abuzzahab, Tania Markovic, Jaret Malloy, Dennis D Kim
AIMS: Hypothalamic injury-associated obesity (HIAO) results from damage to the hypothalamus that often occurs with surgical removal/radiation therapy of tumors in the hypothalamic region, such as craniopharyngioma. There is currently no rigorously studied pharmaceutical treatment for the intractable weight gain and cardiometabolic consequences that occur in patients with HIAO. We aimed to assess efficacy, safety, and tolerability of beloranib treatment for 4 to 8 weeks in patients with HIAO...
March 6, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28242830/suppressed-sympathetic-outflow-to-skeletal-muscle-muscle-thermogenesis-and-activity-energy-expenditure-with-calorie-restriction
#7
Tariq I Almundarij, Chaitanya K Gavini, Colleen M Novak
During weight loss, adaptive thermogenesis occurs where energy expenditure (EE) is suppressed beyond that predicted for the smaller body size. Here, we investigated the contributions of resting and nonresting EE to the reduced total EE seen after 3 weeks of 50% calorie restriction (CR) in rats, focusing on activity-associated EE, muscle thermogenesis, and sympathetic outflow. Prolonged food restriction resulted in a 42% reduction in daily EE, through a 40% decrease in resting EE, and a 48% decline in nonresting EE These decreases in EE were significant even when the reductions in body weight and lean mass were taken into account...
February 2017: Physiological Reports
https://www.readbyqxmd.com/read/28192820/estrogen-maintains-skeletal-muscle-in-septic-rats-associated-with-altering-hypothalamic-inflammation-and-neuropeptides
#8
Chenyan Zhao, Jun Li, Minhua Cheng, Jialing Shi, Juanhong Shen, Tao Gao, Fengchan Xi, Wenkui Yu
Muscle wasting is one of the main contributors to the worse outcomes in sepsis. Whether estrogen could alleviate muscle wasting induced by sepsis remains unclear. This study was designed to test the effect of estrogen on muscle wasting and its relationship with central alteration in sepsis. Thirty Sprague-Dawley rats were divided into 3 groups: control group, sepsis group, and estrogen treated sepsis group. Animals were intraperitoneally injected with lipopolysaccharide (10 mg/kg) or saline, followed by subcutaneous injection of 17β-estradiol (1 mg/kg) or saline...
February 13, 2017: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/28093506/the-tyrosine-kinase-receptor-tyro3-enhances-lifespan-and-neuropeptide-y-npy-neuron-survival-in-the-mouse-anorexia-anx-mutation
#9
Dennis Y Kim, Joanna Yu, Ryan K Mui, Rieko Niibori, Hamza Bin Taufique, Rukhsana Aslam, John W Semple, Sabine P Cordes
Severe appetite and weight loss define the eating disorder anorexia nervosa, and can also accompany the progression of some neurodegenerative disorders, such as amyotrophic lateral scelerosis (ALS). While acute loss of hypothalamic neurons that produce appetite-stimulating neuropeptide Y (Npy) and agouti related peptide (AgRP) in adult mice or in mice homozygous for the anorexia (anx) mutation causes aphagia, our understanding of the factors that help maintain appetite regulatory circuitry is limited. Here we identify a mutation that converts an arginine to a tryptophan (R7W) in the Tyrosine receptor kinase 3 (Tyro3) gene, which resides within the anx critical interval, as contributing to the severity of anx phenotypes...
January 12, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28057699/glucagon-like-peptide-1-and-its-analogues-act-in-the-dorsal-raphe-and-modulate-central-serotonin-to-reduce-appetite-and-body-weight
#10
Rozita H Anderberg, Jennifer E Richard, Kim Eerola, Lorena Lopez Ferreras, Elin Banke Nordbeck, Caroline Hansson, Hans Nissbrandt, Filip Berqquist, Fiona M Gribble, Frank Reimann, Ingrid Wernstedt-Asterholm, Christophe Lamy, Karolina P Skibicka
Glucagon-like peptide-1 (GLP-1) and serotonin play critical roles in energy balance regulation. Both systems are exploited clinically as anti-obesity strategies. Surprisingly whether they interact in order to regulate energy balance is poorly understood. Here we investigated mechanisms by which GLP-1 and serotonin interact at the level of the CNS. Serotonin depletion impaired the ability of exendin-4, a clinically utilized GLP-1 analogue, to reduce body weight in rats, suggesting serotonin is a critical mediator of the energy balance impact of GLP-1R activation...
January 5, 2017: Diabetes
https://www.readbyqxmd.com/read/28053040/disruption-of-glucagon-like-peptide-1-signaling-in-sim1-neurons-reduces-physiological-and-behavioral-reactivity-to-acute-and-chronic-stress
#11
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, a transcription factor abundantly expressed in the paraventricular nucleus (PVN) of the hypothalamus. Mice with single-minded 1-mediated Glp1r knockdown had reduced hypothalamic-pituitary-adrenal axis responses to both acute and chronic stress and were protected against weight loss associated with chronic stress...
January 4, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27913573/thyroid-hormones-induce-browning-of-white-fat
#12
Noelia Martínez-Sánchez, José M Moreno-Navarrete, Cristina Contreras, Eva Rial-Pensado, Johan Fernø, Rubén Nogueiras, Carlos Diéguez, José-Manuel Fernández-Real, Miguel López
The canonical view about the effect of thyroid hormones (THs) on thermogenesis assumes that the hypothalamus acts merely as a modulator of the sympathetic outflow on brown adipose tissue (BAT). Recent data have challenged that vision by demonstrating that THs act on the ventromedial nucleus of the hypothalamus (VMH) to inhibit AMP-activated protein kinase (AMPK), which regulates the thermogenic program in BAT, leading to increased thermogenesis and weight loss. Current data have shown that in addition to activation of brown fat, the browning of white adipose tissue (WAT) might also be an important thermogenic mechanism...
February 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/27911148/effects-of-chronic-estrogen-administration-in-the-ventromedial-nucleus-of-the-hypothalamus-vmh-on-fat-and-bone-metabolism-in-ovariectomized-rats
#13
Z Zhang, J Liu, A G Veldhuis-Vlug, Y Su, E Foppen, B C J van der Eerden, M Koedam, N Bravenboer, A Kalsbeek, A Boelen, E Fliers, P H Bisschop
Estrogen deficiency after ovariectomy (OVX) results in increased adiposity and bone loss, which can be prevented by systemic 17-β estradiol (E2) replacement. Studies in transgenic mice suggested that in addition to direct actions of estrogen in peripheral tissues, also estrogen signaling in the hypothalamus regulates fat distribution and bone metabolism. We hypothesized that the protective effect of systemic E2 on fat and bone metabolism in the OVX model is partly mediated through the ventromedial nucleus of the hypothalamus (VMH)...
December 2016: Endocrinology
https://www.readbyqxmd.com/read/27908915/the-hypothalamic-glucagon-like-peptide-1-receptor-is-sufficient-but-not-necessary-for-the-regulation-of-energy-balance-and-glucose-homeostasis-in-mice
#14
Melissa A Burmeister, Jennifer E Ayala, Hannah Smouse, Adriana Landivar-Rocha, Jacob D Brown, Daniel J Drucker, Doris A Stoffers, Darleen A Sandoval, Randy J Seeley, Julio E Ayala
Pharmacological activation of the hypothalamic glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) promotes weight loss and improves glucose tolerance. This demonstrates that the hypothalamic GLP-1R is sufficient but does not show whether it is necessary for the effects of exogenous GLP-1R agonists (GLP-1RA) or endogenous GLP-1 on these parameters. To address this, we crossed mice harboring floxed Glp1r alleles to mice expressing Nkx2.1-Cre to knock down Glp1r expression throughout the hypothalamus (GLP-1RKD(ΔNkx2...
February 2017: Diabetes
https://www.readbyqxmd.com/read/27899482/transient-receptor-potential-canonical-3-trpc3-channels-are-required-for-hypothalamic-glucose-detection-and-energy-homeostasis
#15
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
https://www.readbyqxmd.com/read/27886210/physical-activity-energy-expenditure-and-defense-of-body-weight-in-melanocortin-4-receptor-deficient-male-rats
#16
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
https://www.readbyqxmd.com/read/27876617/canagliflozin-a-sodium-glucose-cotransporter-2-inhibitor-attenuates-obesity-induced-inflammation-in-the-nodose-ganglion-hypothalamus-and-skeletal-muscle-of-mice
#17
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...
January 5, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27822713/dexamethasone-alters-the-appetite-regulation-via-induction-of-hypothalamic-insulin-resistance-in-rat-brain
#18
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
https://www.readbyqxmd.com/read/27819311/global-changes-in-lipid-profiles-of-mouse-cortex-hippocampus-and-hypothalamus-upon-p53-knockout
#19
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
https://www.readbyqxmd.com/read/27810935/disruption-of-glucagon-like-peptide-1-signaling-in-sim1-neurons-reduces-physiological-and-behavioral-reactivity-to-acute-and-chronic-stress
#20
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
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