Article
Biochemistry & Molecular Biology
Iris Stoltenborg, Fiona Peris-Sampedro, Erik Schele, Marie V. Le May, Roger A. H. Adan, Suzanne L. Dickson
Summary: The availability of Cre-based mouse lines has helped identify the neural circuitry driving hormone effects. As an alternative method, TRAP2 mice provide genetic access to hormone-activated populations. By utilizing TRAP2 mice, researchers visualized and stimulated ghrelin-activated cells, discovering their significant role in inducing an orexigenic response and impacting food choice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Rafael Appel Flores, Renata Steinbach, Joao A. B. Pedroso, Martin Metzger, Jose Donato, Marta Aparecida Paschoalini
Summary: The study aimed to evaluate the effects of pharmacological manipulation of alpha-adrenergic agonists in the dorsal raphe nucleus on food intake in satiated rats. Administration of noradrenaline, adrenaline, and clonidine into the DR increased food intake and decreased latency to start consumption in satiated rats. The data suggest that the hyperphagia induced by noradrenaline or adrenaline treatment depends on alpha-2 adrenoceptors activation and that clonidine injections impact neuronal activity in the arcuate nucleus.
Article
Nutrition & Dietetics
Yermek Rakhat, Kentaro Kaneko, Lei Wang, Wanxin Han, Yutaka Seino, Daisuke Yabe, Toshihiko Yada
Summary: d-allulose can suppress hunger-associated feeding and inhibit hunger-promoting neurons in the hypothalamic arcuate nucleus.
Article
Biochemistry & Molecular Biology
Roldan Medina de Guia, Anna S. Hassing, Tao Ma, Kaja Plucinska, Birgitte Holst, Zach Gerhart-Hines, Brice Emanuelli, Jonas T. Treebak
Summary: Deletion of Nampt in AgRP neurons causes progressive neurodegeneration and impairs responses to fasting and ghrelin in a context-dependent manner.
Article
Endocrinology & Metabolism
Fiona Peris-Sampedro, Iris Stoltenborg, Marie V. Le May, Jeffrey M. Zigman, Roger A. H. Adan, Suzanne L. Dickson
Summary: This study evaluated the physical and metabolic phenotypes of heterozygous and homozygous Ghsr-IRES-Cre mice, finding that heterozygotes retain responsiveness to ghrelin, while homozygotes exhibit growth retardation.
MOLECULAR METABOLISM
(2021)
Review
Behavioral Sciences
Anil Joshi, Marion Schott, Susanne Eva la Fleur, Michel Barrot
Summary: Food intake is a necessary behavior for all animals, but excessive consumption of fat and sugar can lead to obesity. This review provides insights into the impact of food intake on the striatal complex and the modulation of palatable food intake by different neurochemical systems.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2022)
Article
Endocrinology & Metabolism
Guangpin Chu, Hualing Peng, Nana Yu, Yuejin Zhang, Xueling Lin, Yisheng Lu
Summary: The overexpression of LEAP2 in the hypothalamic arcuate nucleus reduces food intake and body weight, improves metabolic disorders, and increases the expression of POMC. Central delivery of LEAP2 leads to appetite suppression and weight reduction.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jia Sun, Xinyuan Wang, Rui Sun, Xiaoao Xiao, Yu Wang, Yu Peng, Yuanqing Gao
Summary: The hypothalamus plays a critical role in metabolism and energy balance, and microglia, the immune cells in the brain, have been shown to influence neurodevelopment. This study investigated the role of microglia in the postnatal development of hypothalamic neural circuits and found that their depletion during a critical period increased the number and density of AgRP neurons, leading to increased neonatal feeding behavior. Mechanistically, microglia can engulf perineuronal net components, and their absence resulted in increased perineuronal net formation and enhanced leptin sensitivity in the hypothalamus.
MOLECULAR PSYCHIATRY
(2023)
Editorial Material
Biochemistry & Molecular Biology
Monica Imbernon, Benedicte Dehouck, Vincent Prevot
Summary: The suprachiasmatic nucleus plays a crucial role in synchronizing physiology with the individual's environment, while tanycytes regulate the circadian changes in brain glucose entry and glycemia under the tempo set by the SCN.
Article
Medicine, Research & Experimental
Alice Adriaenssens, Johannes Broichhagen, Anne de Bray, Julia Ast, Annie Hasib, Ben Jones, Alejandra Tomas, Natalie Figueredo Burgos, Orla Woodward, Jo Lewis, Elisabeth O'Flaherty, Kimberley El, Canqi Cui, Norio Harada, Nobuya Inagaki, Jonathan Campbell, Daniel Brierley, David J. Hodson, Ricardo Samms, Fiona Gribble, Frank Reimann
Summary: The signaling pathways of the central glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) in the brain are not fully understood, and its role in GIP-based therapeutics for weight loss is critical. This study found that Gipr neurons in the hypothalamus and dorsal vagal complex (DVC) play a role in the control of energy balance, but they have different connectivity, transcriptomic profiles, and appetite-controlling mechanisms. The study also showed that GIPR agonists have restricted access to the central nervous system, primarily targeting circumventricular organs. These findings highlight the heterogeneity of the central GIPR signaling axis and suggest the need to consider multiple regulatory pathways in studying the effects of GIP pharmacology on feeding behavior.
Article
Behavioral Sciences
Jessica Frayre, Priscila Frayre, Ida Wong, Anusha Mithani, Stephanie Bishop, Chelsy Mani, Karen Ponce-Rubio, Ruvaid Virk, Michael J. Morris, Elisa S. Na
Summary: Obesity is a complex disease influenced by various factors including genetics, environment, and hormonal abnormalities. Research suggests that exposure to high fat diet can decrease MeCP2 protein expression in the hypothalamus, particularly affecting different regions in male and female mice. This indicates a developmentally sensitive period where MeCP2 expression is impacted by high fat diet exposure in a sexually dimorphic manner.
BEHAVIOURAL BRAIN RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Zhengxiang Huang, Xuehan Lu, Lili Huang, Chunhong Zhang, Johannes D. Veldhuis, Michael A. Cowley, Chen Chen
Summary: Stimulation of endogenous GH secretion by hexarelin can improve fat metabolism in obese mice by increasing lipolysis and lipid oxidation in adipose tissue, reducing de novo lipogenesis in the liver, and leading to decreased visceral and liver fat accumulation with improved insulin sensitivity, while maintaining stable levels of insulin and IGF-1.
Review
Endocrinology & Metabolism
Katy A. van Galen, Kasper W. ter Horst, Mireille J. Serlie
Summary: The role of serotonin in food intake is complex, involving both the homeostatic and hedonic brain circuitries. Serotonergic signaling helps integrate metabolic signals to suppress food intake and reduce reward-related consumption, while disturbances in serotonin signaling are associated with obesity. Understanding the regional effects of serotonin receptor subtypes in regulating food intake is crucial for potential therapeutic implications.
Article
Endocrinology & Metabolism
Mohammed Z. Rizwan, Romy Kerbus, Kaj Kamstra, Pramuk Keerthisinghe, Alexander Tups
Summary: Gluten, a major dietary component in western nations, has been found to promote body mass gain and peripheral inflammation in mice. This study investigated the impact of gluten on central inflammation associated with diet-induced obesity. The results showed that gluten had no effect when added to a low-fat diet, but caused increased body mass and adiposity in mice fed a high-fat diet enriched with gluten. Additionally, gluten increased levels of C-reactive protein and resulted in an increase in the number of microglia and astrocytes in the hypothalamus.
JOURNAL OF NEUROENDOCRINOLOGY
(2023)
Review
Endocrinology & Metabolism
Fiona Peris-Sampedro, Marie Le May, Iris Stoltenborg, Erik Schele, Suzanne L. Dickson
Summary: Studies on ghrelin or ghrelin receptor agonists have provided insight into the importance of the brain ghrelin signalling system for physiological processes such as feeding behaviors, growth hormone secretion, and glucose homeostasis. However, there are still unanswered questions about why mouse models with depleted ghrelin signalling do not all exhibit the expected phenotype of skinny dwarfs with behavioral and metabolic problems.
JOURNAL OF NEUROENDOCRINOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Maria P. Cornejo, Emilio R. Mustafa, Daniela Cassano, Jean-Louis Baneres, Jesica Raingo, Mario Perello
Summary: GHSR is a key molecule in neuroendocrine control, regulating various functions such as growth hormone secretion and food intake. Its signaling pathway displays basal constitutive activity and can be regulated by hormones like ghrelin and LEAP2.
Article
Endocrinology & Metabolism
Risa Kimura, Daisuke Kondo, Shota Takemi, Miyuki Fujishiro, Shinji Tsukahara, Takafumi Sakai, Ichiro Sakata
Summary: The study showed that central CRF-R signaling, through the sympathetic-ghrelin pathway, plays a role in maintaining plasma glucose levels in mice under severe calorie restriction.
JOURNAL OF NEUROENDOCRINOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Sara L. Deschaine, Mehdi Farokhnia, Adriana Gregory-Flores, Lia J. Zallar, Zhi-Bing You, Hui Sun, Deon M. Harvey, Renata C. N. Marchette, Brendan J. Tunstall, Bharath K. Mani, Jacob E. Moose, Mary R. Lee, Eliot Gardner, Fatemeh Akhlaghi, Marisa Roberto, James L. Hougland, Jeffrey M. Zigman, George F. Koob, Leandro F. Vendruscolo, Lorenzo Leggio
Summary: Alcohol decreases ghrelin levels in both rats and humans, but this decrease is not in proportion to alcohol's caloric value or through direct interaction with the ghrelin system.
Article
Medicine, Research & Experimental
Kripa Shankar, Shota Takemi, Deepali Gupta, Salil Varshney, Bharath K. Mani, Sherri Osborne-Lawrence, Nathan P. Metzger, Corine P. Richard, Eric D. Berglund, Jeffrey M. Zigman
Summary: Insulin suppresses ghrelin secretion by acting on insulin receptors (IRs) expressed on ghrelin cells, rather than ingested or metabolized macronutrients.
Article
Gastroenterology & Hepatology
Yuki Kobayashi, Shota Takemi, Takafumi Sakai, Chikashi Shibata, Ichiro Sakata
Summary: This study investigated the mechanisms of colonic motility in the house musk suncus as an animal model, finding diurnal changes in colonic motility and a potential gastrocolic reflex. Factors regulating suncus colonic motility were examined, suggesting the suncus could be a novel model for studying colonic motility similar to humans and dogs.
NEUROGASTROENTEROLOGY AND MOTILITY
(2022)
Article
Endocrinology & Metabolism
Deepali Gupta, Anna M. Patterson, Sherri Osborne-Lawrence, Angie L. Bookout, Salil Varshney, Kripa Shankar, Omprakash Singh, Nathan P. Metzger, Corine P. Richard, Steven C. Wyler, Joel K. Elmquist, Jeffrey M. Zigman
Summary: The study investigated the role of acyl-ghrelin on GH secretion and metabolic actions by selectively deleting GHSR from somatotrophs. Results suggest that the direct engagement of GHSR-expressing somatotrophs is essential for acyl-ghrelin to stimulate GH secretion and influence its metabolic actions.
MOLECULAR METABOLISM
(2021)
Article
Endocrinology & Metabolism
Kripa Shankar, Nathan P. Metzger, Omprakash Singh, Bharath K. Mani, Sherri Osborne-Lawrence, Salil Varshney, Deepali Gupta, Sean B. Ogden, Shota Takemi, Corine P. Richard, Karabi Nandy, Chen Liu, Jeffrey M. Zigman
Summary: LEAP2 is an antagonist of GHSR, and its deletion sensitizes mice to ghrelin, resulting in increased food intake and body weight.
MOLECULAR METABOLISM
(2021)
Article
Genetics & Heredity
Shota Takemi, Takashi Miura, Toru Tanaka, Ichiro Sakata
Summary: The Reg3 family of proteins plays critical roles in maintaining host-bacterial homeostasis in the mammalian intestine, with potential additional functions such as attenuating intestinal inflammation. Despite limited knowledge on the regulatory mechanisms of Reg3 protein expression in different organisms, studies on Reg3 alpha in suncus have shown its tissue-specific expression in the pancreas and intestine, suggesting functional conservation. Further investigation into the expression and physiological roles of Reg proteins in other mammals can provide insights into their divergence and evolutionary conservation across species.
Article
Endocrinology & Metabolism
Julieta P. Aguggia, Maria P. Cornejo, Gimena Fernandez, Pablo N. De Francesco, Bharath K. Mani, Daniela Cassano, Agustina Cabral, Spring Valdivia, Guadalupe Garcia Romero, Mirta Reynaldo, Jean-Alain Fehrentz, Jeffrey M. Zigman, Mario Perello
Summary: Recent evidence suggests that Ghrelin may exert some of its actions via the supramammillary nucleus (SuM). In this study, researchers investigated the effects of Ghrelin in the SuM using a GHSR-eGFP mouse model. They found that centrally injected Ghrelin reached the SuM and induced c-Fos expression. Calorie restriction and binge-like eating also had an impact on the SuM cells. However, intra-SuM injected Ghrelin did not have an immediate effect on food intake, locomotor activity, behavioral arousal, or spatial memory but improved recognition memory.
PSYCHONEUROENDOCRINOLOGY
(2022)
Review
Endocrinology & Metabolism
Mario Perello, Suzanne L. Dickson, Jeffrey M. Zigman, Lorenzo Leggio
Summary: The stomach-derived peptide ghrelin, discovered in 1999, is an endogenous agonist of the growth hormone secretagogue receptor (GHSR) and plays key roles in various physiological functions. Its non-acylated form, desacyl-ghrelin, has a less well-understood physiological role. To establish a consistent nomenclature, experts in the field have proposed using the terms ghrelin and desacyl-ghrelin for the hormones, GHSR for the receptor, and LEAP2 for a recently recognized GHSR antagonist/inverse agonist.
JOURNAL OF NEUROENDOCRINOLOGY
(2023)
Article
Neurosciences
Clara Ines McCarthy, Emilio Roman Mustafa, Maria Paula Cornejo, Agustin Yaneff, Silvia Susana Rodriguez, Mario Perello, Jesica Raingo
Summary: The dopamine receptor type 1 (D1R) and type 5 (D5R) exhibit high levels of constitutive activity, which can be modulated by the antipsychotic drug chlorpromazine (CPZ) as an inverse agonist, affecting calcium conductance and neuronal functions in the brain.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Medicine, Research & Experimental
Jing Tian, Lan Guo, Tienju Wang, Kun Jia, Russell H. Swerdlow, Jeffrey M. Zigman, Heng Du
Summary: Studies have found that cognitive decline is often reported in elderly individuals, and hippocampal function declines with age. The plasma levels of LEAP2 and ghrelin were found to change in cognitively normal individuals older than 60. Experiments with aged mice showed that restoring the balance of LEAP2 and ghrelin improved cognitive performance and mitigated age-related hippocampal deficiencies. Therefore, the LEAP2/ghrelin molar ratio may serve as a biomarker for age-related cognitive decline.
Article
Endocrinology & Metabolism
Naho Yokota, Shota Takemi, Ichiro Sakata
Summary: A cyclic rhythmic migrating motor complex (MMC) with three phases exists in the fasting gastrointestinal tract, and phase III contractions propagate from the stomach to the lower intestine. The mechanism of contractions originating in the small intestine during the gastric phase II has not been clarified. This study found that exogenous cholecystokinin (CCK) stimulates contractions of the small intestine via CCK1 receptors, while endogenous CCK is not involved in the strong contractions of small intestinal origin.
GENERAL AND COMPARATIVE ENDOCRINOLOGY
(2023)
Article
Endocrinology & Metabolism
Gimena Fernandez, Pablo N. De Francesco, Maria P. Cornejo, Agustina Cabral, Julieta P. Aguggia, Victor J. Duque, Nilufer Sayar, Sonia Cantel, Juan Burgos, Jean-Alain Fehrentz, Rodrigo Rorato, Deniz Atasoy, Andre S. Mecawi, Mario Perello
Summary: This study provides neuroanatomical and functional characterization of the neuronal types mediating ghrelin actions in the paraventricular nucleus of the hypothalamus. The results suggest that ghrelin mainly acts on neurons expressing nitric oxide synthase 1 (NOS1), and can increase c-Fos expression and phosphorylation of NOS1 in the paraventricular nucleus. Systemically injected ghrelin at a high dose increases ghrelin levels in cerebrospinal fluid and induces activation of a subset of NOS1 neurons in the paraventricular nucleus. Inhibition of nitric oxide production impairs ghrelin-induced calcium increase in corticotropin-releasing hormone neurons and partially impairs the increase of plasma glucocorticoid levels. These findings suggest that ghrelin can directly target specific neurons in the paraventricular nucleus involved in the activation of the hypothalamic-pituitary-adrenal neuroendocrine axis.