Review
Endocrinology & Metabolism
Xuehan Lu, Lili Huang, Zhengxiang Huang, Dandan Feng, Richard J. Clark, Chen Chen
Summary: LEAP-2 functions as an endogenous antagonist of ghrelin and an inverse agonist of GHS-R1a activity, blocking ghrelin's effects on appetite and hormonal secretion. Its levels fluctuate in response to energy status, making it a potential therapeutic target for obesity.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Biochemical Research Methods
Charlotte Cutler, Marjaana Viljanto, Polly Taylor, Jocelyn Habershon-Butcher, Peter Van Eenoo
Summary: This study investigated the metabolism of MK-0677 in horses and identified the best targets for doping control labs. The O-dealkylated metabolite was found to be the most suitable target for detecting MK-0677 administration.
DRUG TESTING AND ANALYSIS
(2022)
Article
Endocrinology & Metabolism
Meng Wang, Yue Zhai, Xiaowei Lei, Jing Xu, Bopei Jiang, Zhe Kuang, Cong Zhang, Shangyun Liu, Shan Bian, Xiao-Mei Yang, Tao Zan, Li-Na Jin, Qingfeng Li, Chao Zhang
Summary: This study investigated the interaction between MRAP2 and MCHR1, and found that MRAP2 could inhibit the signaling of MCHR1. Functional truncation experiments revealed the importance of the C-terminal domains of MRAP2 in pharmacological modulation. These findings elucidated the broad regulatory profile of MRAP2 in the central nervous system.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Neurosciences
Wedad Alhassen, Yuki Kobayashi, Jessica Su, Brianna Robbins, Henry Nguyen, Thant Myint, Micah Yu, Surya M. Nauli, Yumiko Saito, Amal Alachkar
Summary: The MCH system plays a crucial role in regulating the length of brain neuronal primary cilia, with activation causing cilia shortening and inactivation leading to cilia lengthening. This suggests that MCHR1 at primary cilia could be a potential therapeutic target for conditions associated with impaired primary cilia function.
MOLECULAR NEUROBIOLOGY
(2022)
Review
Neurosciences
Cristina Concetti, Denis Burdakov
Summary: The lateral hypothalamus plays a role in sleep-wake control by producing orexin/hypocretin and melanin-concentrating hormone neuropeptides. These neuropeptides can rapidly change their firing in response to external stimuli in awake animals. Optogenetic and chemogenetic manipulations suggest that rapid lateral hypothalamic dynamics shape cognitive and motor processes in the awake brain.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Chemistry, Medicinal
Jozsef Huszar, Eva Bozo, Gyula Beke, Krisztina Katalin Szalai, Peter Kardos, Andras Boros, Istvan Greiner, Janos Eles
Summary: Obesity is a global epidemic associated with severe diseases, and pharmacotherapies including MCHR1 antagonists have been investigated. This study designed and synthesized novel MCHR1 antagonists based on benzofuro-pyridine and pyrazino-indole scaffold, and successfully developed compounds with excellent in vitro parameters that can be considered as valuable tools for further pharmacological investigation.
Article
Neurosciences
Alejandro Lillo, Jaume Lillo, Iu Raich, Cristina Miralpeix, Francesc Dosrius, Rafael Franco, Gemma Navarro
Summary: This article investigates the molecular and functional interactions between cannabinoid CB1 and ghrelin GHS-R1a receptors, showing that they can form macromolecular complexes with specific signaling properties. Results suggest that high-fat diets and treatments with ghrelin or ACEA can upregulate CB1-GHS-R1a receptor complexes in striatal neurons, shedding light on the complexities of neuromodulator interactions in reward circuits.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Behavioral Sciences
Oscar Gonzalez-Flores, James G. Pfaus, Ailyn Luna-Hernandez, Omar Montes-Narvaez, Raymundo Dominguez-Ordonez, Miriam B. Tecamachaltzi-Silvaran, Marcos Garcia-Juarez
Summary: This study aimed to investigate the hypothesis that the Kiss and MCH pathways regulate female sexual behavior induced by steroid hormones. The results showed that the administration of Kiss inhibitor and MCH significantly reduced lordosis behavior induced by hormonal stimulation, supporting the hypothesis.
HORMONES AND BEHAVIOR
(2022)
Article
Neurosciences
Nayna Sanathara, Lamees Alhassen, Ilias Marmouzi, Mohammad Khoudari, Joseph Phan, Wedad Alhassen, Olivier Civelli, Amal Alachkar
Summary: The study identifies a specific role for the oxytocin-MCH pathway in social recognition memory and stereotyped behavior, which are relevant to psychiatric disorders such as schizophrenia and autism.
Article
Multidisciplinary Sciences
Laurie B. Cook, Henry D. Ophardt, Rongkun Shen, Bryan H. Pratt, Lucas A. Galbier
Summary: Understanding adipocyte responsiveness to GPCR-derived signals requires consideration of membrane microenvironments, with specific sub-populations of proteins showing significant variation across regions of the cell. Differentiation from pre-adipocytes to adipocytes involves the development of a transient primary cilium, with the MCH receptor 1 translocating to this structure during early adipogenesis. RNA-Seq analysis reveals that MCH signaling is influenced by its receptor localization, impacting the adipogenic transcriptional program and revealing novel signaling pathways related to circadian rhythm, inflammatory response, and ciliary biogenesis in 3T3-L1 cells. These findings suggest potential unintended consequences of using MCH receptor 1 antagonists for clinical interventions on adipose tissue development.
SCIENTIFIC REPORTS
(2021)
Review
Endocrinology & Metabolism
Ivan C. Alcantara, Ana Pamela Miranda Tapia, Yeka Aponte, Michael J. Krashes
Summary: This Review discusses the advances in neuroscience that have identified brain regions and neural circuits involved in regulating appetite during different phases of eating, including food procurement, food consumption, and meal termination. Studies have found that not only hypothalamic nuclei, but also other brain regions and circuits beyond the hypothalamus, such as the mesolimbic pathway and nodes in the hindbrain, play a role in modulating appetite. Long-term exposure to a calorically dense diet can also alter feeding circuits and the response of motivational systems to food.
Article
Fisheries
Ayaka Senzui, Haruhisa Fukada
Summary: Fish appetite is regulated by orexigenic hormones in a complex manner. A study on yellowtail Seriola quinqueradiata, the most important aquaculture species in Japan, observed the fasting response of appetite-related hormone genes in eight brain regions, and found that appetite regulation may involve brain regions other than the hypothalamus.
Article
Neurosciences
Shuntaro Izawa, Takeshi Yoneshiro, Kunio Kondoh, Shohei Nakagiri, Yuko Okamatsu-Ogura, Akira Terao, Yasuhiko Minokoshi, Akihiro Yamanaka, Kazuhiro Kimura
Summary: Research indicates that mice with ablated MCH neurons have reduced body weight, increased BAT activity, and higher energy expenditure, suggesting that MCH neurons negatively modulate energy expenditure through modulating BAT activity. The study also suggests that MCH neurons may suppress BAT activity by providing inhibitory input to MRN neurons.
JOURNAL OF PHYSIOLOGY-LONDON
(2022)
Article
Neurosciences
Victoria Linehan, Michiru Hirasawa
Summary: Orexin and MCH neurons display different activation patterns during fasting, with orexin neurons primarily functioning in the later stage of fasting to promote arousal and foraging behaviors, while MCH neurons are preferentially activated in the early stage of fasting to protect against weight loss. This alternating activation of these neuron groups may optimize energy balance during ongoing fasting.
Review
Biochemistry & Molecular Biology
Magdalena Sustkova-Fiserova, Chrysostomos Charalambous, Anna Khryakova, Alina Certilina, Marek Lapka, Romana Slamberova
Summary: Drug addiction causes serious health, social, and economic burdens. Current drug dependence treatment options are limited and unreliable, leading to the need for new and more effective strategies. The antagonism of the growth hormone secretagogue receptor type A (GHS-R1A) has emerged as a potential treatment for addiction and has been studied extensively. This review provides an overview of preclinical and clinical studies on the involvement of ghrelin's/GHS-R1A in the reinforcing effects and addiction of non-alcohol drugs. Further research is needed to understand the mechanisms involved and to evaluate the potential utilization and safety of GHS-R1A antagonism in drug addiction therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Erik Schele, Daniela M. Pfabigan, Joel Simren, Uta Sailer, Suzanne L. Dickson
Article
Behavioral Sciences
Philibert Duriez, Sabiha Eddarkaoui, David Blum, Suzanne L. Dickson, Philip Gorwood, Virginie Tolle, Odile Viltart
HORMONES AND BEHAVIOR
(2020)
Article
Endocrinology & Metabolism
Tina Bake, Marie V. Le May, Christian E. Edvardsson, Heike Vogel, Ulrika Bergstrom, Marjorie Nicholson Albers, Karolina P. Skibicka, Imre Farkas, Zsolt Liposits, Suzanne L. Dickson
Article
Neurosciences
Kathy C. G. de Git, Esther M. Hazelhoff, Minke H. C. Nota, Erik Schele, Mieneke C. M. Luijendijk, Suzanne L. Dickson, Geoffrey van der Plasse, Roger A. H. Adan
Summary: Both Zona Incerta (ZI) and Ventral Tegmental Area (VTA) play key roles in feeding behavior, with ZI neurons projecting to the VTA having a bidirectional influence on feeding behavior by facilitating action initiation towards food without affecting overall activity levels.
JOURNAL OF PHYSIOLOGY-LONDON
(2021)
Article
Neurosciences
Azar Omrani, Veronne A. J. de Vrind, Bart Lodder, Iris Stoltenborg, Karlijn Kooij, Inge G. Wolterink-Donselaar, Mieneke C. M. Luijendijk-Berg, Keith M. Garner, Lisanne J. van't Sant, Annemieke Rozeboom, Suzanne L. Dickson, Frank J. Meye, Roger A. H. Adan
Summary: The study identified that leptin targets multiple inputs to the dopamine system to reduce food reward seeking. Leptin enhances the activity of GABA neurons in the VTA, inhibiting dopamine neurons projecting to the nucleus accumbens. Additionally, lateral hypothalamic LepR-expressing neurons indirectly modulate dopamine neurons and increase motivation for food reward only in mice in positive energy balance.
BIOLOGICAL PSYCHIATRY
(2021)
Article
Endocrinology & Metabolism
John-Olov Jansson, Adria Dalmau Gasull, Erik Schele, Suzanne L. Dickson, Vilborg Palsdottir, Anders Palmquist, Ferran Font Girones, Jakob Bellman, Fredrik Anesten, Daniel Hagg, Claes Ohlsson
Summary: The study found that increased artificial loading affects the growth and development of animals, and this effect is related to body weight sensing mechanisms, which may regulate the somatotropic axis to maintain the individual specific growth channel.
Article
Neurosciences
Marie Le May, Fiona Peris-Sampedro, Iris Stoltenborg, Erik Schele, Tina Bake, Roger A. H. Adan, Suzanne L. Dickson
Summary: Studies have shown that GHSR cells in the lateral parabrachial nucleus play a crucial role in regulating diet-induced weight gain and adiposity, as well as food intake and food choice. These cells are predominantly glutamatergic and do not belong to the well-characterized anorexigenic CGRP cell population.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Multidisciplinary Sciences
Jan M. Bauer, Marina Schroder, Martina Vecchi, Tina Bake, Suzanne L. Dickson, Michele Belot
Summary: The study found that using sweet foods as rewards can make children value these foods more, leading to increased calorie intake, which may not be beneficial for health.
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)
Article
Endocrinology & Metabolism
Tina Bake, Fiona Peris-Sampedro, Zita Waczek, Claes Ohlsson, Vilborg Palsdottir, John-Olov Jansson, Suzanne L. Dickson
Summary: The research findings suggest that weight loading affects metabolic outcomes in obese and lean rats, with a more pronounced protective effect in obese rats and the ability to improve insulin sensitivity impairments. Additionally, weight loading reduces caloric intake in obese rats, decreases meal size, decreases dark phase activity, and increases meal frequency in lean rats.
JOURNAL OF NEUROENDOCRINOLOGY
(2021)
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)
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)
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
Clinical Neurology
Erik Schele, Iris Stoltenborg, Anders Xie, Fiona Peris-Sampedro, Roger A. H. Adan, Suzanne L. Dickson
Summary: This study aims to investigate the activation of orexin neurons during severe anorectic state and the potential of suvorexant, a dual orexin receptor antagonist, in reducing excessive physical activity. The findings indicate that a large population of orexin neurons are activated in the ABA mouse model and that peripheral administration of suvorexant decreases food anticipatory activity. Orexin may be a suitable target for treating hyperactivity in AN, and further research is recommended to examine the efficacy of suvorexant in aiding AN patients in controlling excessive activity.
EUROPEAN NEUROPSYCHOPHARMACOLOGY
(2023)
Article
Psychology, Biological
D. M. Pfabigan, E. R. Frogner, E. Schele, P. M. Thorsby, B. S. Skalhegg, S. L. Dickson, U. Sailer
Summary: Variations in ghrelin concentrations may affect the processing of touch as a social reward in humans, with higher ghrelin concentrations associated with a lower reward value for touch.
