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
Biochemistry & Molecular Biology
Yuki Kobayashi, Tomoya Okada, Daisuke Miki, Yuko Sekino, Noriko Koganezawa, Tomoaki Shirao, Giovanne B. Diniz, Yumiko Saito
Summary: The primary cilium is a sensitive signaling hub in cells, capable of changing length to ensure efficient signaling capacity. In hippocampal neurons, MCH triggers cilia length reduction via MCHR1-mediated Gi/o and Akt signaling pathways.
NEUROCHEMISTRY INTERNATIONAL
(2021)
Article
Biochemistry & Molecular Biology
Gyutae Lim, Ka Young You, Jeong Hyun Lee, Moon Kook Jeon, Byung Ho Lee, Jae Yong Ryu, Kwang-Seok Oh
Summary: This study identified a potent MCHR1 antagonist, KRX-104130, with no cardiotoxicity using machine learning prediction models. The study also explored the potential of KRX-104130 for treating nonalcoholic steatohepatitis (NASH) and confirmed its therapeutic effects in a NASH mouse model.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(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
Fisheries
Haruhisa Fukada, Noriko Hosomi, Haruka Morino, Toshiro Masumoto
Summary: The results of two experiments suggest that the levels of NPY and MCH1 in yellowtail are mainly regulated by serum glucose concentration derived from feed, and they function as feeding stimulators.
Article
Pharmacology & Pharmacy
Xiaoman He, Yuhang Li, Nana Zhang, Jinfang Huang, Xing Ming, Ruixiao Guo, Yang Hu, Pengfei Ji, Feifei Guo
Summary: The melanin-concentrating hormone (MCH) neurons in the lateral hypothalamic area (LHA) project to the basolateral amygdala (BLA) and play a role in regulating anxiety-like behavior in mice. Chronic acute combining stress (CACS) leads to anxiety-like behavior and intestinal dysfunction, which can be improved by blocking MCH receptor 1 (MCHR1) and regulating intestinal permeability and inflammation.
FRONTIERS IN PHARMACOLOGY
(2022)
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
Multidisciplinary Sciences
Ji-Yeun Park, Seong-Jin Cho, Soon-Ho Lee, Yeonhee Ryu, Jae-Hwan Jang, Seung-Nam Kim, Hi-Joon Park
Summary: This study identified that peripheral ERK activation by acupuncture plays a key role in initiating acupuncture-induced peripheral proteomic changes, and the brain functional connectivity alterations caused by acupuncture mainly affect the hypothalamus and arcuate nucleus. Additionally, the posterior hypothalamus showed the highest betweenness centrality in brain functional connectivity changes after acupuncture.
SCIENTIFIC REPORTS
(2021)
Article
Neurosciences
Ronald McGregor, Alessandra Matzeu, Thomas C. Thannickal, Frank Wu, Marcia Cornford, Remi Martin-Fardon, Jerome M. Siegel
Summary: Heroin addicts and mice administered morphine for a 2 week period demonstrated an increase in hypothalamic hypocretin (Hcrt or orexin) producing neurons, while also showing a decrease in Hcrt cell size. Similarly, male rats addicted to cocaine showed an increased number of detectable Hcrt neurons. On the other hand, humans with alcohol use disorder (AUD) exhibited a decrease in the number and size of detectable Hcrt neurons, as well as a reduction in the size of intermingled melanin concentrating hormone (MCH) neurons. The present study highlights significant differences in the response of Hcrt neurons to opioids and alcohol in individuals with substance abuse history.
Review
Biochemistry & Molecular Biology
Hyejin Park, Un-Ho Jin, Gregory Martin, Robert S. Chapkin, Laurie A. Davidson, Kyongbum Lee, Arul Jayaraman, Stephen Safe
Summary: Unsubstituted flavone can induce gene expression in Caco2 cells and acts as an AhR agonist. The addition of hydroxyl groups can determine the activity of flavones, but the affinity of mono- and dihydroxyflavones to AhR is similar and cannot accurately predict their activity. Most AhR-inactive flavones also function as AhR antagonists.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Clinical Neurology
Vicente Ruiz-Viroga, Marialuisa de Ceglia, Laura Morelli, Eduardo M. Castano, Eduardo Blanco Calvo, Juan Suarez, Fernando Rodriguez de Fonseca, Pablo Galeano, Patricia Lagos
Summary: Interest in the role of melanin-concentrating hormone (MCH) in memory processes has grown, but studies have provided contradictory findings. This study investigated the effects of MCH on memory consolidation and the BDNF/TrkB system. The results showed that high doses of MCH impaired memory consolidation, but this effect could be reversed by a co-administration with the MCHR-1 antagonist ATC-0175. Additionally, MCH decreased the expression of MCHR-1 and TrkB, linking both endogenous systems to memory processes.
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
(2023)
Article
Biochemistry & Molecular Biology
Jyoti Kumbar, C. B. Ganesh
Summary: The study revealed that melanin-concentrating hormone (MCH) blocks follicular development during the ovarian cycle in female tilapia Oreochromis mossambicus, possibly through the suppression of the GnRH-LH axis, and may activate the stress-axis pathway in fish.
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR & INTEGRATIVE PHYSIOLOGY
(2022)
Article
Endocrinology & Metabolism
Yukari Shinohara, Satoshi Kasagi, Noriko Amiya, Yukihiro Hoshino, Ryo Ishii, Noriyuki Hyodo, Hiroaki Yamaguchi, Shoh Sato, Masafumi Amano, Akiyoshi Takahashi, Kanta Mizusawa
Summary: This study investigates the mechanism of skin color regulation in koi carp and reveals the differences in skin coloration response to background color between koi carp and common carp. The findings suggest that the weak sensitivity of scale melanophores to MCH and adrenaline may be responsible for the lack of skin color change in koi carp.
FRONTIERS IN ENDOCRINOLOGY
(2022)