Article
Cell Biology
Meng Wang, Yue Zhai, Liumei Lu, Cong Zhang, Na Li, Song Xue, Daofu Cheng, Shaliu Fu, Qi Liu, Chao Zhang
Summary: This study revealed the bidirectional homo- and hetero-dimeric topologies of two zebrafish MRAP2 isoforms on the plasma membrane, investigated their regulatory roles on MC4R signaling, and identified the carboxyl terminal as the functional domain.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Nutrition & Dietetics
Samantha M. Fortin, Jack Chen, Harvey J. Grill, Matthew R. Hayes
Summary: The Mes5 expresses the melanocortin-4 receptor and its activation can suppress food intake and body weight in mice. NTS POMC neurons projecting to Mes5 can be chemogenetically activated to drive a suppression in food intake, highlighting a novel circuit for modulating food intake and body weight.
Article
Endocrinology & Metabolism
Xiaozhu Wang, Song Xue, Xiaowei Lei, Wenqi Song, Lei Li, Xuan Li, Yanbin Fu, Cong Zhang, Hailin Zhang, Yao Luo, Meng Wang, Gufa Lin, Chao Zhang, Jing Guo
Summary: In this study, the researchers investigated the role of MRAP2 in the regulation of central melanocortin signaling in the Mexican axolotl. They found that the conservation of axolotl mc3r and mc4r is higher than mrap2, and the axolotl MC3R/MC4R is closer to their counterparts in the clawed frog. The researchers also confirmed the co-expression and functional complex formation of axolotl MC3R/MC4R and MRAP2 on the plasma membrane.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Endocrinology & Metabolism
Meng Wang, Linyu Pi, Xiaowei Lei, Lei Li, Jing Xu, Zhe Kuang, Cong Zhang, Liang Li, Chao Zhang
Summary: The study modified the structure of MRAP2 and generated six distinct conformational variants, demonstrating the importance of the orientation of each domain for MRAP2 function and its regulatory effects on MC4R.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Psychology, Biological
Rachel A. Ross, Angela Kim, Priyanka Das, Yan Li, Yong Kee Choi, Andy Thompson, Ella Douglas, Siva Subramanian, Kat Ramos, Kathryn Callahan, Vadim Y. Bolshakov, Kerry J. Ressler
Summary: A novel population of MC4R-expressing neurons in the infralimbic region of the prefrontal cortex is found to be associated with food intake and body weight regulation in male mice. These neurons receive input from melanocortinergic neurons and project to regions involved in appetitive responses to food-related stimuli.
PHYSIOLOGY & BEHAVIOR
(2023)
Article
Multidisciplinary Sciences
William C. Krause, Ruben Rodriguez, Bruno Gegenhuber, Navneet Matharu, Andreas N. Rodriguez, Adriana M. Padilla-Roger, Kenichi Toma, Candice B. Herber, Stephanie M. Correa, Xin Duan, Nadav Ahituv, Jessica Tollkuhn, Holly A. Ingraham
Summary: Depletion of estrogen leads to inactivity, fat accumulation, and diabetes in rodents and humans. Research has found that estrogen-sensitive neurons in the brain play a role in rebalancing energy allocation in female mice, with implications for metabolism and physical activity. Melanocortin-4 receptor signaling extends beyond regulation of food intake, impacting physical activity levels and offering potential targets for intervention in obesity.
Article
Biology
Jing Xu, Meng Wang, Yanbin Fu, Cong Zhang, Zhe Kuang, Shan Bian, Rui Wan, Shen Qu, Chao Zhang
Summary: By reversing the wild-type MRAP2 protein sequences, researchers created novel functional modulators for regulating MC4R signaling. The reversed MRAP2 proteins demonstrated proper topology and interaction with MC4R signaling in mice and zebrafish. These findings provide important insights for the development of therapeutic drugs for MC4R-related disorders.
Article
Biochemistry & Molecular Biology
Maria Rosaria Fullone, Daniela Maftei, Martina Vincenzi, Roberta Lattanzi, Rossella Miele
Summary: This study aimed to analyze the functional role of the specific arginine residue at position 125 of MRAP2, and found that it affects protein conformation, dimer formation, and PKR2 binding. This helps in understanding the regulation mechanism of MRAP2 on G protein-coupled receptors and further revealing metabolic pathways associated with metabolic dysfunction.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Pharmacology & Pharmacy
Vanni Caruso, Mariachiara Zuccarini, Patrizia Di Iorio, Ishaq Muhammad, Maurizio Ronci
Summary: This review discusses the molecular mechanisms leading to changes in feeding behavior within hypothalamic neurons following purinergic receptor activation, emphasizes the importance of purinergic signaling in metabolic homeostasis, and explores the possibility of targeting its receptors for therapeutic purposes.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Oncology
Meng Wang, Xiaozhu Wang, Bopei Jiang, Yue Zhai, Jihong Zheng, Liu Yang, Xiaolu Tai, Yunpeng Li, Shaliu Fu, Jing Xu, Xiaowei Lei, Zhe Kuang, Cong Zhang, Xuanxuan Bai, Mingyu Li, Tao Zan, Shen Qu, Qingfeng Li, Chao Zhang
Summary: The study comprehensively elucidated the GPCR networks and associated MRAP protein networks in two major endocrine organs at single-cell resolution. The results identified 36 metabolic-related GPCRs as novel interacting partners of MRAP1 and 46 metabolic-related GPCRs as novel interacting partners of MRAP2. The study also demonstrated the importance of MRAP2 in regulating feeding behavior and body weight in mice.Overall,this study has significant implications for understanding the phenotyping investigation of GPCR-MRAP functional complexes.
CLINICAL AND TRANSLATIONAL MEDICINE
(2022)
Article
Multidisciplinary Sciences
Yu Yong, Isin Cakir, Pauline Lining Pan, Jessica E. Biddinger, Rebecca J. Bluett, Ken Mackie, Nathan Bingham, Sachin Patel, Masoud Ghamari-Langroudi
Summary: This passage discusses the importance of hypothalamic regulation of feeding and energy expenditure, as well as the roles of melanocortins and endogenous cannabinoids in these processes. The study shows that 2-AG regulates MC4R cell activity by inhibiting GABA input, impacting energy state, body weight, appetite, and energy expenditure.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Maria Rosaria Fullone, Daniela Maftei, Martina Vincenzi, Roberta Lattanzi, Rossella Miele
Summary: Melanocortin Receptor Accessory Protein 2 (MRAP2) regulates the trafficking and signal transduction of G-protein-coupled receptors (GPCRs) involved in energy homeostasis, and its interaction with PKR2 plays a crucial role in modulating receptor localization and signaling. The prokineticin transduction system also regulates MRAP2 expression, highlighting its importance in the control of food intake.
Article
Medicine, Research & Experimental
Yi Wang, Adelaide Bernard, Fanny Comblain, Xinyu Yue, Christophe Paillart, Sumei Zhang, Jeremy F. Reiter, Christian Vaisse
Summary: The MC4R expressed in cilia of neurons in the hypothalamus plays a crucial role in controlling food intake and body weight. Cilia are essential for the anorexigenic effect of pharmacological activators of MC4R. Defects in ciliary localization of MC4R may contribute to obesity in human genetic obesity syndromes and ciliopathies.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
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
Immunology
Li Li, Eun-Seon Yoo, Xiujuan Li, Steven C. Wyler, Xiameng Chen, Rong Wan, Amanda G. Arnold, Shari G. Birnbaum, Lin Jia, Jong-Woo Sohn, Chen Liu
Summary: Atypical antipsychotics like risperidone and olanzapine can cause drug-induced metabolic syndrome by inhibiting hypothalamic Mc4r neuronal activity, leading to hyperphagia and weight gain.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Avinaash Maharaj, Ashwini Maudhoo, Li F. Chan, Tatiana Novoselova, Rathi Prasad, Louise A. Metherell, Leonardo Guasti
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2019)
Review
Endocrinology & Metabolism
Adrian J. L. Clark, Li Chan
FRONTIERS IN ENDOCRINOLOGY
(2019)
Editorial Material
Cell Biology
Jung Dae Kim, Sabrina Diano
Article
Biochemistry & Molecular Biology
A. Maharaj, J. Williams, T. Bradshaw, T. Guran, D. Braslavsky, J. Casas, L. F. Chan, L. A. Metherell, R. Prasad
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2020)
Article
Cell Biology
Giuseppe Bruschetta, Sungho Jin, Zhong-Wu Liu, Jung Dae Kim, Sabrina Diano
Article
Biology
Sungho Jin, Nal Ae Yoon, Zhong-Wu Liu, Jae Eun Song, Tamas L. Horvath, Jung Dae Kim, Sabrina Diano
Summary: The study reveals that mitochondrial dynamics and fatty acids oxidation in hypothalamic AgRP neurons play a critical role in AgRP neuronal function and body-weight regulation. Mice lacking Dnm1l in adult AgRP neurons showed decreased fasting-induced AgRP neuronal activity and feeding, as well as a significant decrease in body weight, fat mass, and feeding. This suggests that mitochondrial fission and fatty acid utilization are important mechanisms for energy homeostasis and weight regulation.
Article
Multidisciplinary Sciences
Hadar Israeli, Oksana Degtjarik, Fabrizio Fierro, Vidicha Chunilal, Amandeep Kaur Gill, Nicolas J. Roth, Joaquin Botta, Vadivel Prabahar, Yoav Peleg, Li F. Chan, Danny Ben-Zvi, Peter J. McCormick, Masha Y. Niv, Moran Shalev-Benami
Summary: This study elucidated the mechanism of MC4R activation, identified a molecular switch for initiating satiation signaling, and suggested the involvement of calcium in agonist efficacy. These findings may guide the design of future weight-management drugs.
Article
Health Care Sciences & Services
R. Asaad Baksh, Andre Strydom, Sarah E. Pape, Li F. Chan, Martin C. Gulliford
Summary: This study found that individuals with Down syndrome are more susceptible to being diagnosed with COVID-19, especially those with chronic respiratory diseases. Therefore, they are particularly vulnerable during viral pandemics and should be prioritized for vaccinations.
JOURNAL OF GENERAL INTERNAL MEDICINE
(2022)
Article
Pediatrics
Christopher M. Parry, Li F. Chan, Daniel F. Carr, Daniel B. Hawcutt
Summary: PDGFD is expressed in the human adrenal cell line, H295R, and its expression can be influenced by beclometasone and steroidogenesis agonists/antagonists. This study provides in vitro evidence supporting a potential link between the PDGF and cortisol production pathways, indicating that PDGFD variants may impact an individual's sensitivity to corticosteroid-induced adrenal suppression.
PEDIATRIC RESEARCH
(2023)
Article
Multidisciplinary Sciences
Cristina Perez-Ternero, Aisah A. Aubdool, Raj Makwana, Gareth J. Sanger, Roland H. Stimson, Li F. Chan, Amie J. Moyes, Adrian J. Hobbs
Summary: C-type natriuretic peptide (CNP) plays a crucial role in lipid homeostasis and energy balance by regulating the expression of uncoupling protein-1 and lipid utilization. CNP exerts these metabolic regulatory actions by inhibiting sympathetic thermogenic programming and reducing peroxisome proliferator-activated receptor-gamma coactivator-1 alpha expression, while driving adipogenesis via NPR-B/protein kinase-G.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Endocrinology & Metabolism
Aisha A. Aslam, R. Asaad Baksh, Sarah E. Pape, Andre Strydom, Martin C. Gulliford, Li F. Chan
Summary: Individuals with Down syndrome have a higher incidence of diabetes, especially at a younger age. Obesity is associated with an increased risk of type 2 diabetes in individuals with Down syndrome.
Article
Endocrinology & Metabolism
Rachel Forfar, Mashal Hussain, Puneet Khurana, Jennifer Cook, Steve Lewis, Dillon Popat, David Jackson, Ed McIver, Jeff Jerman, Debra Taylor, Adrian J. L. Clark, Li F. Chan
Summary: The overproduction of ACTH leads to significant morbidity, but there is currently no effective medical treatment to directly block its action. This study identified a highly specific MC2R antagonist, providing a foundation for the clinical investigation of small-molecule ACTH antagonists as therapeutic agents.
ENDOCRINE CONNECTIONS
(2022)
Article
Endocrinology & Metabolism
Valeria Hasenmajer, Rosario Ferrigno, Marianna Minnetti, Bianca Pellegrini, Andrea M. Isidori, Andrea Lenzi, Mariacarolina Salerno, Marco Cappa, Li Chan, Maria Cristina De Martino, Martin O. Savage
Summary: Adrenal insufficiency is a severe endocrine disorder characterized by insufficient secretion of glucocorticoid and/or mineralocorticoid due to impaired adrenal function or inadequate adrenal stimulation. This review focuses on rare genetic causes of primary adrenal insufficiency with isolated glucocorticoid or combined glucocorticoid and mineralocorticoid deficiencies, as well as rare syndromes of isolated mineralocorticoid deficiency. The diagnosis of these rare genetic forms of pediatric adrenal insufficiency is challenging due to their clinical heterogeneity and rarity, and this review aims to provide an overview of their genetic and clinical features, as well as diagnostic and therapeutic approaches.
REVIEWS IN ENDOCRINE & METABOLIC DISORDERS
(2023)
Article
Public, Environmental & Occupational Health
R. Asaad Baksh, Sarah E. Pape, Li F. Chan, Aisha A. Aslam, Martin C. Gulliford, Andre Strydom
Summary: This study comprehensively estimated the risk of multiple morbidity across the lifespan in people with Down syndrome and identified syndrome-specific health conditions. The results showed that people with Down syndrome had an increased risk of dementia, hypothyroidism, epilepsy, and haematological malignancy, while asthma, cancer, ischaemic heart disease, and hypertension were less frequent. Compared to people with other intellectual disabilities, people with Down syndrome had higher risks of dementia, hypothyroidism, obstructive sleep apnoea, and haematological malignancy, with reduced rates for a third of conditions. The morbidities in Down syndrome could be categorized based on age-related incidence trajectories and clustered into typical syndromic conditions, cardiovascular diseases, autoimmune disorders, and mental health conditions.
LANCET PUBLIC HEALTH
(2023)
Article
Endocrinology & Metabolism
Federica Buonocore, Avinaash Maharaj, Younus Qamar, Katrin Koehler, Jenifer P. Suntharalingham, Li F. Chan, Bruno Ferraz-de-Souza, Claire R. Hughes, Lin Lin, Rathi Prasad, Jeremy Allgrove, Edward T. Andrews, Charles R. Buchanan, Tim D. Cheetham, Elizabeth C. Crowne, Justin H. Davies, John W. Gregory, Peter C. Hindmarsh, Tony Hulse, Nils P. Krone, Pratik Shah, M. Guftar Shaikh, Catherine Roberts, Peter E. Clayton, Mehul T. Dattani, N. Simon Thomas, Angela Huebner, Adrian J. Clark, Louise A. Metherell, John C. Achermann
Summary: Genetic causes of primary adrenal insufficiency in children and young people were investigated in a cohort of 155 individuals in the UK, with 66.5% receiving a genetic diagnosis. Pathogenic variants were identified in 11 genes, highlighting the importance of genetic testing in defining the cause of PAI. Age at presentation, treatment, ancestral background, and birth weight can provide diagnostic clues, but genetic testing is often necessary for accurate diagnosis.
JOURNAL OF THE ENDOCRINE SOCIETY
(2021)
Article
Endocrinology & Metabolism
Liujun Chen, Lisha Li, Donghong Cui, Yiheng Huang, Haibin Tong, Haleh Zabihi, Shuxia Wang, Yadan Qi, Ted Lakowski, Lin Leng, Suixin Liu, Hong Wu, Lawrence H. Young, Richard Bucala, Dake Qi
Summary: Attenuation of adipose hormone sensitive lipase (HSL) may impair lipolysis and exacerbate obesity. Cytokine macrophage migration inhibitory factor (MIF) plays a role in regulating adipose HSL and adipocyte hypertrophy. Both intracellular and extracellular MIF have opposing effects on HSL, but extracellular action predominates to downregulate HSL and exacerbate obesity development during high-fat diet (HFD).
MOLECULAR METABOLISM
(2024)
Article
Endocrinology & Metabolism
Mengyang Tang, Yi Zhang, Rong Zhang, Yuemei Zhang, Jiangfei Zheng, Daixi Wang, Xinyu Wang, Jing Yan, Cheng Hu
Summary: This study aimed to explore the role of GPSM1 in POMC neurons and the underlying mechanisms in metabolic homeostasis. Through various molecular, biochemical, immunofluorescent, immunohistochemical analyses, and cell culture studies, the study revealed the pathophysiological role of GPSM1 in POMC neurons and its regulation of POMC neuron activity.
MOLECULAR METABOLISM
(2024)