Melanocortin-5 Receptor: Pharmacology and Its Regulation of Energy Metabolism

Ji, Liqin; Hong, Ye; Tao, Ya-Xiong

doi:10.3390/ijms23158727

Cited by 8 publications

(4 citation statements)

References 170 publications

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“…Moreover, activated MC5R can stimulate lipid mobilization in adipocytes and glucose uptake in skeletal muscle [35]. It has been shown that the binding of α-MSH to MC5R activates the PKA and ERK1/2 (MAPK) signaling pathways, and the activation of MC5R in skeletal muscle regulates fatty acids oxidation in muscle cells through PKA and MAPK signaling pathways [36].…”

Section: Discussionmentioning

confidence: 99%

Study on the Mechanism of MC5R Participating in Energy Metabolism of Goose Liver

Zhang

Xing

et al. 2023

IJMS

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Nutrition and energy levels have an important impact on animal growth, production performance, disease occurrence and health recovery. Previous studies indicate that melanocortin 5 receptor (MC5R) is mainly involved in the regulations of exocrine gland function, lipid metabolism and immune response in animals. However, it is not clear how MC5R participates in the nutrition and energy metabolism of animals. To address this, the widely used animal models, including the overfeeding model and the fasting/refeeding model, could provide an effective tool. In this study, the expression of MC5R in goose liver was first determined in these models. Goose primary hepatocytes were then treated with nutrition/energy metabolism-related factors (glucose, oleic acid and thyroxine), which is followed by determination of MC5R gene expression. Moreover, MC5R was overexpressed in goose primary hepatocytes, followed by identification of differentially expressed genes (DEGs) and pathways subjected to MC5R regulation by transcriptome analysis. At last, some of the genes potentially regulated by MC5R were also identified in the in vivo and in vitro models, and were used to predict possible regulatory networks with PPI (protein–protein interaction networks) program. The data showed that both overfeeding and refeeding inhibited the expression of MC5R in goose liver, while fasting induced the expression of MC5R. Glucose and oleic acid could induce the expression of MC5R in goose primary hepatocytes, whereas thyroxine could inhibit it. The overexpression of MC5R significantly affected the expression of 1381 genes, and the pathways enriched with the DEGs mainly include oxidative phosphorylation, focal adhesion, ECM–receptor interaction, glutathione metabolism and MAPK signaling pathway. Interestingly, some pathways are related to glycolipid metabolism, including oxidative phosphorylation, pyruvate metabolism, citrate cycle, etc. Using the in vivo and in vitro models, it was demonstrated that the expression of some DEGs, including ACSL1, PSPH, HMGCS1, CPT1A, PACSIN2, IGFBP3, NMRK1, GYS2, ECI2, NDRG1, CDK9, FBXO25, SLC25A25, USP25 and AHCY, was associated with the expression of MC5R, suggesting these genes may mediate the biological role of MC5R in these models. In addition, PPI analysis suggests that the selected downstream genes, including GYS2, ECI2, PSPH, CPT1A, ACSL1, HMGCS1, USP25 and NDRG1, participate in the protein–protein interaction network regulated by MC5R. In conclusion, MC5R may mediate the biological effects caused by changes in nutrition and energy levels in goose hepatocytes through multiple pathways, including glycolipid-metabolism-related pathways.

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Section: Discussionmentioning

confidence: 99%

Study on the Mechanism of MC5R Participating in Energy Metabolism of Goose Liver

Zhang

Xing

et al. 2023

IJMS

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“…Melanocortins are derived from tissue-specific posttranslational processing of the common precursor—proopiomelanocortin (POMC) [ 2 ]. The melanocortins are involved in pleiotropic physiological functions, including pigmentation, adrenal steroidogenesis, appetite regulation and energy homeostasis, energy metabolism, cardiovascular function, exocrine secretion, inflammation, immunomodulation, neuromuscular regeneration, sexual function, and temperature control [ 3 , 4 , 5 , 6 , 7 , 8 ]. Recent FDA approval of melanocortin-based drugs is expected to further promote the investigation of the melanocortin system and lead to new pharmacotherapies.…”

Section: Introductionmentioning

confidence: 99%

Ligands for Melanocortin Receptors: Beyond Melanocyte-Stimulating Hormones and Adrenocorticotropin

Yuan

Tao

2022

Biomolecules

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The discovery of melanocortins in 1916 has resulted in more than 100 years of research focused on these peptides. Extensive studies have elucidated well-established functions of melanocortins mediated by cell surface receptors, including MSHR (melanocyte-stimulating hormone receptor) and ACTHR (adrenocorticotropin receptor). Subsequently, three additional melanocortin receptors (MCRs) were identified. Among these five MCRs, MC3R and MC4R are expressed primarily in the central nervous system, and are therefore referred to as the neural MCRs. Since the central melanocortin system plays important roles in regulating energy homeostasis, targeting neural MCRs is emerging as a therapeutic approach for treating metabolic conditions such as obesity and cachexia. Early efforts modifying endogenous ligands resulted in the development of many potent and selective ligands. This review focuses on the ligands for neural MCRs, including classical ligands (MSH and agouti-related peptide), nonclassical ligands (lipocalin 2, β-defensin, small molecules, and pharmacoperones), and clinically approved ligands (ACTH, setmelanotide, bremelanotide, and several repurposed drugs).

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“…As a single transmembrane protein that forms a homodimer, MRAPs may interact with and regulate the trafficking and signaling of all MCRs ( Chan et al, 2009 ). In numerous vertebrates, MCRs interact with MRAPs and play a role in pigmentation, lipolysis, adrenal steroidogenesis, energy homeostasis, immunology, and cardiovascular function ( Cooray and Clark, 2011 ; Dores et al, 2016 ; Scanes and Pierzchala-Koziec, 2021 ; Ji et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Characterization of the chicken melanocortin 5 receptor and its potential role in regulating hepatic glucolipid metabolism

Zhang

Huang

et al. 2022

Front. Physiol.

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Melanocortin receptors (MC1R-MC5R) and their accessory proteins (MRAPs) are involved in a variety of physiological processes, including pigmentation, lipolysis, adrenal steroidogenesis, and immunology. However, the physiological roles of MC5R are rarely characterized in vertebrates, particularly in birds. In this work, we cloned the full-length cDNA of chicken MC5R and identified its core promoter region. Functional studies revealed that cMC5R was more sensitive to ACTH/α-MSH than β-MSH/γ-MSH, and was coupled to the cAMP/PKA signaling pathway. We demonstrated that MRAP2 decreased MC5R sensitivity to α-MSH, whereas MRAP1 did not have a similar effect, and that both MRAPs significantly reduced MC5R expression on the cell membrane surface. Transcriptome and qPCR data showed that both MRAP1 and MC5R were highly expressed in chicken liver. Additionally, we observed that ACTH might increase hepatic glucose production and decrease lipogenesis in primary hepatocytes, and dose-dependently downregulated the expression levels of ELOVL6 and THRSPA genes. These findings indicated that ACTH may act directly on hepatocytes to regulate glucolipid metabolism, which will help to understand the function of MC5R in avian.

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Melanocortin-5 Receptor: Pharmacology and Its Regulation of Energy Metabolism

Cited by 8 publications

References 170 publications

Study on the Mechanism of MC5R Participating in Energy Metabolism of Goose Liver

Study on the Mechanism of MC5R Participating in Energy Metabolism of Goose Liver

Ligands for Melanocortin Receptors: Beyond Melanocyte-Stimulating Hormones and Adrenocorticotropin

Characterization of the chicken melanocortin 5 receptor and its potential role in regulating hepatic glucolipid metabolism

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