Dataset Information

Melanocortin Receptor 4 (MC4R) Signaling System in Nile Tilapia.

ABSTRACT: The melanocortin receptor 4 (MC4R) signaling system consists of MC4R, MC4R ligands [melanocyte-stimulating hormone (MSH), adrenocorticotropin (ACTH), agouti-related protein (AgRP)], and melanocortin-2 receptor accessory protein 2 (MRAP2), and it has been proposed to play important roles in feeding and growth in vertebrates. However, the expression and functionality of this system have not been fully characterized in teleosts. Here, we cloned tilapia MC4R, MRAP2b, AgRPs (AgRP, AgRP2), and POMCs (POMCa1, POMCb) genes and characterized the interaction of tilapia MC4R with MRAP2b, AgRP, ?-MSH, and ACTH in vitro. The results indicate the following. (1) Tilapia MC4R, MRAP2b, AgRPs, and POMCs share high amino acid identity with their mammalian counterparts. (2) Tilapia MRAP2b could interact with MC4R expressed in CHO cells, as demonstrated by Co-IP assay, and thus decrease MC4R constitutive activity and enhance its sensitivity to ACTH1-40. (3) As in mammals, AgRP can function as an inverse agonist and antagonist of MC4R, either in the presence or absence of MRAP2b. These data, together with the co-expression of MC4R, MRAP2b, AgRPs, and POMCs in tilapia hypothalamus, suggest that as in mammals, ACTH/?-MSH, AgRP, and MRAP2 can interact with MC4R to control energy balance and thus play conserved roles in the feeding and growth of teleosts.

SUBMITTER: Liu T

PROVIDER: S-EPMC7582737 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Melanocortin Receptor 4 (MC4R) Signaling System in Nile Tilapia.

Liu Tianqiang T Deng Yue Y Zhang Zheng Z Cao Baolong B Li Jing J Sun Caiyun C Hu Zhixing Z Zhang Jiannan J Li Juan J Wang Yajun Y

International journal of molecular sciences 20200924 19

The melanocortin receptor 4 (MC4R) signaling system consists of MC4R, MC4R ligands [melanocyte-stimulating hormone (MSH), adrenocorticotropin (ACTH), agouti-related protein (AgRP)], and melanocortin-2 receptor accessory protein 2 (MRAP2), and it has been proposed to play important roles in feeding and growth in vertebrates. However, the expression and functionality of this system have not been fully characterized in teleosts. Here, we cloned tilapia MC4R, MRAP2b, AgRPs (A ...[more]

PMID: 32987823

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Project description:BACKGROUND: At present pathogenic mechanisms of cancer cachexia are poorly understood. Previous evidence in animal models implicates the melanocortin-4 receptor gene (MC4R) in the development of cancer cachexia. In humans, MC4R mutations that lead to an impaired receptor function are associated with obesity; in contrast, the most frequent polymorphism (Val103Ile, rs2229616; heterozygote frequency approximately 2%) was shown to be negatively associated with obesity. We tested if cancer patients that are homo-/heterozygous for the Val103Ile polymorphism are more likely to develop cachexia and/or a loss of appetite than non-carriers of the 103Ile-allele. METHODS: BMI (body mass index in kg/m2) of 509 patients (295 males) with malignant neoplasms was determined; additionally patients were asked about premorbid/pretherapeutical changes of appetite and weight loss. Cachexia was defined as a weight loss of at least 5% prior to initiation of therapy; to fulfil this criterion this weight loss had to occur independently of other plausible reasons; in single cases weight loss was the initial reason for seeing a physician. The average age in years (+/- SD) was 59.0 +/- 14.5 (males: 58.8 +/- 14.0, females 59.2 +/- 14.0). Blood samples were taken for genotyping of the Val103Ile by PCR- RFLP. RESULTS: Most of the patients suffered from lymphoma, leukaemia and gastrointestinal tumours. 107 of the patients (21%) fulfilled our criteria for cancer cachexia. We did not detect association between the Val103Ile polymorphism and cancer cachexia. However, if we exploratively excluded the patients with early leucaemic stages, we detected a trend towards the opposite effect (p < 0.05); heterozygotes for the 103Ile-allele developed cancer cachexia less frequently in comparison to the rest of the study group. Changes of appetite were not associated with the 103Ile-allele carrier status (p > 0.39). CONCLUSION: Heterozygotes for the 103Ile-allele are not more prone to develop cancer cachexia than patients without this allele; possibly, Ile103 carriers might be more resistant to cancer cachexia in patients with solid tumors. Further studies of the melanocortinergic system in cachexia of patients with solid tumors are warranted.

Dataset Information

Melanocortin Receptor 4 (MC4R) Signaling System in Nile Tilapia.

Publications

Melanocortin Receptor 4 (MC4R) Signaling System in Nile Tilapia.

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