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

Abstract

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.

Functional Analysis and Tissue-Specific Expression of Calcitonin and CGRP with RAMP-Modulated Receptors CTR and CLR in Chickens

“…The fluorescence activity of the luciferase in each treatment group was measured using a multimode microplate reader (TriStar LB941, Berthold Technologies, Bad Wildbad, Germany). Finally, the fluorescence activity of each treatment group was expressed as a relative increase ratio compared to the control group [35,36].…”

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

“…A recent study shows that chicken MC5R has a higher affinity to ACTH/α-MSH, and is coupled to the cAMP/ protein kinase A (PKA) signaling pathway. As ACTH can promote gluconeogenesis and reduce triglyceride content in primary hepatocytes, it suggests that ACTH/MC5R may have an important role in regulating glucose and lipid metabolism in chicken liver [28].…”

Polymorphisms and expressions of ADSL, MC4R and CAPN1 genes and their effects on economic traits in Egyptian chicken breeds

“…This methodology, which allows for early prognosis and inter-breed comparisons, aids in steering the trajectory of chicken breeding strategies towards more productive outcomes [ 2 , 6 ]. Prominently situated within the pantheon of candidate genes orchestrating quantitative production traits in chickens are melanocortin-4-receptor (MC4R), adenylosuccinate lyase (ADSL), and calpain 1 (CAPN1) genes [ 2 , 17 , 18 ]. The MC4R gene occupies a pivotal role in feeding regulation and energy homeostasis [ 19 ], while concurrently exerting its influence over physiological processes spanning lipolysis, immunology, and adrenal steroidogenesis [ 18 ].…”

“…Prominently situated within the pantheon of candidate genes orchestrating quantitative production traits in chickens are melanocortin-4-receptor (MC4R), adenylosuccinate lyase (ADSL), and calpain 1 (CAPN1) genes [ 2 , 17 , 18 ]. The MC4R gene occupies a pivotal role in feeding regulation and energy homeostasis [ 19 ], while concurrently exerting its influence over physiological processes spanning lipolysis, immunology, and adrenal steroidogenesis [ 18 ]. Studies have elucidated the significant interplay between MC4R gene activity and body weight in chickens, underscoring distinct MC4R genotypes as determinants of protein functions integral to body weight dynamics [ 2 , 13 , 20 , 21 ].…”