Nutrient Sensing in Atlantic Salmon ‐ Exploring the Sensory Systems for Amino Acids in the Gastrointestinal Tract

Abstract

Over the last years there has been an improved understanding of the underlying mechanisms involved in nutrient sensing, and how the gastrointestinal tract (GIT) conveys information on ingested food to the brain and other organs. In mammals, several receptors from the G protein‐coupled receptors (GPCRs) superfamily have been identified as nutrient sensors that respond to organic nutrients or their breakdown products, i.e. fatty acids, sugars, amino acids (AAs) and proteolytic products. The AAs and peptides sensory mechanisms in the GIT are involved in modulating pancreatic exocrine and endocrine secretions as well as protein digestion in order to optimize nutrient utilization and control feed intake. While it is well acknowledged that the nutrient sensing system is a key player in the control of these functions in mammals, almost no information exist in teleosts, the largest vertebrate group with more than 25000 species. In Atlantic salmon (Salmo salar), a key commercial species in global aquaculture, it is of high interest to understand how specific AA enhance feed intake, growth and fish quality. In addition, Atlantic salmon has undergone an additional and relatively recent whole‐genome duplication event, the salmonid‐specific 4th WGD. Atlantic salmon therefore represent an excellent model system to study the role of gene duplication and adaptation.Key mammalian GPCRs involved in AA and peptide sensing in GIT belong to GPCR family C and A, respectively. The lysophosphatidic acid receptor 5 (LPAR5) belongs to family A and is responsive to peptides. The family C consists of members such as the metabotropic glutamate receptors (mGluRs), calcium‐sensing receptor (CasR), GPCR family C subtype 6A (GPRC6A) and taste receptors (T1Rs). Whereas the mGluRs are monogamous for L‐Glu, the CasR, GPR6A and T1Rs are promiscuous by nature and respond to, e.g., subsets of L‐α‐AAs and divalent cations. Such promiscuity for nutrients by the receptors in relevant tissues allows for a specific nutrient‐sensing capacity of emerging physiological significance.Our study is based on the hypothesis that the nutrient sensing system is conserved throughout vertebrate phylogeny. Based on this hypothesis, we have analyzed the presence of these receptors in the salmon genome. Homologues of vertebrate LPA5R gene were identified in silico and validated by cDNA cloning and sequencing. The salmon LPAR5 shared more than 50% AA sequence similarity with other vertebrate homologues. Members of GPCR family C were also identified in the salmon genome: five T1R1 transcripts, two T1R3, six GPR6A, thirteen mGluR1, seven mGluR4 and three CaSR transcripts. We have now started to validate the different transcript sequences by RT‐PCR amplification and cloning. Sequence comparative analysis indicates that 7 transmembrane domains and sequence motifs of the predicted salmon GPCRs family C are generally maintained across vertebrates. The remarkable conservation of primary sequences within vertebrates supports our hypothesis. This information is fundamental for further comparative studies and to study receptors pharmacology and biological responses in salmon.Support or Funding InformationSupported by RFFVEST (project no. 247978) and University of Bergen