Characteriztion of a leptin receptor paralog and its response to fasting in rainbow trout(Oncorhynchus mykiss)

Authors: Mankiewicz, Jamie; Cleveland, Beth

Submitted to: International Journal of Molecular Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/16/2021
Publication Date: 7/20/2021
Citation: Mankiewicz, J.L., Cleveland, B.M. 2021. Characteriztion of a leptin receptor paralog and its response to fasting in rainbow trout(Oncorhynchus mykiss). International Journal of Molecular Sciences. 22: 7732. https://doi.org/10.3390/ijms22147732.
DOI: https://doi.org/10.3390/ijms22147732

Interpretive Summary: The hormone leptin has been well characterized for its role in regulating appetite, specifically inhibiting food intake in vertebrates. In most fishes there is a single leptin receptor (LepRA1), however, duplicated receptors have recently been documented in a few species. Here we revealed a second leptin receptor (LepRA2) in rainbow trout. Evolutionary-based analyses show a salmonid specific genome duplication event 25-100 million years ago as the probable origin of the second leptin receptor, or paralog, appearing in trout and these paralogs showed different tissue-specific expression patterns. We exposed rainbow trout to a two-week period of feed deprivation to evaluate how the receptors respond to conditions where the body is mobilizing energy stores. The data show that the two leptin receptor paralogs identified in rainbow trout appear to have unique functions as they are differentially expressed across tissues and under fasted conditions. As we gain understanding about leptin and its receptors in fishes and other ectotherms, the wide-ranging actions of this hormone becomes more apparent. While regulating appetite is a notable function of leptin, it is clear that through the tissue-specific actions of its receptors the hormone can impact many other aspects of life history in fishes.

Technical Abstract: Leptin is a cytokine that regulates appetite and energy expenditure, where in fishes is primarily produced in the liver and acts to mobilize carbohydrates. In most fishes there is one leptin receptor (LepRA1), however, paralogs have been documented in a few species. Here we revealed a second leptin receptor (LepRA2) in rainbow trout that has a 77% amino acid sequence identity to trout LepRA1 and 93% to salmon LepRA2. Phylogenetic analyses show the salmonid specific genome duplication event as the probable origin of the second LepR in trout. A tissue distribution showed tissue specific expression of these receptors, with lepra1 levels highest in the ovaries, nearly 50-fold higher than lepra2. Interestingly, lepra2 mRNA was most highly expressed in the liver while hepatic lepra1 was virtually undetectable. To evaluate the effects of these receptors under catabolic conditions, we exposed rainbow trout to a two-week period of feed deprivation. Body indices declined in the feed restricted group at one and two weeks and plasma leptin was lower in fasted fish at one week. Hepatic lepra2 mRNA increased 1.5-fold by one week and remained elevated at two weeks of fasting, while expression of lepra1 remained low. By contrast, muscle lepra1 increased 2- and 3-fold at one and two weeks of fasting, respectively, while adipose lepra1 was lower in fasted fish. lepra2 transcript levels were not affected in muscle and fat. These data show lepra1 and lepra2 are differentially expressed across tissues and during feed deprivation, suggesting paralog- and tissue-specific functions for these receptors.