Characterization of a Leptin Receptor Paralog and Its Response to Fasting in Rainbow Trout (Oncorhynchus mykiss)

Abstract

Leptin is a cytokine that regulates appetite and energy expenditure, where in fishes it is primarily produced in the liver and acts to mobilize carbohydrates. Most fishes have only one leptin receptor (LepR/LepRA1), however, paralogs have recently been documented in a few species. Here we reveal a second leptin receptor (LepRA2) in rainbow trout that is 77% similar to trout LepRA1. Phylogenetic analyses show a salmonid specific genome duplication event as the probable origin of the second LepR in trout. Tissues distributions showed tissue specific expression of these receptors, with lepra1 highest in the ovaries, nearly 50-fold higher than lepra2. Interestingly, lepra2 was most highly expressed in the liver while hepatic lepra1 levels were low. Feed deprivation elicited a decline in plasma leptin, an increase in hepatic lepra2 by one week and remained elevated at two weeks, while liver expression of lepra1 remained low. By contrast, muscle lepra1 mRNA increased at one and two weeks of fasting, while adipose lepra1 was concordantly 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 leptin receptors.

Recent advances in the crosstalk between adipose, muscle and bone tissues in fish

“…The physiological actions of leptin are mediated by a glycoprotein consisting of a single-membrane-spanning receptor (LepR), that belongs to the class-I cytokine receptor family ( 88 ). In fish, an orthologous gene for the mammalian lepr was identified in several species ( 62 ), typically present as a single ortholog; however, duplicate lepr paralogs have been identified in a few species, including Atlantic salmon ( 89 ), European eel ( 71 ) or rainbow trout ( 86 ). Furthermore, in some species more than one isoform is present, as it also occurs in mammals, generated by alternative mRNA splicing and/or proteolytic processing of the protein products ( 88 ).…”

“…Another indirect evidence of leptin actions on fish muscle came from studies on lepr expression, which is modulated by nutritional status. The two lepr paralogs identified in rainbow trout are differentially expressed across tissues under catabolic conditions, showing that during fasting, leptin is likely acting to promote energy mobilization in the muscle through lepra1 and in the liver through lepra2 ( 86 ).…”

“…It is not surprising that leptin, as a regulator of energy expenditure, is controlled at least in part by glucose and key elements of the endocrine stress axis. In this sense, recently, Mankiewicz et al (86), using tilapia (Oreochromis mossambicus) freshly isolated hepatocytes' incubations and a homologous leptin A ELISA, showed that its secretion is modulated by high levels of glucose. In the same study, an in vivo injection of epinephrine stimulated a rapid rise in blood glucose, which was followed by a 4fold increase in hepatic lepA mRNA and plasma levels.…”

Regulatory Subfunctionalization drives OXPHOS evolution in teleosts

“…In contrast, the accumulation of harmful mutations can lead to non-functionalization eliminating the redundant copies. Within the same organism, various tissues and organs may exhibit varying degrees of functional redundancy and divergence across duplicates (Bermejo-Nogales et al, 2015;Gallagher & Macqueen, 2016;Mankiewicz & Cleveland, 2021;Porplycia et al, 2017). In addition, certain duplicated genes have the capacity to carry out redundant tasks throughout development and to switch to different roles in adulthood (Bochkis et al, 2012).…”

Molecular Characterization and Expression Response of Ghrelin, GLP-1 and PYY to Fasting, Dietary Lipid, and Fatty Acids in Silver Pomfret (Pampus argenteus)

“…Fish appetite could be increased by fasting [20] and their nutritional status could be regulated by alternation of the endocrine hormones [21]. The effect of fasting on fish appetite has been reported in Leopard Mandarin fish (Siniperca scherzeri) [22], rainbow trout [23], and Siberian sturgeon (Acipenser baeri) [24]. However, the physiological effects of fasting on the fish gut remain largely unknown.…”