Evidence for a leptin–insulin axis in a fish, the tilapia (Oreochromis mossambicus)

Authors: DECK, COURTNEY - North Carolina State University; Mankiewicz, Jamie; BORSKI, RUSSEL - North Carolina State University; Cleveland, Beth

Submitted to: Journal of Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/14/2022
Publication Date: N/A
Citation: N/A
DOI: https://doi.org/10.1530/JOE-21-0139

Interpretive Summary: Leptin, insulin, and glucagon are involved in regulating glycaemia in vertebrates and play a role in the progression of obesity and type 2 diabetes. While mammals possess an ‘adipoinsular axis’ whereby insulin stimulates leptin release from adipocytes and leptin in turn feeds back on the pancreas to inhibit further insulin secretion, evidence of such an axis in non-mammalian vertebrates is unknown. We investigated the interactions between these glycaemic hormones and provide evidence for a leptin– insulin axis in a teleost fish, the tilapia. In the first study, we exposed hepatocytes to various concentrations of either insulin or glucagon to determi ne effects on leptin a (lepa) and then examined this in vivo with i.p. injections of both hormones. We also exposed isolated Brockmann bodies (pancreatic islets) to recombinant tilapia leptin A (rtLepA) and again followed this up with an i.p. injection to examine changes in insulin a and glucagon b. We found that glucagon increases lepa in vitro and in vivo, with the latter being 18-fold higher than saline-injected controls; however, th e effects of rtLepA on glub were more variable. Insulin increased lepa by 2.5-fold in vitro and 70-fold in vivo, while rtLepA decreased insa at basal and increased it at high glucose concentrations. These data indicate that a leptin–insulin axis may be conserved among vertebrates and is thus essential for regulating nutrient balance but that the relationship is likely much more dynamic in teleosts as glycaemia is not as tightly regulated as it is in mammals.

Technical Abstract: Leptin is a cytokine known to regulate appetite and energy expenditure, where in fishes is primarily produced in the liver and acts to mobilize carbohydrates. In fishes, there is typically one leptin receptor (LepRA1) with truncated versions that can act as binding proteins, however, paralogs have been documented in a few fish including Atlantic salmon. Here we revealed a second leptin receptor (LepRA2) in rainbow trout that has a 76% amino acid sequence identity to trout LepRA1 and 94% to salmon LepRA2. 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 lepra1 is virtually undetectable in this tissue. To evaluate the effects of these receptors under catabolic conditions, we exposed rainbow trout to a two-week period of feed deprivation. Body weight, hepatosomatic and viserosomatic indices, and blood glucose were significantly decreased in the feed restricted group compared to fed controls at one and two weeks. Hepatic lepra2 mRNA increased 0.5-fold by one week and remained elevated at two weeks of fasting, while expression of lepra1 remained low. By contrast, white muscle lepra1 expression increased 3- and 5-fold at one and two weeks of fasting, respectively, however, lepra2 transcript levels were not affected. These data show lepra1 and lepra2 are differentially expressed across tissues and during a fasted catabolic state, suggesting there are paralog- and tissue-specific functions for these receptors.