Teleost leptins
Leptin | |||||||||||
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Teleost leptins are a family of
. The teleost and mammalian leptins appear to have similar functions, namely, regulation of energy intake and expenditure.The leptin (LEP) hormone was long thought to be specific to mammals, but in recent years the gene (lep) has been found in amphibia such as the tiger salamander (Ambystoma tigrinum),[2][3] and the African clawed frog (Xenopus laevi).[4] The discovery of lep in puffer fish (Takifugu rubripes)[5] demonstrates the ancient ancestry of this hormone.
Examples
There are two closely related lep
Comparison with mammalian leptin
The large differences among endothermic (warm-blooded) mammalian and ectothermic (cold-blooded) teleost leptins raised the question of whether the energy homeostatic functions of the teleost leptins are conserved. Initial phylogenetic analysis has revealed that amino acid conservation with other vertebrate Lep orthologues is low, with only 13.2% sequence identity between torafugu and human LEP.[5] Subsequent investigations have confirmed the low amino acid identity of teleost leps compared to mammalian LEP.[5][10][15][16]
Structure
The three-dimensional homology modeling predicts strong conservation of the tertiary structure between Atlantic salmon and other teleost Leps compared to their mammalian orthologues (Fig. 2).[5][6][7][11][12]
Both lepa1 and lepa2 have two characteristic
The importance of the conserved
Rønnestad and colleagues[6] recently detected five isoforms of the leptin receptor (lepr) that have differences in 3'-end of the mRNA sequence. Of these, only the longest form conserved all functionally important domains (such as three fibronectin type III domains, the Ig C2-like domain, a pair of WSXWS motifs, two JAK2-binding motif boxes, and a STAT-binding domain),[6] while the other four forms have only the intra-cellular region. The long form of mammalian LepR has a function for full signal transduction through the JAK/STAT pathways, whereas the shorter forms exhibit partial or no signaling capabilities.[27][28] The biological importance of long form LepR via the JAK/STAT pathway in maintaining body weight and energy homeostasis has been demonstrated.[29] Previous studies in teleosts have only identified a single lepr.[11][15][30] Rønnestad et al.,[6] is the first to report that plural LepR transcripts in any ectotherm species. When looking at the available motif for lepr, the model suggests that it would bind easily to lepa1 and not lepa2 (Fig. 2). Furthermore, the relatively ubiquitous expression of lepr in salmon tissues supports diverse roles of lep in teleosts.[6]
Tissue distribution
The study on torafugu[5] indicated that lep is mainly expressed in the liver in contrasts to the adipose secretion in mammals.[31][32] However recent studies have shown that lep is expressed in several peripheral tissues, including intestine, kidney, ovary, muscle and adipose tissue.[6][7][11] The multiplicity of lep genes and their low conservation in Teleostei.[10][11][12] suggest that their physiological roles may be more divergent than reported for mammals.
The tissue expression pattern for the Atlantic salmon lep paralogues differs substantially (Fig.3)[6] and hence indicates a possible difference in function. With the exception of the results presented here, and those for zebrafish and Japanese medaka.[6][11][12] Few studies have investigated the broad tissue distribution of lep in teleost fishes. The more distantly related lep genes (lepa and lepb) showed distinct differences in tissue distribution, as shown in e.g. medaka, where lepa is being expressed in liver and muscle, while lepb is more highly expressed in the brain and eye. However, these differences are also observed for more closely related lep paralogues, such as lepa1 in Atlantic salmon, being more highly expressed in brain, liver and white muscle, while lepa2 is mainly expressed in the stomach and midgut. (Fig. 3).
Effects of nutritional status
The observations that long-term feed restriction does not significantly affect lep expression in Atlantic salmon
Short-term feed restriction
Recent studies on short-term effects of a meal or the absence of a meal[18] has revealed that lepa1 expression specifically peaks in the peripheral tissues after 6 – 9 hr in the unfed fish. This suggests that the transcript specific response could be associated with the absence of food. Conversely, since the unfed fish had not received food for 33 hr (24 + 9 hr), the peaks could represent an unrelated effect. Each lepa1 peak occurred during a phase of falling plasma Lep, and since this occurred in both fed and unfed fish, the temporal upregulation of lepa1 does not in fact appear to be specifically related to the absence of food.
The earliest peak of lepa1 occurred in the white muscle, which represents an important lipid reservoir in Atlantic salmon.[34] Unlike pufferfish, which utilizes the liver as a major lipid repository,[5] Atlantic salmon shows that despite a high visceral lipid content, hepatocytes contain few lipid droplets compared to other fish species,[35] yet are an important site for leptin expression.[5][6][7][10][12][18] Moen and colleagues[18] reported that both lepa1 and lepa2 peaked at 9 hr in the liver of unfed fish. By contrast, however, studies in common carp demonstrated a peak in leptin-I(lepa1) and leptin–II (lepa2) in liver at 3 and 6 hr post feeding respectively.[10] The earlier expression response of leptins in common carp likely reflects the higher temperature under which the experiments were conducted, but contrasts the findings of upregulation of lepa1 due to the absence of food.[18] Similarly, in mice, a postprandial increase in hepatic leptin expression has also been reported.[36] However, in grass carp, intraperitoneal injection of recombinant leptin only alters the appetite on the first day, and does not influence food intake during the ensuing 12 days.[16] At present, the data for Atlantic salmon are therefore quite different and suggest that leptin expression in this species may have a complex lipostatic function.
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