The Neuroendocrine Regulation of Food Intake in Fish: A Review of Current Knowledge

Whole-genome duplication (WGD) events have shaped the history of many evolutionary lineages. One such duplication has been implicated in the evolution of teleost fishes, by far the most species-rich vertebrate clade. After initial controversy, there is now solid evidence that such event took place in the common ancestor of all extant teleosts. It is termed teleost-specific (TS) WGD. After WGD, duplicate genes have different fates. The most likely outcome is non-functionalization of one duplicate gene due to the lack of selective constraint on preserving both. Mechanisms that act on preservation of duplicates are subfunctionalization (partitioning of ancestral gene functions on the duplicates), neofunctionalization (assigning a novel function to one of the duplicates) and dosage selection (preserving genes to maintain dosage balance between interconnected components). Since the frequency of these mechanisms is influenced by the genes' properties, there are over-retained classes of genes, such as highly expressed ones and genes involved in neural function. The consequences of the TS-WGD, especially its impact on the massive radiation of teleosts, have been matter of controversial debate. It is evident that gene duplications are crucial for generating complexity and that WGDs provide large amounts of raw material for evolutionary adaptation and innovation. However, it is less clear whether the TS-WGD is directly linked to the evolutionary success of teleosts and their radiation. Recent studies let us conclude that TS-WGD has been important in generating teleost complexity, but that more recent ecological adaptations only marginally related to TS-WGD might have even contributed more to diversification. It is likely, however, that TS-WGD provided teleosts with diversification potential that can become effective much later, such as during phases of environmental change.

A novel neuropeptide which stimulates adenylate cyclase in rat anterior pituitary cell cultures was isolated from ovine hypothalamic tissues. Its amino acid sequence was revealed as: His-Ser-Asp-Gly-Ile-Phe-Thr-Asp-Ser-Tyr-Ser-Arg-Tyr-Arg-Lys-Gln- Met-Ala- Val-Lys-Lys-Tyr-Leu-Ala-Ala-Val-Leu-Gly-Lys-Arg-Tyr-Lys-Gln-Arg-Val-Lys-Asn-Lys - NH2. The N-terminal sequence shows 68% homology with vasoactive intestinal polypeptide (VIP) but its adenylate cyclase stimulating activity was at least 1000 times greater than that of VIP. It increased release of growth hormone (GH), prolactin (PRL), corticotropin (ACTH) and luteinizing hormone (LH) from superfused rat pituitary cells at as small a dose as 10(-10)M (GH, PRL, ACTH) or 10(-9)M (LH). Whether these hypophysiotropic effects are the primary actions of the peptide or what physiological action in the pituitary is linked with the stimulation of adenylate cyclase by this peptide remains to be determined.

The results presented herein demonstrate that apelin is expressed and secreted by both human and mouse adipocytes. Apelin mRNA levels in isolated adipocytes are close to other cell types present in white adipose tissue or other organs known to express apelin such as kidney, heart, and to a lesser extent brown adipose tissue. Apelin expression is increased during adipocyte differentiation stage. A comparison of four different models of obesity in mice showed a large increase in both apelin expression in fat cells and apelin plasma levels in all the hyperinsulinemia-associated obesities and clearly demonstrated that obesity or high-fat feeding are not the main determinants of the rise of apelin expression. The lack of insulin in streptozotocin-treated mice is associated with a decreased expression of apelin in adipocytes. Furthermore, apelin expression in fat cells is strongly inhibited by fasting and recovered after refeeding, in a similar way to insulin. A direct regulation of apelin expression by insulin is observed in both human and mouse adipocytes and clearly associated with the stimulation of phosphatidylinositol 3-kinase, protein kinase C, and MAPK. These data provide evidence that insulin exerts a direct control on apelin gene expression in adipocytes. In obese patients, both plasma apelin and insulin levels were significantly higher, suggesting that the regulation of apelin by insulin could influence blood concentrations of apelin. The present work identifies apelin as a novel adipocyte endocrine secretion and focuses on its potential link with obesity-associated variations of insulin sensitivity status.