Acute anorexigenic action of leptin in rainbow trout is mediated by the hypothalamic Pi3k pathway

Abstract

Leptin (Lep) is an anorexigenic hormone and regulates appetite-related neuropeptides in mammals. A number of neuropeptides have also been linked to appetite regulation in teleost fish, but Lep signaling activation and effects on appetite-regulating neurons are poorly elucidated in early vertebrates. This study uses cellular, tissue and organismal approaches to elucidate the acute, central Lep action in rainbow trout. The results demonstrate that Lep activates phosphorylation of protein kinase B (Akt) and signal transducer and activator of transcription 3 in rainbow trout hypothalamus-derived cells, and that the phosphatidylinositol-3-kinase (Pi3k) inhibitor LY294002 can suppress the Lep-induced Akt phosphorylation. Intracerebroventricular (ICV) Lep administration strongly suppresses food intake at the doses of 0.05 and 0.5 µg Lep fish −1 . At low dose, Lep stimulates hypothalamic transcription of anorexigenic cocaine-and amphetamineregulated transcript (Cart) and orexigenic neuropeptide Y. At high dose, Lep stimulates hypothalamic transcription of anorexigenic proopiomelanocortin (Pomc) A1, A2, and B, while coinjection with LY294002 reverses this upregulation. The data suggest that the anorexigenic action of Lep in rainbow trout is mediated through stimulation of the anorexigenic neuropeptides Pomc and Cart. Furthermore, ICV Lep treatment increases phosphor-Akt-immunoreactive cells in the nucleus lateralis tuberis, periventricular zone along infundibulum, and lateral recess surrounded by nucleus anterior tuberis, while LY294002 inhibits this effect. Lep receptor-immunoreactive cells are also predominant in these regions. These results demonstrate that Lep activates the Pi3k-Akt pathway in the lateral tuberal hypothalamus of rainbow trout for acute appetite regulation, indicating the conservation of anorexigenic Lep action in the mediobasal hypothalamus.

Nutrient Sensing Systems in Fish: Impact on Food Intake Regulation and Energy Homeostasis

“…Leptin treatment is usually anorectic in fish as demonstrated studies in rainbow trout (Murashita et al, 2008; Kling et al, 2009; Aguilar et al, 2010; Gong et al, 2016a), goldfish (Volkoff et al, 2003; de Pedro et al, 2006; Vivas et al, 2011) and striped bass (Won et al, 2012). This anorectic effect occurred in parallel with changes in the expression of neuropeptides generally indicating an enhanced anorexigenic potential.…”

“…Indeed, Librán-Pérez et al (2015b) demonstrated that protein levels of AMPK, Akt, and mTOR increased in hypothalamus of fish fed a lipid-enriched diet. Furthermore, Gong et al (2016a) demonstrated increased Akt protein levels in isolated hypothalamic cells incubated with leptin. Finally, Velasco et al (2016b) also suggested the possible involvement of ceramides in the connection between activation of hypothalamic fatty acid sensing systems, neuropeptide mRNA abundance, and control of food intake.…”

“…Thus, leptin treatment induced a decrease in NPY mRNA levels in hypothalamus of rainbow trout (Murashita et al, 2008; Aguilar et al, 2011), hypothalamus and telencephalon of goldfish (Volkoff et al, 2003), and in whole brain in grass carp (Li et al, 2010). POMC mRNA abundance increased in response to leptin treatment in rainbow trout (Murashita et al, 2008; Aguilar et al, 2011; Gong et al, 2016a). Leptin treatment also increased CART mRNA levels in hypothalamus of goldfish (Volkoff and Peter, 2001), catfish (Subhedar et al, 2011), and rainbow trout (Murashita et al, 2008; Aguilar et al, 2011; Gong et al, 2016a).…”

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

“…In goldfish, leptin injections decrease feeding and locomotor behavior (Volkoff et al, 2003; de Pedro et al, 2006; Vivas et al, 2011; Tinoco et al, 2012) in part by stimulating anorexigenic sytems (e.g., CART, CCK, and POMC) and inhibiting orexigenic ones (e.g., orexin, NPY, AgRP) (Volkoff et al, 2003; Yan et al, 2016). Similarly, in rainbow trout (Salmoniforme), central leptin administration suppresses food intake and increases the hypothalamic expressions of CART and POMC (Gong et al, 2016). Leptin treatment also inhibits feeding in grass carp (Li et al, 2010) (Cypriniforme) and increases energy expenditure in zebrafish larvae (Renquist et al, 2013).…”

Mechanisms involved in the regulation of neuropeptide-mediated neurite outgrowth: a minireview

“…Recent study has demonstrated that PI3K signaling participates in the regulation of neuropeptide Y-and proopiomelanocortin-mediated appetite suppression (Chu et al 2014). Furthermore, involvement of the PI3K/Akt pathway in the appetite regulation has been suggested in diff erent study (Gong et al 2015). Activation of oxytocin receptor is associated with PI3K and extracellular signalregulated kinase signaling pathways (Lin et al 2012).…”