Impaired central leptin signaling and sensitivity in rainbow trout with high muscle adiposity.

The hormone leptin has been identified in all vertebrate classes, but its physiological roles in non-mammalian vertebrates are not well defined. To elucidate leptin regulation in energy homeostasis in a teleost fish species, this study compares hypothalamic and pituitary leptin signaling systems in energetically divergent rainbow trout lines selected for low (lean line, LL) and high (fat line, FL) muscle adiposity under feeding and starvation conditions. In fed fish, hypothalamic gene expression and protein density of the full-functional leptin receptor (LepRL), as well as a leptin binding protein (LepBP) expression, are lower in FL than LL fish. The FL fish have also lower activation of leptin-relevant signaling pathways involving protein kinase B (Akt) and extracellular signal-related kinase. These observations suggests impaired central leptin action in FL fish. During fasting, hypothalamic LepRL and LepBP expression, as well as active Akt levels are downregulated after one week, while pituitary LepRL expression is upregulated, in the LL fish only. After four weeks, hypothalamic LepRL protein levels return to normal levels in both fish lines and Akt is reactivated, although not to the same extent in FL as in LL fish, indicating that FL fish have low leptin sensitivity to nutritional changes. Neuropeptide Y and orexin expression is downregulated to similar levels in both fish lines after one-week fasting. The divergent leptin system profiles between the two fish lines demonstrate that phenotypic selection for high muscle adiposity affects leptin endocrinology, indicating regulatory roles for leptin in rainbow trout energy homeostasis.