Role for leptin in promoting glucose mobilization during acute hyperosmotic stress in teleost fishes

Abstract

Osmoregulation is critical for survival in all vertebrates, yet the endocrine regulation of this metabolically expensive process is not fully understood. Specifically, the function of leptin in the regulation of energy expenditure in fishes, and among ectotherms, in general, remains unresolved. In this study, we examined the effects of acute salinity transfer (72 h) and the effects of leptin and cortisol on plasma metabolites and hepatic energy reserves in the euryhaline fish, the tilapia (Oreochromis mossambicus). Transfer to 2/3 seawater (23 ppt) significantly increased plasma glucose, amino acid, and lactate levels relative to those in the control fish. Plasma glucose levels were positively correlated with amino acid levels (R 2 Z0.614), but not with lactate levels. The mRNA expression of liver leptin A (lepa), leptin receptor (lepr), and hormone-sensitive and lipoprotein lipases (hsl and lpl) as well as triglyceride content increased during salinity transfer, but plasma free fatty acid and triglyceride levels remained unchanged. Both leptin and cortisol significantly increased plasma glucose levels in vivo, but only leptin decreased liver glycogen levels. Leptin decreased the expression of liver hsl and lpl mRNAs, whereas cortisol significantly increased the expression of these lipases. These findings suggest that hepatic glucose mobilization into the blood following an acute salinity challenge involves both glycogenolysis, induced by leptin, and subsequent gluconeogenesis of free amino acids. This is the first study to report that teleost leptin A has actions that are functionally distinct from those described in mammals acting as a potent hyperglycemic factor during osmotic stress, possibly in synergism with cortisol. These results suggest that the function of leptin may have diverged during the evolution of vertebrates, possibly reflecting differences in metabolic regulation between poikilotherms and homeotherms.

Chronic cortisol and the regulation of food intake and the endocrine growth axis in rainbow trout

“…The reduction in liver and muscle lipid content in the cortisol-treated fish is consistent with the increased lypolytic capacity of chronically stressed fish (Mommsen et al 1999). Cortisol may deplete lipid reverses in fish by increasing the activity of various lipases (Sheridan 1986, Baltzegar et al 2014) and glycerol utilization (Vijayan et al 1991), and by reducing the lipogenic potential of the liver (Vijayan et al 1990, Laiz-Carrió n et al 2003, Ló pez-Patino et al 2014. Moreover, given the known lipolytic properties of GH in the liver (Björnsson et al 2002), our results suggest that cortisol may also promote lipolysis via its stimulatory effects on liver ghr2 expression.…”

“…Previous studies in fish have shown that cortisol exposure can increase, decrease, or have no effect on liver glycogen content and there is generally no consensus as to the role of cortisol in liver glycogen metabolism (Mommsen et al 1999, De Boeck et al 2001, Laiz-Carrió n et al 2003. In tilapia (O. mossambicus), while injections of both cortisol and leptin increase plasma glucose levels, only leptin decreases liver glycogen content (Baltzegar et al 2014). Given our observation that cortisol stimulates leptin gene expression, an interesting avenue for future research will be to determine whether the glycolytic effects of cortisol in rainbow trout are indirect and mediated by leptin.…”

Leptin signaling regulates glucose homeostasis, but not adipostasis, in the zebrafish

“…The leptin receptordeficient diabetes (db/db) mouse exhibits hyperglycemia by 3-4 wk of age (19). Hepatic mRNA levels for leptin have been shown to change upon fasting in zebrafish, common carp, Atlantic salmon, and Arctic charr (5), and recombinant leptin was shown to induce hepatic glucose mobilization in tilapia (20). Thus, we next sought to examine effects of leptin receptor deficiency on glucose homeostasis in the zebrafish (Fig.…”

Hypoxemia-induced leptin secretion: a mechanism for the control of food intake in diseased fish

“…Similarly, given the important roles of leptin in the regulation of hematopoiesis (Bennett et al 1996), angiogenesis (Anagnostoulis et al 2008), and the immune system (Carlton et al 2012, Mariano et al 2013), a promising avenue for future research in C. salmositicaand T. borreli-infected fish may be to explore the contribution of leptin to the regeneration of hematopoietic tissues during the chronic stage of infection and its effects on the innate and acquired immune responses that characterize these diseases (Woo & Ardelli 2014). Recent studies in fish have shown that leptin can function as a hyperglycemic factor (Baltzegar et al 2014) and stimulate metabolic rate (Dalman et al 2013). Therefore, given the considerable bioenergetic cost of C. salmositica infection (Beamish et al 1996, Woo 2003, leptin may also play an important role in regulating energy expenditure or promoting catabolic processes during the sustained phase of infection.…”