SPEXIN AS A SATIETY FACTOR IN FISH MODEL: INVOLVEMENT OF GROWTH HORMONE/INSULIN-LIKE GROWTH FACTOR AXIS IN INSULIN-INDUCED SPEXIN EXPRESSION AT HEPATIC LEVEL
Ani Ma, Jin Bai, Mulan He and Anderson On Lam Wong *
School of Biological Sciences, The University of Hong Kong, Hong Kong, China.
Spexin (SPX), a neuropeptide with pleiotropic functions, has been identified as a satiety factor in fish models. In our recent study in goldfish, insulin was shown to be a functional link between feeding and SPX expression in the liver and IGF-I receptor (IGF1R) together with insulin receptor (InsR) were both involved in insulin-induced SPX gene expression at hepatic level, suggesting a possible role of the growth hormone (GH)/insulin-like growth factor (IGF) axis in SPX regulation. In this study, food intake in goldfish was found to up-regulate plasma levels of insulin, SPX and GH with parallel rises of GH mRNA in the pituitary and transcript expression of SPX, IGF-I and IGF-II in the liver. In goldfish pituitary cells, insulin treatment could induce GH secretion without notable changes in GH mRNA expression. In goldfish hepatocytes, GH induction could increase SPX, IGF-I and IGF-II gene expression via activation of JAK2/STAT5, MEK1/2/ERK1/2 and PI3K/Akt pathways and these stimulatory effects were blocked by inhibiting InsR and IGF1R activation. Interestingly, parallel treatment with insulin was found to stimulate IGF-I with concurrent inhibition on IGF-II mRNA expression and these differential effects were mediated by PI3K/Akt but not MAPK cascades. Insulin-induced IGF-I gene expression was additive to the corresponding stimulation by GH whereas co-treatment with GH could revert the inhibitory action of insulin on IGF-II transcript. At hepatocyte level, IGF-I and IGF-II were both effective in stimulating SPX mRNA expression mainly through InsR, and to a lesser extent via IGF1R, by functional coupling with P38 MAPK and PI3K/Akt pathways. These results, as a whole, suggest that insulin can induce SPX expression in goldfish liver via indirect action of GH/IGF axis and local production of IGF-I/-II. Since insulin signal triggered by feeding is known to be transient mainly due to the signal termination by glucose homeostasis, the IGF-I/-II expression at hepatic level may play a role in prolonging/maintaining the SPX responses after food intake in fish model.
Key Words: Spexin, Insulin, Growth Hormone, Insulin-like Growth Factor, Goldfish
Ani Ma, Jin Bai, Mulan He and Anderson On Lam Wong *
School of Biological Sciences, The University of Hong Kong, Hong Kong, China.
Spexin (SPX), a neuropeptide with pleiotropic functions, has been identified as a satiety factor in fish models. In our recent study in goldfish, insulin was shown to be a functional link between feeding and SPX expression in the liver and IGF-I receptor (IGF1R) together with insulin receptor (InsR) were both involved in insulin-induced SPX gene expression at hepatic level, suggesting a possible role of the growth hormone (GH)/insulin-like growth factor (IGF) axis in SPX regulation. In this study, food intake in goldfish was found to up-regulate plasma levels of insulin, SPX and GH with parallel rises of GH mRNA in the pituitary and transcript expression of SPX, IGF-I and IGF-II in the liver. In goldfish pituitary cells, insulin treatment could induce GH secretion without notable changes in GH mRNA expression. In goldfish hepatocytes, GH induction could increase SPX, IGF-I and IGF-II gene expression via activation of JAK2/STAT5, MEK1/2/ERK1/2 and PI3K/Akt pathways and these stimulatory effects were blocked by inhibiting InsR and IGF1R activation. Interestingly, parallel treatment with insulin was found to stimulate IGF-I with concurrent inhibition on IGF-II mRNA expression and these differential effects were mediated by PI3K/Akt but not MAPK cascades. Insulin-induced IGF-I gene expression was additive to the corresponding stimulation by GH whereas co-treatment with GH could revert the inhibitory action of insulin on IGF-II transcript. At hepatocyte level, IGF-I and IGF-II were both effective in stimulating SPX mRNA expression mainly through InsR, and to a lesser extent via IGF1R, by functional coupling with P38 MAPK and PI3K/Akt pathways. These results, as a whole, suggest that insulin can induce SPX expression in goldfish liver via indirect action of GH/IGF axis and local production of IGF-I/-II. Since insulin signal triggered by feeding is known to be transient mainly due to the signal termination by glucose homeostasis, the IGF-I/-II expression at hepatic level may play a role in prolonging/maintaining the SPX responses after food intake in fish model.
Key Words: Spexin, Insulin, Growth Hormone, Insulin-like Growth Factor, Goldfish