Agouti-related protein (AgRP) is a neuropeptide synthesized by AgRP/NPY neurons and transcribed as 132 amino acids in humans and 142 amino acids (AgRP1) in Japanese seabass (Lateolabrax maculatus) fish. AgRP neurons are activated by hormonal signals of energy deficits and inhibited by signals of energy surpluses and have been demonstrated to have the ability to sense the dynamics of blood glucose concentrations as the “glucose sensor” in mammals. It is widely recognized that AgRP is an endogenous antagonist of the melanocortin-3 and -4 receptors (MC3R and MC4R) in the hypothalamus, exhibiting potent orexigenic activity and control of energy homeostasis. Most fish, especially carnivorous fish, cannot make efficient use of carbohydrates. When carbohydrates like corn or wheat bran are added as energy sources, they often cause feeding inhibition and metabolic diseases. When fishmeal is replaced by plant protein, this does not completely eliminate carbs, limiting the utilization of carbohydrates and plant proteins in aquaculture. Our previous study showed that AgRP, and not neuropeptide Y (NPY) is the principal protein molecule that correlates well with feeding behavior in Japanese seabass from anorexia to adaptation. The Ghrelin/Leptin-mTOR-S6K1-NPY/AgRP/POMC feed intake regulatory pathway responds to the plant-oriented protein which contains glucose. However, its regulatory function and mechanism are still not clear. This review offers an integrative overview of how glucose signals converge on a molecular level in AgRP neurons of the arcuate nucleus of the hypothalamus. This is in order to control fish food intake and energy homeostasis.
Insulin-like growth factor 1 (IGF1) is an essential effector of the growth hormone (GH)/IGF1 axis for somatic growth regulation in mammals. However, its functions have not been thoroughly investigated in zebrafish in vivo. In this study, the igf1-deficient zebrafish model was developed using the CRISPR/Cas9 technique. In this study all the results were performed on both male and female animals. The growth of both male and female igf1-deficient zebrafish were reduced. The igf1 deficiency leads to significant complementary up-regulation of transcriptional expression levels of insulin, igf2 and igf3. This suggested that igf2 and igf3 may act with redundant functions. While the upregulation of gh1 expression can only be detected in igf1-deficient females. At the same time, significant growth retardation, fatty liver, reduced activated levels of ribosomal S6 (S6) are seen only in igf1-deficient males. On the other hand, significant hyperglycemia, elevated transcriptional expression levels of phosphenolpyruvate carboxykinase (pepck) and levels of phosphorylated extracellular signal-regulated kinase (ERK1/2), with additional reduced hepatic lactate/pyruvate (L/P) ratios can only observed in igf1-deficient females. Impaired glucose uptake has been recorded in the primary cultured hepatocytes from igf1-deficient females, but not males. Intriguingly, exposure to 17beta-estroadiol (E2) can partially ameliorated the defects of fatty liver and activation of AKT/mTOR signaling in igf1-deficient males. Our studies demonstrate the significant functions of IGF1 on somatic regulation in zebrafish, with asymmetric gender-related consequences. Our data thus suggest that the zebrafish IGF1 is preferentially required for the activation of AKT/mTOR signaling in male zebrafish, but glucose uptake in females.