AUTHOR=Zeng Ningmei , Bao Jiankang , Shu TingTing , Shi Chuang , Zhai Gang , Jin Xia , He Jiangyan , Lou Qiyong , Yin Zhan 

TITLE=Sexual dimorphic effects of igf1 deficiency on metabolism in zebrafish


JOURNAL=Frontiers in Endocrinology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.879962

DOI=10.3389/fendo.2022.879962

ISSN=1664-2392

ABSTRACT=<p>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 <italic>in vivo</italic>. In this study, the <italic>igf1</italic>-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 <italic>igf1</italic>-deficient zebrafish were reduced. The <italic>igf1</italic> deficiency leads to significant complementary up-regulation of transcriptional expression levels of <italic>insulin, igf2</italic> and <italic>igf3</italic>. This suggested that <italic>igf2</italic> and <italic>igf3</italic> may act with redundant functions. While the upregulation of <italic>gh1</italic> expression can only be detected in <italic>igf1</italic>-deficient females. At the same time, significant growth retardation, fatty liver, reduced activated levels of ribosomal S6 (S6) are seen only in <italic>igf1-</italic>deficient males. On the other hand, significant hyperglycemia, elevated transcriptional expression levels of <italic>phosphenolpyruvate carboxykinase</italic> (<italic>pepck</italic>) and levels of phosphorylated extracellular signal-regulated kinase (ERK1/2), with additional reduced hepatic lactate/pyruvate (L/P) ratios can only observed in <italic>igf1</italic>-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 <italic>igf1</italic>-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.</p>