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This study aimed to investigate the causal relationship between chronic ingestion of a high-fat diet (HFD)-induced secretion of glucocorticoids (GCs) and the development of non-alcoholic fatty liver disease (NAFLD). We have produced a strain of transgenic mice (termed L/L mice) that have normal levels of circulating corticosterone (CORT), the major type of GCs in rodents, but unlike wild-type (WT) mice, their circulating CORT was not affected by HFD. Compared to WT mice, 12-week HFD-induced fatty liver was less pronounced with higher plasma levels of triglycerides in L/L mice. These changes were reversed by CORT supplement to L/L mice. By analyzing a sort of lipid metabolism-related proteins, we found that expressions of the hepatic cluster of differentiation 36 (CD36) were upregulated by HFD-induced CORT and involved in CORT-mediated fatty liver.Dexamethasone, an agonist of the glucocorticoid receptor (GR), upregulated expressions of CD36 in HepG2 hepatocytes and facilitated lipid accumulation in 109-2811-B-006-520, MOST 107-2320-B-006-054-MY3 and MOST 107-2321-B-001-034 the cells. In conclusion, the fat ingestion-induced release of CORT contributes to NAFLD. This study highlights the pathogenic role of CORT-mediated upregulation of hepatic CD 36 in diet-induced NAFLD.

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Zebrafish is a popular research model; but its mechanism of sex determination is unclear and the sex of juvenile fish cannot be distinguished. To obtain fish with defined sex, we crossed domesticated zebrafish with the Nadia strain that has a female-dominant W segment. These fish were placed on a ziwi:GFP background to facilitate sorting of fluorescent germ cells for transcriptomic analysis. We analyzed the transcriptomes of germ cells at 10–14 days postfertilization (dpf), when sex dimorphic changes started to appear. Gene ontology showed that genes upregulated in the 10-dpf presumptive females are involved in cell cycles. This correlates with our detection of increased germ cell numbers and proliferation. We also detected upregulation of meiotic genes in the presumptive females at 14 dpf. Disruption of a meiotic gene, sycp3, resulted in sex reversal to infertile males. The germ cells of sycp3 mutants could not reach diplotene and underwent apoptosis. Preventing apoptosis by disrupting tp53 restored female characteristics in sycp3 mutants, demonstrating that adequate germ cells are required for female development. Thus, our transcriptome and gene mutation demonstrate that initial germ cell proliferation followed by meiosis is the hallmark of female differentiation in zebrafish.