- 著者
- Tomoyo Ikeda Tokiro Ishikawa Satoshi Ninagawa Tetsuya Okada Masaya Ono Kazutoshi Mori
- 出版者
- Japan Society for Cell Biology
- 雑誌
- Cell Structure and Function (ISSN:03867196)
- 巻号頁・発行日
- vol.48, no.2, pp.123-133, 2023 (Released:2023-07-19)
- 参考文献数
- 49
When medaka fish (Oryzias latipes) larvae are grown in the absence of exogenous nutrition, the liver becomes dark and positive to Oil Red O staining from 7 days post-hatch (dph). We determined the mechanism of this starvation-induced development of fatty liver by proteomic analysis using livers obtained from larvae grown in the presence or absence of 2% glucose at 5 dph. Results showed that changes in the expression levels of enzymes involved in glycolysis or the tricarboxylic acid cycle were modest, whereas the expression levels of enzymes involved in amino acid catabolism or β-oxidation of fatty acids were significantly elevated, suggesting that they become major energy sources under starvation conditions. Expression levels of enzymes for the uptake and β-oxidation of fatty acids as well as synthesis of triacylglycerol were elevated, whereas those for the synthesis of cholesterol as well as export of cholesterol and triacylglycerol were decreased under starvation conditions, which explains the accumulation of triacylglycerol in the liver. Our results provide the basis for future research to understand how gene malfunction(s) affects the development of fatty liver, which can lead to nonalcoholic steatohepatitis and then to liver cirrhosis.Key words: amino acid catabolism, β-oxidation, triacylglycerol, cholesterol, export
- 著者
- Riwa Ozasa Tetsuya Okada Satomi Nadanaka Takahiko Nagamine Alisha Zyryanova Heather Harding David Ron Kazutoshi Mori
- 出版者
- 日本細胞生物学会
- 雑誌
- Cell Structure and Function (ISSN:03867196)
- 巻号頁・発行日
- vol.38, no.2, pp.183-195, 2013 (Released:2013-08-08)
- 参考文献数
- 39
- 被引用文献数
- 6 30
Patients with schizophrenia receive medication to alleviate various symptoms, but some efficacious second generation antipsychotics, particularly olanzapine, can cause obesity, dyslipidemia, and diabetes mellitus. It has been generally considered that olanzapine contributes to the development of diabetes by inducing obesity and subsequent insulin resistance. In this study, we examined the effect of olanzapine and risperidone, another second generation antipsychotic, on a hamster pancreatic β cell line, and found that both evoked mild endoplasmic reticulum (ER) stress, as evidenced by mild activation of the ER stress sensor molecule PERK. Surprisingly, only olanzapine induced marked apoptosis. Phosphorylation of the α subunit of eukaryotic initiation factor 2, an event immediately downstream of PERK activation, was not observed in cells treated with olanzapine, protein synthesis continued despite PERK activation, and ER stress was thereby sustained. Secretion of insulin was markedly inhibited, and both proinsulin and insulin accumulated inside olanzapine-treated cells. Inhibition of protein synthesis and knockdown of insulin mRNA, which result in less unfolded protein burden, both attenuated subsequent olanzapine-induced apoptosis. Given clinical observations that some patients taking olanzapine exhibit hyperlipidemia and hyperglycemia without gaining weight, our observations suggest that damage to pancreatic β cells may contribute to the undesirable metabolic consequences of olanzapine treatment in some cases.