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Hatanaka, A.

Publications and source records attributed to Hatanaka, A..

2 recordsLinked to original sources

A high fat containing chicken egg-only diet suppresses fatty liver induced by a lipid-rich methionine and choline deficient diet.

Nonalcoholic fatty liver disease (NAFLD) is a simple hepatic steatosis, which may proceed to nonalcoholic steatohepatitis (NASH) in the presence of steatosis and inflammation with hepatocyte injury. Obesity induced by a high-fat diet or high monosaccharide diet is considered a risk factor for NAFLD. A popular mouse model of NAFLD is a high-fat diet consisting of 60% energy from fat. A modified methionine and choline deficient (MCD) diet containing 60% energy from fat (CDAHFD) is a quick induction model for NAFLD. Chicken eggs also contain 60% energy from fat with very low carbohydrate. Here we compared liver pathologies in mice fed either a CDAHFD or egg-only diet. We found that a CDAHFD induced NAFLD within only two weeks.Ballooning of hepatocytes with an of immune cell appearance in the liver and high serum ALT and AST indicated that the mice fed CDAHFD developed NAFLD, which could proceed to NASH. However, mice fed an egg-only diet did not develop NAFLD even after 7 weeks. These mice showed normal liver histology with normal ALT and AST. The mice fed an egg-only diet showed high blood ketone bodies and normal blood glucose. Furthermore we found that the mice fed a combination CDAHFD /egg diet or mice fed an egg-only diet after two weeks of CDAHFD diet showed almost normal ALT and AST with reduced levels of fat bodies in the liver. These results indicate that an egg-only diet strongly inhibits high fat and carbohydrates induced NAFLD.Competing Interest StatementThe authors have declared no competing interest.View Full Text

pathology↗

NRF1 and NRF3 complementarily maintain a basal proteasome activity in cancer cells through CPEB3-mediated translational repression

Proteasomes are protease complexes essential for cellular homeostasis, and their activity is crucial for cancer cell growth. However, the mechanism of how proteasome activity is maintained in cancer cells has remained unclear. The CNC family transcription factor NRF1 induces the expression of almost all proteasome-related genes under proteasome inhibition. NRF1 and its phylogenetically closest homolog NRF3 are both highly expressed in several types of cancers, such as colorectal cancer. Herein, we demonstrate that NRF1 and NRF3 complementarily maintain basal proteasome activity in cancer cells. A double knockdown of NRF1 and NRF3 impaired the basal proteasome activity in cancer cells and the cancer cell resistance to a proteasome inhibitor anticancer drug bortezomib by significantly reducing basal expression of seven proteasome-related genes, including PSMB3, PSMB7, PSMC2, PSMD3, PSMG2, PSMG3, and POMP. Interestingly, the molecular basis behind these cellular consequences was that NRF3 repressed NRF1 translation by the gene induction of translational regulator CPEB3, which binds to NRF1-3'UTR and decreases polysome formation on NRF1 mRNA. Consistent results were obtained from clinical analysis, wherein patients with cancer having higher CPEB3/NRF3-expressing tumors exhibit poor prognosis. These results provide the novel regulatory mechanism of basal proteasome activity in cancer cells through an NRF3-CPEB3-NRF1 translational repression axis.

molecular biology↗