PMID- 32208000 OWN - NLM STAT- MEDLINE DCOM- 20200729 LR - 20200729 IS - 1522-1555 (Electronic) IS - 0193-1849 (Linking) VI - 318 IP - 5 DP - 2020 May 1 TI - A translation repressor, 4E-BP1, regulates the triglyceride level in rat liver during protein deprivation. PG - E636-E645 LID - 10.1152/ajpendo.00464.2019 [doi] AB - Protein deprivation has been shown to induce fatty liver in humans and animals, but the molecular mechanisms underlying such induction are largely unknown. Our previous studies have shown that a low-protein diet increases eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) protein and triglyceride (TG) levels in rat liver. 4E-BP1 is known to repress translation by binding to eIF4E. There is also evidence indicating that 4E-BP1 regulates lipid metabolism. Here, we examined the role of 4E-BP1 on TG accumulation in the livers of rats under protein deprivation. The low-protein diet rapidly increased the hepatic 4E-BP1 mRNA level within 1 day, followed by the induction of hepatic TG accumulation. The knockdown of hepatic 4E-BP1 attenuated the TG accumulation in rat liver induced by the low-protein diet. 4E-BP1 knockdown also increased the protein level of carnitine palmitoyltransferase 1A (CPT1A), a regulator of fatty acid oxidation, in the liver of rats fed a low-protein diet. These results indicate that a low-protein diet increases the amount of 4E-BP1, leading to TG accumulation in rat liver. We thus conclude that 4E-BP1 plays an important role in inducing hepatic steatosis under protein deprivation. FAU - Toyoshima, Yuka AU - Toyoshima Y AD - Department of Bioregulation, Institute for Advanced Medical Sciences, Nippon Medical School, Kawasaki, Kanagawa, Japan. FAU - Yoshizawa, Fumiaki AU - Yoshizawa F AD - Department of Agrobiology and Bioresources, School of Agriculture, Utsunomiya University, Utsunomiya, Tochigi, Japan. FAU - Tokita, Reiko AU - Tokita R AD - Department of Bioregulation, Institute for Advanced Medical Sciences, Nippon Medical School, Kawasaki, Kanagawa, Japan. FAU - Taguchi, Yusuke AU - Taguchi Y AD - Department of Bioregulation, Institute for Advanced Medical Sciences, Nippon Medical School, Kawasaki, Kanagawa, Japan. FAU - Takahashi, Shin-Ichiro AU - Takahashi SI AD - Department of Animal Sciences, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo, Japan. FAU - Kato, Hisanori AU - Kato H AD - Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan. FAU - Minami, Shiro AU - Minami S AD - Department of Bioregulation, Institute for Advanced Medical Sciences, Nippon Medical School, Kawasaki, Kanagawa, Japan. LA - eng SI - figshare/10.6084/m9.figshare.11925414.v1 SI - figshare/10.6084/m9.figshare.11955315.v1 PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200324 PL - United States TA - Am J Physiol Endocrinol Metab JT - American journal of physiology. Endocrinology and metabolism JID - 100901226 RN - 0 (Eif4ebp1 protein, rat) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Triglycerides) RN - EC 2.3.1.21 (Carnitine O-Palmitoyltransferase) RN - EC 2.3.1.21 (carnitine palmitoyltransferase-1a, rat) SB - IM MH - Animals MH - Carnitine O-Palmitoyltransferase/metabolism MH - *Diet, Protein-Restricted MH - Gene Knockdown Techniques MH - Intracellular Signaling Peptides and Proteins/genetics/*metabolism MH - Liver/*metabolism MH - Male MH - Rats MH - Rats, Wistar MH - Triglycerides/*metabolism OTO - NOTNLM OT - 4E-BP1 OT - liver OT - low-protein diet OT - rat OT - triglyceride EDAT- 2020/03/26 06:00 MHDA- 2020/07/30 06:00 CRDT- 2020/03/26 06:00 PHST- 2020/03/26 06:00 [pubmed] PHST- 2020/07/30 06:00 [medline] PHST- 2020/03/26 06:00 [entrez] AID - 10.1152/ajpendo.00464.2019 [doi] PST - ppublish SO - Am J Physiol Endocrinol Metab. 2020 May 1;318(5):E636-E645. doi: 10.1152/ajpendo.00464.2019. Epub 2020 Mar 24.