AN INCREASE IN 4E-BP1 LEVEL MEDIATES TO ENHANCE TRIGLYCERIDE ACCUMULATION IN RAT LIVER UNDER PROTEIN MALNUTRITION

Background and objectives: We have shown that feeding of a low-protein diet increases the amount of eukaryotic translation initiation factor (eIF) 4E-binding protein 1 (4E-BP1), a substrate of mammalian target of rapamycin complex 1 (mTORC1) in rat liver. There are increasing evidences that mTORC1 p...

Full description

Saved in:
Bibliographic Details
Published in:Annals of nutrition and metabolism 2017-10, Vol.71 (Suppl. 2), p.440
Main Authors: Toyoshima, Yuka, Tokita, Reiko, Taguchi, Yusuke, Yoshizawa, Fumiaki, Takahashi, Shin-Ichiro, Kato, Hisanori, Minami, Shiro
Format: Article
Language:English
Subjects:
Accumulation
Casein
Diet
Feeding
Initiation factor eIF-4G
Injection
Lipid metabolism
Liver
Low protein diet
Malnutrition
Metabolism
Nutrient deficiency
Proteins
Rapamycin
Rats
Ribonucleic acid
RNA
Rodents
Scaffolding
Substrates
TOR protein
Triglycerides
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Background and objectives: We have shown that feeding of a low-protein diet increases the amount of eukaryotic translation initiation factor (eIF) 4E-binding protein 1 (4E-BP1), a substrate of mammalian target of rapamycin complex 1 (mTORC1) in rat liver. There are increasing evidences that mTORC1 pathway controls lipid metabolism. However, the role of 4E-BP1 in the regulation of lipid metabolism is not clear. The present study was undertaken to examine whether 4E-BP1 is involved in the enhancement of hepatic triglyceride (TG) accumulation in rats fed a low-protein diet. Methods: Experiment 1. In order to increase 4E-BP1 in the liver artificially, five-week-old rats were injected via their tail vein with adenovirus (Ad) expressing rat 4e-bp1 or LacZ and fed a standard chow. Seven days after Ad injection, their livers were collected. Experiment 2. In order to knockdown hepatic 4E-BP1 under protein malnutrition, five-week-old rats were injected via their tail vein with Ad expressing rat 4e-bp1 short-hairpin RNA (sh4EBP1) or non-specific short-hairpin RNA. Eight days after Ad injection, each Ad-injected group was divided into two groups. One was fed a 15% casein diet as a control diet and the other was fed a 5% casein diet (5C) as a low-protein diet for 4 days. On the 5th day, their livers were collected. Results: Experiment 1. The 4E-BP1 overexpression did not change hepatic TG levels. Experiment 2. The 5C-feeding increased 4E-BP1 levels in the liver of both Ad-injected rats, but 4E-BP1 knockdown by sh4EBP1 Ad injection suppressed 5C-feeding-induced increases in hepatic 4E-BP1 levels. The 4E-BP1 knockdown also suppressed 5C-feeding-induced increases in the protein levels of eIF4G, a translation initiation scaffolding protein, in the liver. Hepatic TG levels were significantly increased by 5C-feeding in the liver of both Ad-injected rats. However, 4E-BP1 knockdown attenuated 5C-feeding-induced hepatic TG accumulation. Conclusions: These data indicate that TG accumulation is not enhanced just by increasing 4E-BP1 in the liver, although the increase in 4E-BP1 levels is necessary to enhance TG accumulation in the liver under protein malnutrition. In addition, it is suggested that 4E-BP1 might control TG levels in concert with eIF4G in rat liver under protein malnutrition.
ISSN:0250-6807
1421-9697
DOI:10.1159/000480486