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Protamine-derived peptide RPR (Arg-Pro-Arg) ameliorates oleic acid-induced lipogenesis via the PepT1 pathway in HepG2 cells.

Abstract
The protamine-derived peptide arginine-proline-arginine (RPR) can ameliorate lifestyle-related diseases such as obesity and hypercholesterolemia. Thus, we hypothesized that the hypolipidemic activity of RPR could attenuate events leading to non-alcoholic fatty liver disease. Addition of 2 m m oleic acid (OA) to the culture medium induced fatty liver conditions in HepG2 cells. The OA + RPR group showed significantly decreased cellular or medium triglyceride (TG) level compared with the OA group. Stearoyl-CoA desaturase-1 (SCD1) or sterol regulatory element-binding protein 1 (SREBP1) protein level was significantly lower in the OA + RPR group than in the OA group. In the R + P + R amino acid mixture-treated group, the TG level was not significantly different from that in the OA-treated group. The OA + RP- or OA + PR-treated groups showed significantly decreased cellular TG level compared with the OA group. Moreover, the effect of RPR disappeared when the peptide transporter 1 (PepT1) was knocked down with a siRNA. Collectively, our results demonstrated that RPR effectively ameliorated hepatic steatosis in HepG2 cells via the PepT1 pathway.
AuthorsMaihemuti Mijiti, Ryosuke Mori, Yuga Nakashima, Arata Banno, Yuyang Ye, Asahi Takeuchi, Shoya Matsuba, Keisuke Kiriyama, Keita Sutoh, Satoshi Nagaoka
JournalBioscience, biotechnology, and biochemistry (Biosci Biotechnol Biochem) Vol. 87 Issue 2 Pg. 197-207 (Jan 24 2023) ISSN: 1347-6947 [Electronic] England
PMID36521839 (Publication Type: Journal Article)
Copyright© The Author(s) 2022. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.
Chemical References
  • Oleic Acid
  • arginylproline
  • Peptide Transporter 1
  • Protamines
  • Peptides
  • Proline
Topics
  • Humans
  • Lipogenesis
  • Oleic Acid (pharmacology)
  • Hep G2 Cells
  • Peptide Transporter 1 (metabolism)
  • Protamines
  • Non-alcoholic Fatty Liver Disease (metabolism)
  • Peptides (metabolism)
  • Proline (metabolism)

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