Peroxiredoxin 4 inhibits insulin-induced adipogenesis through regulation of ER stress in 3T3-L1 cells

• Published in: Molecular and cellular biochemistry 2020-05, Vol.468 (1-2), p.97-109
• Main Authors: Kim, Jae Yeop, Kim, Mi Hye, Lee, Hong Jun, Huh, Jae-Won, Lee, Sang-Rae, Lee, Hyun-Shik, Lee, Dong-Seok
• Format: Article
• Language: English
• Subjects: 3T3-L1 Cells; Accumulation; Adipocytes; Adipocytes - drug effects; Adipocytes - enzymology; Adipocytes - metabolism; Adipogenesis; Adipogenesis - drug effects; Adipogenesis - genetics; Animals; Biochemistry; Biomedical and Life Sciences; Calcium - metabolism; Cardiology; Cholesterol; Developed countries; Differentiation; Endoplasmic reticulum; Endoplasmic Reticulum - metabolism; Endoplasmic Reticulum Stress - drug effects; Endoplasmic Reticulum Stress - genetics; Gene expression; Gene Expression Regulation - drug effects; Gene Expression Regulation - genetics; Global health; Insulin; Insulin - pharmacology; Life Sciences; Lipid Metabolism - genetics; Lipids; Medical Biochemistry; Metabolic disorders; Mice; Obesity; Obesity - genetics; Obesity - metabolism; Oncology; Peroxiredoxin; Peroxiredoxins - genetics; Peroxiredoxins - metabolism; Reactive oxygen species; Reactive Oxygen Species - metabolism; Scavenging
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-020-03714-w

Obesity was originally considered a disease endemic to developed countries but has since emerged as a global health problem. Obesity is characterized by abnormal or excessive lipid accumulation (World Health Organization, WHO) resulting from pre-adipocyte differentiation (adipogenesis). The endoplasmic reticulum (ER) produces proteins and cholesterol and shuttles these compounds to their target sites. Many studies have implicated ER stress, indicative of ER dysfunction, in adipogenesis. Reactive oxygen species (ROS) are also known to be involved in pre-adipocyte differentiation. Prx4 specific to the ER lumen exhibits ROS scavenging activity, and we thereby focused on ER-specific Prx4 in tracking changes in adipocyte differentiation and lipid accumulation. Overexpression of Prx4 reduced ER stress and suppressed lipid accumulation by regulating adipogenic gene expression during adipogenesis. Our results demonstrate that Prx4 inhibits ER stress, lowers ROS levels, and attenuates pre-adipocyte differentiation. These findings suggested enhancing the activity of Prx4 may be helpful in the treatment of obesity; the data also support the development of new therapeutic approaches to obesity and obesity-related metabolic disorders. Graphic abstract