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Pigment epithelium-derived factor inhibits adipogenesis in 3T3-L1 adipocytes and protects against high-fat diet-induced obesity and metabolic disorders in mice
Journal
Translational Research
Journal Volume
210
Pages
26-42
Date Issued
2019
Author(s)
Abstract
Obesity is a major cause of metabolic syndrome and type II diabetes, and it presents with metabolic disorders, such as hyperglycemia, hyperlipidemia, and insulin resistance. Pigment epithelium-derived factor (PEDF), a protein isolated from retinal pigment epithelial cells, has multiple functions, including neuronal protection, antineoplastic effects, and anti-inflammatory activity. The aim of this study is to investigate the antiobesity effects of PEDF. The antiobesity effects of PEDF on fat accumulation, inflammation, energy expenditure, insulin resistance, and obesity-related physiological parameters and protein levels were assessed in high-fat diet (HFD)-induced obese mice in vivo and in 3T3-L1 adipocytes, palmitate (PA)-treated HepG2 cells, and C2C12 myotubes in vitro. In an in vivo assay, PEDF effectively decreased body weight gain, white adipose tissue mass, and inflammation and improved insulin resistance, dyslipidemia, and hyperglycemia in HFD-induced mice. In liver tissue, PEDF decreased lipid accumulation and fibrosis. In an in vitro assay, PEDF diminished the differentiation of 3T3-L1 preadipocytes. We also determined that PEDF promoted lipolysis and prolonged cell cycle progression, through the mTOR-S6K pathway and downstream transcription factors, such as peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding protein α (CEBP-α), and CEBP-β. In addition, PEDF decreased reactive oxygen species production in PA-induced HepG2 cells and improved glucose uptake ability in PA-induced HepG2 cells and C2C12 myotubes. In the present study, PEDF protected against HFD-induced obesity and metabolic disorders in mice, inhibited adipogenesis, and improved insulin resistance. These results provide a new potential treatment for obesity in the future. ? 2019 Elsevier Inc.
SDGs
Other Subjects
adiponectin; alanine aminotransferase; aspartate aminotransferase; CCAAT enhancer binding protein alpha; CCAAT enhancer binding protein beta; creatinine; cyclin A; cyclin B1; cyclin D1; glucose; high density lipoprotein; insulin; leptin; low density lipoprotein; mammalian target of rapamycin; perilipin; peroxisome proliferator activated receptor gamma; pigment epithelium derived factor; reactive oxygen metabolite; triacylglycerol; tumor necrosis factor; eye protein; nerve growth factor; palmitic acid; pigment epithelium-derived factor; S6 kinase; serine proteinase inhibitor; target of rapamycin kinase; 3T3-L1 cell line; adipogenesis; animal experiment; animal model; animal tissue; antiobesity activity; Article; body composition; body weight gain; body weight loss; cell cycle progression; cell differentiation; cell metabolism; cell proliferation; cell viability; controlled study; diet induced obesity; energy expenditure; glucose transport; Hep-G2 cell line; hyperglycemia; hyperlipidemia; in vitro study; in vivo study; inflammation; insulin resistance; insulin sensitivity; insulin tolerance test; lipid storage; lipolysis; liver fibrosis; metabolic disorder; mouse; nonalcoholic fatty liver; nonhuman; priority journal; proadipocyte; protein phosphorylation; retina pigment cell; treatment duration; white adipose tissue; adipocyte; adipogenesis; adipose tissue; animal; blood; C57BL mouse; cell clone; complication; drug effect; fatty liver; human; insulin resistance; lipid diet; male; metabolic disorder; metabolism; obesity; oxidative stress; pathology; signal transduction; skeletal muscle; skeletal muscle cell; 3T3-L1 Cells; Adipocytes; Adipogenesis; Adipose Tissue; Animals; Cell Proliferation; Clone Cells; Diet, High-Fat; Eye Proteins; Fatty Liver; Hep G2 Cells; Humans; Inflammation; Insulin Resistance; Male; Metabolic Diseases; Mice; Mice, Inbred C57BL; Muscle Fibers, Skeletal; Muscle, Skeletal; Nerve Growth Factors; Obesity; Oxidative Stress; Palmitic Acid; Ribosomal Protein S6 Kinases; Serpins; Signal Transduction; TOR Serine-Threonine Kinases
Publisher
Mosby Inc.
Type
journal article