PPARα Agonist, MHY3200, Alleviates Renal Inflammation during Aging via Regulating ROS/Akt/FoxO1 Signaling

• Published in: Molecules (Basel, Switzerland) Vol. 26; no. 11; p. 3197
• Main Authors: Kim, Min Jo, Kim, Dae Hyun, Bang, EunJin, Noh, Sang Gyun, Chun, Pusoon, Yokozawa, Takako, Moon, Hyung Ryong, Chung, Hae Young
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 26.05.2021; MDPI
• Subjects: Acetates - pharmacology; Acetates - therapeutic use; Age; Aging; Aging - drug effects; Agonists; Akt; AKT protein; Animals; Antioxidants; Atherosclerosis; Benzothiazole; Binding sites; Body Weight; Cell cycle; Cyclooxygenase-2; Diabetes; Enzymes; Forkhead protein; FOXO1 protein; Free radicals; Gene expression; Gene Expression Regulation; Glucose; Hydrogen bonds; Hypoglycemic Agents - pharmacology; Inflammation; Inflammation - drug therapy; Insulin; Insulin - metabolism; Kidney - drug effects; Kidney - pathology; Kidney diseases; Kidneys; Kinases; Lipids; Male; Metabolism; MHY3200; Nerve Tissue Proteins - metabolism; NF-κB; NF-κB protein; Oxidative stress; Phosphorylation; Physiology; PPAR alpha - agonists; PPAR alpha - metabolism; Protein Binding; Protein expression; Proteins; Proto-Oncogene Proteins c-akt - metabolism; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species - metabolism; Rodents; ROS; Signal Transduction - drug effects; Superoxide dismutase; Thiazoles - pharmacology; Thiazoles - therapeutic use; Time Factors; Transcription activation; Transcription factors; Triglycerides; Triglycerides - metabolism; NF-κB; Akt; aging; inflammation; MHY3200; ROS
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules26113197

PPARα is a ligand-dependent transcription factor and its activation is known to play an important role in cell defense through anti-inflammatory and antioxidant effects. MHY3200 (2-[4-(5-chlorobenzo[ ]thiazol-2-yl)phenoxy]-2,2-difluoroacetic acid), a novel benzothiazole-derived peroxisome proliferator-activated receptor α (PPARα) agonist, is a synthesized PPARα activator. This study examined the beneficial effects of MHY3200 on age-associated alterations in reactive oxygen species (ROS)/Akt/forkhead box (FoxO) 1 signaling in rat kidneys. Young (7-month-old) and old (22-month-old) rats were treated with MHY3200 (1 mg/kg body weight/day or 3 mg/kg body weight/day) for two weeks. MHY3200 treatment led to a notable decrease in triglyceride and insulin levels in serum from old rats. The elevated kidney ROS level, serum insulin level, and Akt phosphorylation in old rats were reduced following MHY3200 treatment; moreover, FoxO1 phosphorylation increased. MHY3200 treatment led to the increased level of FoxO1 and its target gene, MnSOD. MHY3200 suppressed cyclooxygenase-2 expression by activating PPARα and inhibiting the activation of nuclear factor-κB (NF-κB) in the kidneys of old rats. Our results suggest that MHY3200 ameliorates age-associated renal inflammation by regulating NF-κB and FoxO1 via ROS/Akt signaling.