title: Atorvastatin and rosuvastatin improve physiological parameters and alleviate immune dysfunction in metabolic disorders.
abstract: This study was designed to characterize the potential therapeutic effects of two statin drugs commonly used to treat dyslipidemia in inflammation-linked metabolic disorders related to type 2 diabetes. Atorvastatin (10 mg/kg/day) and rosuvastatin (3 mg/kg/day) were administered to mice with diet-induced obesity (DIO). The statins lowered serum total and LDL cholesterol levels, and improved the atherogenic index and cardiac risk index. Furthermore, the drugs decreased fasting glucose levels, improved glucose tolerance, and decreased fat tissue weight and adipocyte size; this was accompanied by an overall body weight loss tendency. The statins also improved antigen-specific immunity. The killing activity of cytotoxic T cells and exacerbation of IgG secretion levels were considerably normalized. Most importantly, serum tumor necrosis factor-α and interleukin 6 levels decreased, while their RNA expression levels in fat tissue were regulated by the statins as well. This study is the first to indicate that low doses of atorvastatin and rosuvastatin, the dosing regimen for which has been controversial, could significantly improve diabetes-related metabolic disorders, and could modulate pro-inflammatory cytokines, alleviating inflammation and simultaneously restoring overall humoral and cell-mediated immunity.
authors: College of Pharmacy, Sahmyook University, Seoul 01795, Republic of Korea.
authors: Sungwon
authors: S
authors: Lee
authors: College of Pharmacy, Sahmyook University, Seoul 01795, Republic of Korea.
authors: Youngjoo
authors: Y
authors: Lee
authors: College of Pharmacy, Sahmyook University, Seoul 01795, Republic of Korea.
authors: Jiyeon
authors: J
authors: Kim
authors: College of Pharmacy, Sahmyook University, Seoul 01795, Republic of Korea.
authors: Jinho
authors: J
authors: An
authors: College of Pharmacy, Sahmyook University, Seoul 01795, Republic of Korea.
authors: Kwanghee
authors: K
authors: Kim
authors: College of Pharmacy, Sahmyook University, Seoul 01795, Republic of Korea.
authors: Heetae
authors: H
authors: Lee
authors: College of Pharmacy, Sahmyook University, Seoul 01795, Republic of Korea.
authors: Hyunseok
authors: H
authors: Kong
authors: College of Pharmacy, Sahmyook University, Seoul 01795, Republic of Korea.
authors: Youngcheon
authors: Y
authors: Song
authors: College of Pharmacy, Sahmyook University, Seoul 01795, Republic of Korea. Electronic address: kimkj@syu.ac.kr.
authors: Kyungjae
authors: K
authors: Kim
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000069059:Atorvastatin / Q000494:pharmacology / Q000627:therapeutic use*; D016207:Cytokines / Q000097:blood; D059305:Diet, High-Fat; D000939:Epitopes; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D007109:Immunity; D018836:Inflammation Mediators / Q000378:metabolism; D050356:Lipid Metabolism; D008297:Male; D008659:Metabolic Diseases / Q000097:blood / Q000188:drug therapy* / Q000276:immunology* / Q000503:physiopathology; D008810:Mice, Inbred C57BL; D009929:Organ Size; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000068718:Rosuvastatin Calcium / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D016207:Cytokines; D000939:Epitopes; D018836:Inflammation Mediators; D012333:RNA, Messenger; D000068718:Rosuvastatin Calcium; D000069059:Atorvastatin; D005947:Glucose
keywords: Atorvastatin; Immune restoration; In vivo CTL assay; Rosuvastatin; Type 2 diabetes