1947-P: Comparative Effects of PCSK9 Inhibitor and High-Dose Atorvastatin on Mitochondria of Red Muscle Fibers in Obese Female Rats
| Autor: | Busarin Arunsak, Chanisa Thonusin, Nipon Chattipakorn, Wasana Pratchayasakul, Patchareeya Amput, Siriporn C. Chattipakorn, Siripong Palee |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Mitochondrial ROS
Soleus muscle medicine.medical_specialty Normal diet Chemistry Endocrinology Diabetes and Metabolism Atorvastatin Skeletal muscle Mitochondrion Lipid peroxidation chemistry.chemical_compound Endocrinology medicine.anatomical_structure Internal medicine Internal Medicine medicine Mitochondrial fission medicine.drug |
| Zdroj: | Diabetes. 68 |
| ISSN: | 1939-327X 0012-1797 |
| Popis: | Obesity and dyslipidemia cause mitochondrial dysfunction of skeletal muscle. Low dose atorvastatin impairs mitochondrial function of white muscle fibers but does not damage that of red muscle fibers. However, the effects of PCSK9 inhibitors and high dose atorvastatin on mitochondrial function of red muscle fibers have not been identified. Twenty-four female rats (180-200 g) were divided into 2 groups. Six rats were fed with normal diet (ND) and 18 rats were fed with high-fat diet (HFD) for 15 weeks. At week 12, ND-fed rats were treated with vehicle (NDV), while HFD-fed rats were equally subdivided and treated with either vehicle (HFV), 4 mg/kg/day of PCSK9 inhibitor (HFP), or 40 mg/kg/day of atorvastatin (HFA) for another 3 weeks. HFV rats developed obesity and dyslipidemia, as indicated by increased weight, visceral fat, and total cholesterol. Treatment with atorvastatin and PCSK9 inhibitor improved obesity and dyslipidemia. Increased lipid peroxidation (MDA), mitochondrial fission (pDrp1/Drp1), mitochondrial ROS production, and mitochondrial membrane depolarization were found in soleus muscle of HFV rats. Treatment with atorvastatin and PCSK9 inhibitor similarly improved lipid peroxidation and mitochondrial fission. However, only PCSK9 inhibitor improved mitochondrial ROS production and mitochondrial membrane depolarization. Our findings suggest that obesity increases lipid peroxidation, mitochondrial fission, mitochondrial ROS production, and mitochondrial membrane depolarization in red muscle fibers. PCSK9 inhibitor attenuates those deleterious effects of obesity. High dose atorvastatin improves lipid peroxidation and mitochondrial fission, but does not attenuate obesity-induced mitochondrial ROS production and mitochondrial membrane depolarization in red muscle fibers. The results imply that high dose atorvastatin causes adverse effects on red muscle fibers despite its benefit on the improvement of obesity and dyslipidemia. Disclosure C. Thonusin: None. S. Palee: None. B. Arunsak: None. P. Amput: None. W. Pratchayasakul: None. N. Chattipakorn: None. S.C. Chattipakorn: None. Funding Thailand Research Fund |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|