Effect of Simvastatin Treatment on Mitochondrial Function and Inflammatory Status of Human White Adipose Tissue

Autor: Ida Bager Christensen, Ida Blom, Tine Lovsø Dohlmann, Fabian Finger, Jørn W Helge, Zachary Gerhart-Hines, Flemming Dela, Steen Larsen
Rok vydání: 2023
Předmět:
Zdroj: The Journal of Clinical Endocrinology & Metabolism.
ISSN: 1945-7197
0021-972X
DOI: 10.1210/clinem/dgad259
Popis: Background Statin therapy has shown pleiotropic effects affecting both mitochondrial function and inflammatory status. However, few studies have investigated the concurrent effects of statin exposure on mitochondrial function and inflammatory status in human subcutaneous white adipose tissue. Objectives In a cross-sectional study, we investigated the effects of simvastatin on mitochondrial function and inflammatory status in subcutaneous white adipose tissue of 55 human participants: 38 patients (19 females/19 males) in primary prevention with simvastatin (> 40 mg/d, > 3 mo) and 17 controls (9 females/8 males) with elevated plasma cholesterol. The 2 groups were matched on age, body mass index, and maximal oxygen consumption. Methods Anthropometrics and fasting biochemical characteristics were measured. Mitochondrial respiratory capacity was assessed in white adipose tissue by high-resolution respirometry. Subcutaneous white adipose tissue expression of the inflammatory markers IL-6, chemokine (C-C motif) ligand 2 (CCL2), CCL-5, tumor necrosis factor-α, IL-10, and IL-4 was analyzed by quantitative PCR. Results Simvastatin-treated patients showed lower plasma cholesterol (P < .0001), low-density lipoprotein (P < .0001), and triglyceride levels (P = .0116) than controls. Simvastatin-treated patients had a lower oxidative phosphorylation capacity of mitochondrial complex II (P = .0001 when normalized to wet weight, P < .0001 when normalized to citrate synthase activity [intrinsic]), and a lower intrinsic mitochondrial electron transport system capacity (P = .0004). Simvastatin-treated patients showed higher IL-6 expression than controls (P = .0202). Conclusion Simvastatin treatment was linked to mitochondrial respiratory capacity in human subcutaneous white adipose tissue, but no clear link was found between statin exposure, respiratory changes, and inflammatory status of adipose tissue.
Databáze: OpenAIRE
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