Details

Autor(en) / Beteiligte

• Sleigh, Alison
• Stears, Anna
• Thackray, Kerrie
• Watson, Laura
• Gambineri, Alessandra
• Nag, Sath
• Campi, V. Irene
• Schoenmakers, Nadia
• Brage, Soren
• Carpenter, T. Adrian
• Murgatroyd, Peter R
• O'Rahilly, Stephen
• Kemp, Graham J
• Savage, David B

Titel

Mitochondrial Oxidative Phosphorylation Is Impaired in Patients with Congenital Lipodystrophy

Ist Teil von

• The journal of clinical endocrinology and metabolism, 2012-03, Vol.97 (3), p.E438-E442

Ort / Verlag

United States: Endocrine Society

Erscheinungsjahr

2012

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• Objective: Lipid accumulation in skeletal muscle and the liver is strongly implicated in the development of insulin resistance and type 2 diabetes, but the mechanisms underpinning fat accrual in these sites remain incompletely understood. Accumulating evidence of muscle mitochondrial dysfunction in insulin-resistant states has fuelled the notion that primary defects in mitochondrial fat oxidation may be a contributory mechanism. The purpose of our study was to determine whether patients with congenital lipodystrophy, a disorder primarily affecting white adipose tissue, manifest impaired mitochondrial oxidative phosphorylation in skeletal muscle. Research Design and Methods: Mitochondrial oxidative phosphorylation was assessed in quadriceps muscle using 31P-magnetic resonance spectroscopy measurements of phosphocreatine recovery kinetics after a standardized exercise bout in nondiabetic patients with congenital lipodystrophy and in age-, gender-, body mass index-, and fitness-matched controls. Results: The phosphocreatine recovery rate constant (k) was significantly lower in patients with congenital lipodystrophy than in healthy controls (P < 0.001). This substantial (∼35%) defect in mitochondrial oxidative phosphorylation was not associated with significant changes in basal or sleeping metabolic rates. Conclusions: Muscle mitochondrial oxidative phosphorylation is impaired in patients with congenital lipodystrophy, a paradigmatic example of primary adipose tissue dysfunction. This finding suggests that changes in mitochondrial oxidative phosphorylation in skeletal muscle could, at least in some circumstances, be a secondary consequence of adipose tissue failure. These data corroborate accumulating evidence that mitochondrial dysfunction can be a consequence of insulin-resistant states rather than a primary defect. Nevertheless, impaired mitochondrial fat oxidation is likely to accelerate ectopic fat accumulation and worsen insulin resistance.