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- Title
Mitochondrial oxidative phosphorylation is impaired in patients with congenital lipodystrophy.
- Authors
Sleigh A; Stears A; Thackray K; Watson L; Gambineri A; Nag S; Campi VI; Schoenmakers N; Brage S; Carpenter TA; Murgatroyd PR; O'Rahilly S; Kemp GJ; Savage DB; Sleigh, Alison; Stears, Anna; Thackray, Kerrie; Watson, Laura; Gambineri, Alessandra; Nag, Sath
- Abstract
<bold>Objective: </bold>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.<bold>Research Design and Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Publication
Journal of Clinical Endocrinology & Metabolism, 2012, Vol 97, Issue 3, pE438
- ISSN
0021-972X
- Publication type
journal article
- DOI
10.1210/jc.2011-2587