Dataset Information

Mitochondrial oxidative phosphorylation is impaired in patients with congenital lipodystrophy.

ABSTRACT:

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.

SUBMITTER: Sleigh A

PROVIDER: S-EPMC3380089 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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Publications

Mitochondrial oxidative phosphorylation is impaired in patients with congenital lipodystrophy.

Sleigh Alison A Stears Anna A Thackray Kerrie K Watson Laura L Gambineri Alessandra A Nag Sath S Campi V Irene VI Schoenmakers Nadia N Brage Soren S Carpenter T Adrian TA Murgatroyd Peter R PR O'Rahilly Stephen S Kemp Graham J GJ Savage David B DB

The Journal of clinical endocrinology and metabolism 20120111 3

<h4>Objective</h4>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 w ...[more]

PMID: 22238385

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Dataset Information

Mitochondrial oxidative phosphorylation is impaired in patients with congenital lipodystrophy.

Objective

Research design and methods

Results

Conclusions

Publications

Mitochondrial oxidative phosphorylation is impaired in patients with congenital lipodystrophy.

Similar Datasets

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