Mitochondrial oxidative phosphorylation is impaired in patients with congenital lipodystrophy

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

Research output: Contribution to journalArticle

14 Citations (Scopus)

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 insulinresistant states rather than a primary defect. Nevertheless, impaired mitochondrial fat oxidation is likely to accelerate ectopic fat accumulation and worsen insulin resistance.

Original languageEnglish
JournalJournal of Clinical Endocrinology and Metabolism
Volume97
Issue number3
DOIs
Publication statusPublished - Mar 2012

Fingerprint

Lipodystrophy
Oxidative Phosphorylation
Muscle
Fats
Skeletal Muscle
Phosphocreatine
Insulin Resistance
Insulin
Tissue
Adipose Tissue
Defects
Muscles
White Adipose Tissue
Magnetic resonance spectroscopy
Quadriceps Muscle
Recovery
Oxidation
Type 2 Diabetes Mellitus
Medical problems
Body Mass Index

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Mitochondrial oxidative phosphorylation is impaired in patients with congenital lipodystrophy. / 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.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 97, No. 3, 03.2012.

Research output: Contribution to journalArticle

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 2012, 'Mitochondrial oxidative phosphorylation is impaired in patients with congenital lipodystrophy', Journal of Clinical Endocrinology and Metabolism, vol. 97, no. 3. https://doi.org/10.1210/jc.2011-2587
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. / Mitochondrial oxidative phosphorylation is impaired in patients with congenital lipodystrophy. In: Journal of Clinical Endocrinology and Metabolism. 2012 ; Vol. 97, No. 3.
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AU - Watson, Laura

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AU - Nag, Sath

AU - Campi, V. Irene

AU - Schoenmakers, Nadia

AU - Brage, Soren

AU - Carpenter, T. Adrian

AU - Murgatroyd, Peter R.

AU - O'Rahilly, Stephen

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