Background: Familial Partial Lipodystrophy, Dunnigan variety (FPLD) is characterized by post-natal fat loss leading to severe insulin resistance. Affected individuals also display striking skeletal muscle hypertrophy, but there is limited information on muscle function and energy metabolism. We therefore systematically investigated muscle and mitochondrial function in 6 individuals with FPLD and 6 matched controls.

Methods: Body composition and intramyocellular lipid content (IMCL) were assessed by DEXA and magnetic resonance spectroscopy, respectively. Maximal voluntary strength and fatigue were assessed for both recumbent leg press and seated chest press. Vastus lateralis muscle biopsies were obtained prior to and following a high fat (40%) mixed-meal. Oxygen consumption in isolated mitochondria was measured using substrates supporting carbohydrate or lipid-based respiration. Insulin Sensitivity Index (SI) was calculated by minimal modelling.

Results: Individuals with FPLD had significantly lower SI, lower body fat content, and higher lean mass. Peak leg press and chest press force were not different, but FPLD individuals had earlier fatigue during chest press (number of repetitions: 15 ± 0.6 vs. 20 ± 0.3, p = 0.01). They also had a 50-60% decrease in state 3 respiration measured using substrates supporting lipid-based respiration (p = 0.04). Further, mitochondrial oxidative capacity showed a strong correlation with muscle fatigue (r = 0.76, p = 0.003), and inversely correlated with fasting and post-prandial lipemia and measures of insulin resistance.

Conclusion: Individuals with FPLD have higher lean body mass and lower insulin sensitivity. Despite preserved peak muscle strength, they demonstrated earlier muscle fatigue. Decreased mitochondrial fatty acid oxidative capacity, likely related to elevated IMCL, may contribute to muscular and metabolic abnormalities.


V. Simha: None. I.R. Lanza: None. N. LeBrasseur: None. K. Klaus: None. J. Port: None. M.C. Laurenti: Other Relationship; Self; GlySens Incorporated. C. Cobelli: Research Support; Self; Sanofi-Aventis. Advisory Panel; Self; Novo Nordisk Inc.. K. Nair: None.

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