Skeletal muscle morphology and exercise response in congenital generalized lipodystrophy.

Abstract

OBJECTIVE: Congenital generalized lipodystrophy (CGL) is an autosomal recessive genetic disorder characterized by almost complete absence of adipose tissue, muscular appearance, and severe insulin resistance since birth. We investigated whether insulin resistance in CGL patients is associated with abnormal muscle morphology and whether increased muscularity imparts increased muscle strength and exercise capacity RESEARCH DESIGN AND METHODS: We obtained quadriceps muscle biopsies to study muscle fiber types and capillary density in three African-American women (aged 17-20 years) with CGL. We also assessed quadriceps muscle strength, muscle metabolism, and maximal O2 consumption in the patients. RESULTS: Quadriceps muscle biopsies revealed a markedly higher percentage of type II (fast-twitch glycolytic) muscle fibers in patients with CGL versus sedentary young women (75-78 vs. 47-57%, respectively). The capillary-to-fiber ratio (2.7-3.0), however, was normal. Cross-sectional areas of type I (slow-twitch oxidative) (1,262-2,685 microm2) and type II (2,304-3,594 microm2) fibers were far below the normal values (3,811-4,310 and 3,115-4,193 microm2, respectively), suggesting muscle hyperplasia but not hypertrophy The quadriceps muscle strength, as measured by Cybex, was below average; the maximal O2 consumption (23-32 ml x kg(-1) x min(-1)) was also below average. 31P nuclear magnetic resonance spectroscopy of the forearm muscles revealed normal pH and metabolic responses to static and dynamic exercises. CONCLUSIONS: We conclude that insulin resistance in patients with CGL is associated with an increased proportion of type II muscle fibers but not reduced capillary density. Increased muscularity in CGL is due to muscle hyperplasia and is not associated with increased muscle strength.

Muscle-Strengthening Activity and Its Association With Insulin Sensitivity

“…In another study, the number of capillaries per length of fiber perimeter was increased after both resistance and aerobic training in men aged 65-74 years, paralleling the changes in VO 2max , and there was a significant positive correlation between the change in capillary supply and VO 2max (22). In brief, the mechanisms behind the effect of strength training seem similar to those seen with aerobic training, even though MSAs mainly recruit type II muscle (fast-twitch fibers), especially type IIb fibers, that are less sensitive to insulin than type I muscle (slow-twitch fibers) (23).…”

Altered miRNA processing disrupts brown/white adipocyte determination and associates with lipodystrophy

“…While the exact mechanism of the latter is unknown at present, muscular hypertrophy is observed in some patients with both generalized and partial lipodystrophy (60)(61)(62). KO of dicer in fat also changes sensitivity to oxidative stress at the whole-body level in interesting ways.…”

Congenital generalized lipodystrophy

“…O estudo morfológico e funcional da musculatura esquelética de pacientes com essa doença sugere que a acentuada massa muscular seja decorrente de um processo hiperplásico e não hipertrófico , sem qualquer associação com aumento de força 8 .…”