NIH Research Festival
Lipodystrophy is characterized by selective loss of adipose tissue, which leads to low levels of the adipocyte-derived hormone, leptin. Low levels of leptin send a starvation signal to the brain, causing hyperphagia along with metabolic abnormalities including extreme insulin resistance, hypertriglyceridemia, and ectopic lipid deposition. Leptin hormone replacement therapy for patients with lipodystrophy reduces food intake and ameliorates these metabolic complications. However, it is not known whether leptin improves metabolic complications of lipodystrophy solely via reductions in food intake, or if it has food-intake independent effects. To explore this, we studied 22 patients with lipodystrophy during periods with and without leptin treatment, with food intake held constant in both conditions. Changes in insulin sensitivity were assessed by euglycemic hyperinsulinemic clamps during on- and off-leptin periods. In the eight patients who were first studied ON leptin, then stopped leptin, insulin sensitivity decreased from 9.9 ± 4.1 ON leptin to 5.7 ± 1.5 mg/kgFFM/min OFF leptin (p=0.017). In the fourteen patients who were first studied OFF leptin, then started leptin, insulin sensitivity increased from 2.9 ± 1.7 OFF leptin to 4.1 ± 1.7 ON leptin (p=0.007). Long-term leptin treatment effects were evaluated in 14 patients who first started OFF leptin, insulin sensitivity increased from 2.9 ± 1.7 OFF leptin to 5.7 ± 3.9 ON leptin after 6-12 months of treatment with food intake ad libitum (p=0.04). In patients with lipodystrophy, leptin therapy increases insulin sensitivity independent of its effects on food intake.
Scientific Focus Area: Research Support Services
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