Changes After Leptin Administration in Partial Lipodystrophy and Factors Associated With Hepatic and Metabolic Response.

CONTEXT: Partial lipodystrophy (PL) is a rare disease characterized by selective loss of subcutaneous fat.

OBJECTIVE

To evaluate changes in apolipoproteins, hepatokines, hormones, appetite regulators, and inflammatory markers in patients with PL treated with leptin, assess postprandial metabolism and 24-hour dynamics, and identify predictors of hepatic and metabolic response to therapy.

METHODS

We studied 19 subjects from our previous clinical study (NCT01679197), which investigated the effect of leptin on metabolic dysfunction-associated steatohepatitis associated with PL. A mixed-meal test was performed in a subgroup of 14 patients, and paired 24-hour frequent sampling with standardized meals was completed in 5 individuals.

RESULTS

Leptin treatment led to reductions in apolipoproteins B, CII, CIII, and E (P < .05). Levels of ANGPTL3 tended to decrease after leptin treatment (P = .079). The mixed-meal test revealed significant reductions in triglyceride area under the curve (P = .017) and glucose excursions at several postmeal time points (P < .05). The immediate GIP secretion in response to a meal attenuated after leptin therapy (P = .005 at 60 minutes). Ghrelin levels showed an increase after leptin administration. The response to leptin treatment was associated with several factors, including baseline carbohydrate intake, leptin and triglyceride levels and triglyceride-rich apolipoproteins, and changes in triglyceride-rich apolipoproteins (P < .05 for all). Changes in IGF-1 levels were correlated with improvements in metabolic and liver parameters (P < .05).

CONCLUSION

Leptin therapy modulates lipid metabolism, postprandial glucose regulation, and appetite signaling in patients with PL, with responses associated with metabolic parameters and carbohydrate intake.