Thèse : Camille VATIER – Traitement par leptine recombinante dans les syndromes lipodystrophiques génétiques: effets sur le métabolisme glucido-lipidique

(Équipe Fève)

Leptin deficiency, which correlates with the decreased amount of body fat, was shown to contribute to lipodystrophy-associated metabolic complications. Recombinant leptin (metreleptin) therapy, approved in the US, Japan and since 2018 in the UE for the treatment of lipodystrophic syndromes, decreases insulin resistance, hyperglycemia, dyslipidemia and liver steatosis in hypoleptinemic lipodystrophic patients, in part independently of an improved control of deregulated eating behavior. This work showed that metreleptin improved not only insulin sensitivity, but also insulin secretion in patients with genetically-determined lipodystrophy. One-year metreleptin therapy also significantly decreased the plasma concentrations of proprotein convertase subtilisin/kexin type 9 (PCSK9) and proatherogenic apolipoprotein B. These results further stress that metreleptin needs to be integrated in the therapeutic strategy for patients with lipodystrophic syndromes.