Lipodystrophic syndromes are rare and heterogeneous diseases, characterized by a generalized or partial loss of adipose tissue (lipoatrophy) associated with metabolic complications usually associated with obesity: insulin-resistant diabetes, dyslipidemia, ovarian hyperandrogenism and non-alcoholic fatty liver disease.
Molecular genetic studies in different types of lipodystrophies showed that primary adipocyte alterations leading to impaired adipogenesis and/or defects of the metabolic functions of the adipocyte lipid droplet, were responsible for systemic metabolic alterations.
However, the broad spectrum of lipodystrophic clinical phenotypes, of genetic or acquired origin, and recent data have also pointed to important relationships between adipose tissue development, ageing, inflammation processes, DNA damage responses, and lipodystrophy and insulin resistance.
Non-specific therapeutic approaches aim to improve metabolic consequences of lipodystrophic syndromes. However, endocrine defects of lipodystrophic adipose tissue also participate to altered metabolic regulations, with leptin deficiency leading to increased appetite and ectopic storage of lipids in muscle and liver.
Leptin replacement therapy using s.c. injection of recombinant leptin (metreleptin) is the first specific therapy for lipodystrophies. Although it does not improve lipoatrophy itself, metreleptin was shown to significantly improve glucose and lipid alterations associated with lipodystrophies. Metreleptin was approved in 2014 by the FDA for generalized forms of lipodystrophies, and is available for the treatment of lipodystropic syndromes through compassionate programs in several European centers.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology