Lipodystrophy syndromes (LD) are a heterogeneous group of very rare congenital or acquired disorders characterized by a generalized or partial lack of adipose tissue. They are strongly associated with severe metabolic dysfunction due to ectopic fat accumulation in the liver and other organs and the dysregulation of several key adipokines, including leptin. Treatment with leptin or its analogues is therefore sufficient to reverse some of the metabolic symptoms of LD in patients and in mouse models through distinct mechanisms. Brown adipose tissue (BAT) thermogenesis has emerged as an important regulator of systemic metabolism in rodents and in humans, but it is poorly understood how leptin impacts BAT in LD. Here, we show in transgenic C57Bl/6 mice overexpressing sterol regulatory element-binding protein 1c in adipose tissue (Tg (aP2-nSREBP1c)), an established model of congenital LD, that daily subcutaneous administration of 3 mg/kg leptin for 6 to 8 weeks increases body temperature without affecting food intake or body weight. This is associated with increased protein expression of the thermogenic molecule uncoupling protein 1 (UCP1) and the sympathetic nerve marker tyrosine hydroxylase (TH) in BAT. These findings suggest that leptin treatment in LD stimulates BAT thermogenesis through sympathetic nerves, which might contribute to some of its metabolic benefits by providing a healthy reservoir for excess circulating nutrients.
Institut(e)Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
FörderungenEFSD Mentorship Programme - AstraZeneca University Leipzig, Medical Faculty Deutsche Diabetes Gesellschaft HI-MAG Deutsche Forschungsgemeinschaft (DFG, German Research foundation) Nachwuchsforderprogramm of the Medical Faculty, University of Leipzig Projektpreis der AG Diabetes und Niere 2020 by the Deutsche Diabetes Gesellschaft Novo Nordisk postdoctoral fellowship Karolinska Institutet, Stockholm, Sweden Njurfonden (Swedish Kidney Foundation) Stiftelsen Stig och Gunborg Westman Karolinska Institutet Research Foundation grant