Leptin Improves Parameters of Brown Adipose Tissue Thermogenesis in Lipodystrophic Mice

• Published in: Nutrients Vol. 13; no. 8; p. 2499
• Main Authors: Hoffmann, Annett, Ebert, Thomas, Hankir, Mohammed K, Flehmig, Gesine, Klöting, Nora, Jessnitzer, Beate, Lössner, Ulrike, Stumvoll, Michael, Blüher, Matthias, Fasshauer, Mathias, Tönjes, Anke, Miehle, Konstanze, Kralisch, Susan
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 22-07-2021; MDPI
• Subjects: Adipocytes; Adipose tissue; Adipose tissue (brown); Adipose Tissue, Brown - drug effects; Adipose Tissue, Brown - innervation; Adipose Tissue, Brown - metabolism; Adipose tissues; Analysis; Animal models; Animals; Antibodies; Body fat; Body temperature; Body weight; brown adipose tissue; Disease Models, Animal; Ethylenediaminetetraacetic acid; Food; Food intake; Genetic disorders; Genetic engineering; Glucose; Homeostasis; Hydroxylase; Insulin; Leptin; Leptin - pharmacology; Lipodystrophy; Lipodystrophy - drug therapy; Lipodystrophy - genetics; Lipodystrophy - metabolism; Lipodystrophy - physiopathology; Liver; Low density lipoprotein receptors; Male; Medicin och hälsovetenskap; Metabolism; Mice; Mice, Inbred C57BL; Mice, Transgenic; Nutrients; Organs; Physiological aspects; Plasma; Protein binding; Proteins; Receptors, LDL - genetics; Receptors, LDL - metabolism; Signs and symptoms; Software; Sterol Regulatory Element Binding Protein 1 - genetics; Sterol Regulatory Element Binding Protein 1 - metabolism; Sterol regulatory element-binding protein; Sterol regulatory element-binding protein 1c; Sympathetic nerves; sympathetic nervous system; Sympathetic Nervous System - drug effects; Sympathetic Nervous System - metabolism; Sympathetic Nervous System - physiopathology; Thermogenesis; Transgenic mice; Triglycerides; Tyrosine; Tyrosine 3-monooxygenase; Tyrosine 3-Monooxygenase - metabolism; Uncoupling protein 1; Uncoupling Protein 1 - metabolism; Germany; United Kingdom > UK; United States > US; uncoupling protein 1; thermogenesis; brown adipose tissue; leptin; sympathetic nervous system; lipodystrophy
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu13082499

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.