Loss of ADAMTS5 enhances brown adipose tissue mass and promotes browning of white adipose tissue via CREB signaling
| Autor: | Johan Van Lint, Lotte Geys, Mathias Cobbaut, Dries Bauters, H. Roger Lijnen, Bianca Hemmeryckx |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male HFD high-fat diet ADAMTS A disintesgrin and metalloproteinase with a thrombospondin type-1 motif Adipose tissue White adipose tissue Brown adipose tissue %ID/g percentage injected dose per gram chemistry.chemical_compound Mice 0302 clinical medicine Adipose Tissue Brown Adipocyte Cyclic AMP Response Element-Binding Protein Cells Cultured WAT white adipose tissue Thermogenesis Thermogenin ECM extracellular matrix medicine.anatomical_structure 030220 oncology & carcinogenesis ADAMTS5 GON gonadal Original Article β3-AR beta-3 adrenergic receptor Beta-3 adrenergic receptor CAMP Responsive Element Binding Protein medicine.medical_specialty lcsh:Internal medicine Adipose Tissue White SUV standardized uptake value Adrenergic beta-3 Receptor Agonists Dioxoles Biology TLG total lesion glycolysis 03 medical and health sciences Internal medicine CREB cAMP responsive element-binding protein AT adipose tissue UCP1 uncoupling protein 1 medicine Animals Obesity lcsh:RC31-1245 Molecular Biology Beige Cell Biology BAT brown adipose tissue SC subcutaneous Mice Inbred C57BL 030104 developmental biology Endocrinology chemistry ADAMTS5 Protein Browning Energy Metabolism |
| Zdroj: | Molecular Metabolism, Vol 6, Iss 7, Pp 715-724 (2017) Molecular Metabolism |
| ISSN: | 2212-8778 |
| Popis: | Objective A potential strategy to treat obesity – and the associated metabolic consequences – is to increase energy expenditure. This could be achieved by stimulating thermogenesis through activation of brown adipose tissue (BAT) and/or the induction of browning of white adipose tissue (WAT). Over the last years, it has become clear that several metalloproteinases play an important role in adipocyte biology. Here, we investigated the potential role of ADAMTS5. Methods Mice deficient in ADAMTS5 (Adamts5−/−) and wild-type (Adamts5+/+) littermates were kept on a standard of Western-type diet for 15 weeks. Energy expenditure and heat production was followed by indirect calorimetry. To activate thermogenesis, mice were treated with the β3-adrenergic receptor (β3-AR) agonist CL-316,243 or alternatively, exposed to cold for 2 weeks. Results Compared to Adamts5+/+ mice, Adamts5−/− mice have significantly more interscapular BAT and marked browning of their subcutaneous (SC) WAT. Thermogenic pathway analysis indicated, in the absence of ADAMTS5, enhanced β3-AR signaling via activation of the cAMP response element-binding protein (CREB). Additional β3-AR stimulation with CL-316,243 promoted browning of WAT in Adamts5+/+ mice but had no additive effect in Adamts5−/− mice. However, cold exposure induced more pronounced browning of WAT in Adamts5−/− mice. Conclusions These data indicate that ADAMTS5 plays a functional role in development of BAT and browning of WAT. Hence, selective targeting of ADAMTS5 could provide a novel therapeutic strategy for treatment/prevention of obesity and metabolic diseases. Highlights • Mice deficient in ADAMTS5 have elevated interscapular brown adipose tissue mass. • ADAMTS5 deficient mice show increased browning of their white adipose tissue. • The thermogenic profile is enhanced via adrenergic signaling and CREB activation. • ADAMTS5 seems an attractive therapeutic target for metabolic diseases. |
| Databáze: | OpenAIRE |
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