Protein kinase A induces UCP1 expression in specific adipose depots to increase energy expenditure and improve metabolic health
Autor: | Shriya Gandhi, Lorna M. Dickson, Barton Wicksteed, Ronald N. Cohen, Brian T. Layden |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
medicine.medical_specialty Physiology Adipose Tissue White Health Status Adipose tissue macrophages Adipose tissue White adipose tissue Biology Diet High-Fat Weight Gain Mice 03 medical and health sciences chemistry.chemical_compound Adipose Tissue Brown Insulin-Secreting Cells Physiology (medical) Internal medicine Adipocyte Glucose Intolerance Brown adipose tissue medicine Animals Lipolysis Uncoupling Protein 1 Adiposity Cyclic AMP-Dependent Protein Kinases Thermogenin Mice Inbred C57BL Obesity Diabetes and Energy Homeostasis 030104 developmental biology medicine.anatomical_structure Endocrinology Adipose Tissue chemistry Adipogenesis Adiponectin Insulin Resistance Energy Metabolism |
Zdroj: | American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 311:R79-R88 |
ISSN: | 1522-1490 0363-6119 |
Popis: | Adipose tissue PKA has roles in adipogenesis, lipolysis, and mitochondrial function. PKA transduces the cAMP signal downstream of G protein-coupled receptors, which are being explored for therapeutic manipulation to reduce obesity and improve metabolic health. This study aimed to determine the overall physiological consequences of PKA activation in adipose tissue. Mice expressing an activated PKA catalytic subunit in adipose tissue (Adipoq-caPKA mice) showed increased PKA activity in subcutaneous, epididymal, and mesenteric white adipose tissue (WAT) depots and brown adipose tissue (BAT) compared with controls. Adipoq-caPKA mice weaned onto a high-fat diet (HFD) or switched to the HFD at 26 wk of age were protected from diet-induced weight gain. Metabolic health was improved, with enhanced insulin sensitivity, glucose tolerance, and β-cell function. Adipose tissue health was improved, with smaller adipocyte size and reduced macrophage engulfment of adipocytes. Using metabolic cages, we found that Adipoq-caPKA mice were shown to have increased energy expenditure, but no difference to littermate controls in physical activity or food consumption. Immunoblotting of adipose tissue showed increased expression of uncoupling protein-1 (UCP1) in BAT and dramatic UCP1 induction in subcutaneous WAT, but no induction in the visceral depots. Feeding a HFD increased PKA activity in epididymal WAT of wild-type mice compared with chow, but did not change PKA activity in subcutaneous WAT or BAT. This was associated with changes in PKA regulatory subunit expression. This study shows that adipose tissue PKA activity is sufficient to increase energy expenditure and indicates that PKA is a beneficial target in metabolic health. |
Databáze: | OpenAIRE |
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