4.5 Article

STK25 regulates oxidative capacity and metabolic efficiency in adipose tissue

Journal

JOURNAL OF ENDOCRINOLOGY
Volume 238, Issue 3, Pages 187-202

Publisher

BIOSCIENTIFICA LTD
DOI: 10.1530/JOE-18-0182

Keywords

brown adipose tissue; white adipose tissue; lipid metabolism; oxidative stress

Funding

  1. Swedish Research Council
  2. Novo Nordisk Foundation
  3. Swedish Heart and Lung Foundation
  4. Diabetes Wellness Network Sweden
  5. Estonian Research Council
  6. Swedish Diabetes Foundation
  7. Royal Society of Arts and Sciences in Gothenburg
  8. Wiberg Foundation
  9. Adlerbert Research Foundation
  10. I. Hultman Foundation
  11. S. and E. Goljes Foundation
  12. West Sweden ALF Program
  13. F. Neubergh Foundation
  14. I.-B. and A. Lundbergs Research Foundation
  15. Swedish Innovation Agency Vinnova
  16. Torsten Soderbergs Foundation
  17. European Foundation for the Study of Diabetes/Lilly European Diabetes Research Programme
  18. L. och J. Gronbergs Foundation
  19. European Foundation for the Study of Diabetes and Novo Nordisk Partnership for Diabetes Research in Europe
  20. European Union [607842]
  21. Prof. Nanna Svartz Foundation

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Whole-body energy homeostasis at over-nutrition critically depends on how well adipose tissue remodels in response to excess calories. We recently identified serine/threonine protein kinase (STK) 25 as a critical regulator of ectopic lipid storage in non-adipose tissue and systemic insulin resistance in the context of nutritional stress. Here, we investigated the role of STK25 in regulation of adipose tissue dysfunction in mice challenged with a high-fat diet. We found that overexpression of STK25 in high-fat-fed mice resulted in impaired mitochondrial function and aggravated hypertrophy, inflammatory infiltration and fibrosis in adipose depots. Reciprocally, Stk25-knockout mice displayed improved mitochondrial function and were protected against diet-induced excessive fat storage, meta-inflammation and fibrosis in brown and white adipose tissues. Furthermore, in rodent HIB-1B cell line, STK25 depletion resulted in enhanced mitochondrial activity and consequently, reduced lipid droplet size, demonstrating an autonomous action for STK25 within adipocytes. In summary, we provide the first evidence for a key function of STK25 in controlling the metabolic balance of lipid utilization vs lipid storage in brown and white adipose depots, suggesting that repression of STK25 activity offers a potential strategy for establishing healthier adipose tissue in the context of chronic exposure to dietary lipids.

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