STK25 regulates oxidative capacity and metabolic efficiency in adipose tissue
Journal article, 2018

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.

Oxidative stress

Brown adipose tissue

White adipose tissue

Lipid metabolism

Author

Silva Sütt

Sahlgrenska University Hospital

Emmelie Cansby

Sahlgrenska University Hospital

Alexandra Paul

Chalmers, Biology and Biological Engineering, Chemical Biology

Manoj Amrutkar

University of Oslo

Esther Nuñez-Durán

Sahlgrenska University Hospital

Nagaraj M. Kulkarni

Sahlgrenska University Hospital

Marcus Ståhlman

Wallenberg Lab.

Jan Borén

Wallenberg Lab.

Jurga Laurencikiene

Karolinska Institutet

Brian W. Howell

State University of New York Upstate Medical University

Sven Enerbäck

University of Gothenburg

Margit Mahlapuu

Sahlgrenska University Hospital

Journal of Endocrinology

0022-0795 (ISSN)

Vol. 238 3 187-202

Subject Categories

Cell Biology

Physiology

Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

DOI

10.1530/JOE-18-0182

More information

Latest update

12/7/2018