Nature communications, 2020-04, Vol.11 (1), p.1642-1642, Article 1642
2020
Details
- Autor(en) / Beteiligte
- Titel
- ASK1 inhibits browning of white adipose tissue in obesity
- Ist Teil von
- Nature communications, 2020-04, Vol.11 (1), p.1642-1642, Article 1642
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2020
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Increasing energy expenditure via induction of adipose tissue browning has become an appealing strategy to treat obesity and associated metabolic complications. Herein, we identify adipocyte-expressed apoptosis signal-regulating kinase 1 (ASK1) as regulator of adipose tissue browning. High fat diet-fed adipocyte-specific ASK1 knockout mice reveal increased UCP1 protein levels in inguinal adipose tissue concomitant with elevated energy expenditure, reduced obesity and ameliorated glucose tolerance compared to control littermates. In addition, ASK1-depletion blunts LPS-mediated downregulation of isoproterenol-induced UCP1 in subcutaneous fat both in vitro and in vivo. Conversely, adipocyte-specific ASK1 overexpression in chow-fed mice attenuates cold-induced UCP1 protein levels in inguinal fat. Mechanistically, ASK1 phosphorylates interferon regulatory factor 3 (IRF3) resulting in reduced Ucp1 expression. Taken together, our studies unravel a role of ASK1 in mediating the inhibitory effect of caloric surplus or LPS-treatment on adipose tissue browning. Adipocyte ASK1 might be a pharmacological target to combat obesity and associated morbidities.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-1723eISSN: 2041-1723DOI: 10.1038/s41467-020-15483-7Titel-ID: cdi_doaj_primary_oai_doaj_org_article_a5f0fcf02ab1420cbe65f5ab4e73cc5e
- Format
- –
- Schlagworte
- Adipocytes, Adipose tissue, Adipose Tissue, Brown - metabolism, Adipose Tissue, White - metabolism, Animals, Apoptosis, Browning, Complications, Depletion, Energy expenditure, Energy Metabolism, Female, Glucose tolerance, High fat diet, Humans, Interferon, Interferon regulatory factor, Interferon regulatory factor 3, Interferon Regulatory Factor-3 - genetics, Interferon Regulatory Factor-3 - metabolism, Isoproterenol, Kinases, Lipopolysaccharides, Male, MAP kinase, MAP Kinase Kinase Kinase 5 - genetics, MAP Kinase Kinase Kinase 5 - metabolism, Mice, Mice, Knockout, Obesity, Obesity - genetics, Obesity - metabolism, Phosphorylation, Proteins, Receptor mechanisms, Regulatory mechanisms (biology), Thermogenesis, Uncoupling Protein 1 - genetics, Uncoupling Protein 1 - metabolism