Gene expression levels of Casein kinase 1 (CK1) isoforms are correlated to adiponectin levels in adipose tissue of morbid obese patients and site-specific phosphorylation mediated by CK1 influences multimerization of adiponectin.
White adipose tissue has now been recognized as an important endocrine organ secreting bioactive molecules termed adipocytokines. In obesity, anti-inflammatory adipocytokines like adiponectin are decreased while pro-inflammatory factors are over-produced. These changes contribute to the development of insulin resistance and obesity-associated diseases. Since members of the casein kinase 1 (CK1) family are involved in the regulation of various signaling pathways we ask here whether they are able to modulate the functions of adiponectin. We show that CK1δ and ε are expressed in adipose tissue and that the expression of CK1 isoforms correlates with that of adiponectin. Furthermore, adiponectin co-immunoprecipitates with CK1δ and CK1ε and is phosphorylated by CK1δ at serine 174 and threonine 235, thereby influencing the formation of adiponectin oligomeric complexes. Furthermore, inhibition of CK1δ in human adipocytes by IC261 leads to an increase in basal and insulin-stimulated glucose uptake. In summary, our data indicate that site-specific phosphorylation of adiponectin, especially at sites targeted by CK1δ in vitro, provides an additional regulatory mechanism for modulating adiponectin complex formation and function.
Department of General and Visceral Surgery, University of Ulm, Albert-Einstein-Allee 23, 89081 Ulm, Germany.
Pengfei
P
Xu
Divison of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, University of Ulm, Eythstrasse 24, 89075 Ulm, Germany.
Pamela
P
Fischer-Posovszky
Department of General and Visceral Surgery, University of Ulm, Albert-Einstein-Allee 23, 89081 Ulm, Germany.
Joachim
J
Bischof
Institute of Pathophysiology and Process Development in Anesthesia, University of Ulm, Helmholtzstrasse 8/1, 89081 Ulm, Germany.
Peter
P
Radermacher
Divison of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, University of Ulm, Eythstrasse 24, 89075 Ulm, Germany.
Martin
M
Wabitsch
Department of General and Visceral Surgery, University of Ulm, Albert-Einstein-Allee 23, 89081 Ulm, Germany.
Doris
D
Henne-Bruns
Department of General and Visceral Surgery, University of Ulm, Albert-Einstein-Allee 23, 89081 Ulm, Germany.
Anna-Maria
AM
Wolf
Department of General and Visceral Surgery, University of Ulm, Albert-Einstein-Allee 23, 89081 Ulm, Germany.
Andreas
A
Hillenbrand
Department of General and Visceral Surgery, University of Ulm, Albert-Einstein-Allee 23, 89081 Ulm, Germany. Electronic address: uwe.knippschild@uniklinik-ulm.de.
Uwe
U
Knippschild
D017667:Adipocytes / Q000187:drug effects / Q000201:enzymology; D052242:Adiponectin / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D047389:Casein Kinase I / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D007211:Indoles; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009767:Obesity, Morbid / Q000201:enzymology* / Q000235:genetics*; D009852:Omentum / Q000201:enzymology; D010696:Phloroglucinol / Q000031:analogs & derivatives; D010766:Phosphorylation / Q000187:drug effects; D055503:Protein Multimerization / Q000187:drug effects; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D050151:Subcutaneous Fat / Q000201:enzymology*; D055815:Young Adult
C108123:4-amino-5-(4-methylphenyl)-7-(tert-butyl)pyrazolo(3,4-d)pyrimidine; C499918:ADIPOQ protein, human; D052242:Adiponectin; C411652:IC 261; D007211:Indoles; D007527:Isoenzymes; D011720:Pyrazoles; D011743:Pyrimidines; D010696:Phloroglucinol; D047389:Casein Kinase I
Adiponectin; CK1; Multimerization; Obesity; Phosphorylation