Bauer, Sabrina and Wanninger, Josef and Schmidhofer, Sandra and Weigert, Johanna and Neumeier, Markus and Dorn, Christoph and Hellerbrand, Claus and Zimara, Nicole and Schaeffler, Andreas and Aslanidis, Charalampos and Buechler, Christa (2011) Sterol Regulatory Element-Binding Protein 2 (SREBP2) Activation after Excess Triglyceride Storage Induces Chemerin in Hypertrophic Adipocytes. ENDOCRINOLOGY, 152 (1). pp. 26-35. ISSN 0013-7227, 1945-7170
Full text not available from this repository. (Request a copy)Abstract
Chemerin is an adipokine whose systemic concentration and adipose tissue expression is increased in obesity. Chemerin is highly abundant in adipocytes, yet the molecular mechanisms mediating its further induction in obesity have not been clarified. Adipocyte hypertrophy contributes to dys-regulated adipokine synthesis, and we hypothesized that excess loading with free fatty acids (FFA) stimulates chemerin synthesis. Chemerin was expressed in mature adipocytes, and differentiation of 3T3-L1 cells in the presence of FFA further increased its level. TNF and IL-6 were induced by FFA, but concentrations were too low to up-regulate chemerin. Sterol regulatory element-binding protein 2 (SREBP2) was activated in these cells, indicative for cholesterol shortage. Suppression of cholesterol synthesis by lovastatin led to activation of SREBP2 and increased chemerin, and supplementation with mevalonate reversed this effect. Knockdown of SREBP2 reduced basal and FFA-induced chemerin. EMSA confirmed binding of 3T3-L1 adipocyte nuclear proteins to a SREBP site in the chemerin promotor. SREBP2 was activated and chemerin was induced in adipose tissue of mice fed a high-fat diet, and higher systemic levels seem to be derived from adipocytes. Lipopolysaccharide-mediated elevation of chemerin was similarly effective as induction by FFA, indicating that both mechanisms are equally important. Chemokine-like receptor 1 was not altered by the incubations mentioned above, and higher expression in fat of mice fed a high-fat diet may reflect increased number of adipose tissue-resident macrophages in obesity. In conclusion, the current data show that adipocyte hypertrophy and chronic inflammation are equally important in inducing chemerin synthesis. (Endocrinology 152: 26-35, 2011)
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ADIPOSE-TISSUE; INSULIN-RESISTANCE; METABOLIC SYNDROME; 3T3-L1 ADIPOCYTES; GENE-EXPRESSION; TNF-ALPHA; FATTY-ACIDS; OBESITY; ADIPOKINE; ADIPOGENESIS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 29 Jun 2020 11:59 |
| Last Modified: | 29 Jun 2020 11:59 |
| URI: | https://pred.uni-regensburg.de/id/eprint/21566 |
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