Adiponectin improves clozapine-induced lipid accumulation and inflammation without affecting insulin resistance
| Autor: | 蔡宜倫 |
|---|---|
| Rok vydání: | 2011 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 99 Atypical antipsychotic drugs (AAPDs) may cause side effects including weight gain, diabetes, and other cardiovascular diseases such as fatty liver. Clozapine-induced weight gain is most significant in cases of AAPDs. Our previous data showed that clozapine could inhibit adiponectin secretion in mouse 3T3L1 adipocytes. Adiponectin, a cytokine secreted by adipocytes, can act on hepatocyte by means of paracrine. Adiponectin has anti-inflammation and insulin-sensitizing properties. We have demonstrated that clozapine could induce liver inflammation and insulin resistance in hepatocyte. In this study, we sought to elucidate whether clozapine could cause lipid accumulation as well as whether adiponectin would inhibit clozapine-induced inflammation and insulin resistance in human hepatocyte. Lipid was first labeled with fluorescent dye and its accumulation was analyzed by flow cytometry. This result indicated a time-dependent lipid accumulation in clozapine-treated HepG2 cells. The level of fatty acid synthase (FASN) of lipogenesis pathway was also increased. We investigated adipoR1 and adipoR2 mRNA expression by real-time PCR, and both adipoR1 and adipoR2 mRNA expressions were inhibited by clozapine. In addition, adiponectin indeed inhibited lipid accumulation when adiponectin was overexpressed in HepG2 cells. Moreover, the result showed that adiponectin significantly improved the inflammation induced by NF-κB but exerted no effect on insulin resistance induced by clozapine. In the future, we will further investigate the inability of adiponectin to improve insulin resistance induced by clozapine. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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