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Alteration of mitochondria during adipocyte differentiation and mitochondrial dysfunction leads to insulin resistance of adipocytes
Author(s) -
Wang ChihHao,
Wei YauHuei
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1226.40
Subject(s) - adipogenesis , insulin resistance , tfam , mitochondrial biogenesis , adipocyte , mitochondrion , endocrinology , medicine , biology , downregulation and upregulation , oligomycin , nrf1 , insulin , microbiology and biotechnology , adipose tissue , biochemistry , enzyme , gene , atpase
Adipocytes play an important role in the regulation of energy metabolism and maintenance of glucose homeostasis in the human body. Recent studies showed that mitochondrial dysfunction is involved in metabolic diseases, such as insulin resistance and type II diabetes. Here, we investigated the importance of mitochondria in the differentiation and function of adipocytes. We used 3T3‐L1 fibroblasts as a model of adipocyte differentiation. First, we examined the changes of mitochondrial biogenesis during adipogenesis. The results showed that mitochondrial biogenesis‐related genes, including PGC‐1α and mtTFA, were up‐regulated during adipogenesis. Besides, we observed that mitochondrial DNA content and the subunits of respiratory enzyme complexes were slightly increased after differentiation. To further investigate the role of mitochondrial dysfunction in insulin resistance and type II diabetes, we treated adipocytes with respiratory inhibitors, oligomycin and antimycin A, respectively. The results showed that mitochondrial dysfunction led to a significant decrease in the sensitivity of the adipocytes to insulin as revealed by a dramatic decrease in Akt phosphorylation. Taken these findings together, we suggest that upregulation of mitochondrial biogenesis plays an important role in the differentiation of adipocytes to execute aerobic metabolism to maintain their normal physiological functions. On the other hand, we demonstrated that mitochondrial dysfunction can lead to insulin resistance of adipocytes in vitro.