Dual suppression of adipogenesis by cigarette smoke through activation of the aryl hydrocarbon receptor and induction of endoplasmic reticulum stress Export

@article{citeulike:4096710, abstract = {Cigarette smoking decreases body weight, whereas molecular mechanisms underlying this phenomenon have not been elucidated. In this report, we investigated regulation of adipogenesis by cigarette smoke and involvement of aryl hydrocarbon receptor (AhR) and endoplasmic reticulum (ER) stress. We found that cigarette smoke extract (CSE) inhibited differentiation of preadipocytes into adipocytes dose dependently. It was associated with a decrease in lipid accumulation, blunted expression of adipocyte markers (adiponectin, PPAR-{gamma}, and C/EBP{alpha}), and sustained expression of a preadipocyte marker MCP-1. CSE markedly induced activation of AhR, and AhR agonists (2,3,7,8-tetrachlorodibenzo-p-dioxin, benzo[a]pyrene and 3-methylcholanthrene) reproduced the inhibitory effect of CSE on adipocyte differentiation. Furthermore, knockout of the AhR gene or blockade of AhR by a dominant-negative mutant attenuated the suppressive effects of CSE on adipocyte differentiation. We also found that CSE induced ER stress in preadipocytes, and ER stress inducers (thapsigargin, tunicamycin, and A23187 ) reproduced the suppressive effect of CSE on the differentiation of preadipocytes. Interestingly, AhR agonists did not cause ER stress, and ER stress inducers did not activate AhR. These results suggested that cigarette smoke has the potential to inhibit adipocyte differentiation via dual, independent mechanisms, i.e., through activation of the AhR pathway and induction of the unfolded protein response. 10.1152/ajpendo.90829.2008}, author = {Shimada, Tsuyoshi and Hiramatsu, Nobuhiko and Hayakawa, Kunihiro and Takahashi, Shuhei and Kasai, Ayumi and Tagawa, Yasuhiro and Mukai, Mai and Yao, Jian and Fujii-Kuriyama, Yoshiaki and Kitamura, Masanori}, citeulike-article-id = {4096710}, citeulike-linkout-0 = {http://dx.doi.org/10.1152/ajpendo.90829.2008}, citeulike-linkout-1 = {http://ajpendo.physiology.org/cgi/content/abstract/296/4/E721?rss=1}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/19141685}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=19141685}, day = {1}, doi = {10.1152/ajpendo.90829.2008}, journal = {Am J Physiol Endocrinol Metab}, keywords = {adipogenesis, ahr, cigarette\_smoke, endoplasmic\_reticulum\_stress}, month = {April}, number = {4}, pages = {E721--730}, posted-at = {2009-02-25 07:40:02}, priority = {3}, title = {Dual suppression of adipogenesis by cigarette smoke through activation of the aryl hydrocarbon receptor and induction of endoplasmic reticulum stress}, url = {http://dx.doi.org/10.1152/ajpendo.90829.2008}, volume = {296}, year = {2009} }

TY - JOUR ID - citeulike:4096710 L3 - citeulike-article-id:4096710 N2 - Cigarette smoking decreases body weight, whereas molecular mechanisms underlying this phenomenon have not been elucidated. In this report, we investigated regulation of adipogenesis by cigarette smoke and involvement of aryl hydrocarbon receptor (AhR) and endoplasmic reticulum (ER) stress. We found that cigarette smoke extract (CSE) inhibited differentiation of preadipocytes into adipocytes dose dependently. It was associated with a decrease in lipid accumulation, blunted expression of adipocyte markers (adiponectin, PPAR-{gamma}, and C/EBP{alpha}), and sustained expression of a preadipocyte marker MCP-1. CSE markedly induced activation of AhR, and AhR agonists (2,3,7,8-tetrachlorodibenzo-p-dioxin, benzo[a]pyrene and 3-methylcholanthrene) reproduced the inhibitory effect of CSE on adipocyte differentiation. Furthermore, knockout of the AhR gene or blockade of AhR by a dominant-negative mutant attenuated the suppressive effects of CSE on adipocyte differentiation. We also found that CSE induced ER stress in preadipocytes, and ER stress inducers (thapsigargin, tunicamycin, and A23187 ) reproduced the suppressive effect of CSE on the differentiation of preadipocytes. Interestingly, AhR agonists did not cause ER stress, and ER stress inducers did not activate AhR. These results suggested that cigarette smoke has the potential to inhibit adipocyte differentiation via dual, independent mechanisms, i.e., through activation of the AhR pathway and induction of the unfolded protein response. 10.1152/ajpendo.90829.2008 IS - 4 JF - Am J Physiol Endocrinol Metab EP - 730 TI - Dual suppression of adipogenesis by cigarette smoke through activation of the aryl hydrocarbon receptor and induction of endoplasmic reticulum stress VL - 296 SP - E721 KW - adipogenesis KW - ahr KW - cigarette_smoke KW - endoplasmic_reticulum_stress AU - Shimada, Tsuyoshi AU - Hiramatsu, Nobuhiko AU - Hayakawa, Kunihiro AU - Takahashi, Shuhei AU - Kasai, Ayumi AU - Tagawa, Yasuhiro AU - Mukai, Mai AU - Yao, Jian AU - Fujii-Kuriyama, Yoshiaki AU - Kitamura, Masanori PY - 2009/04/01/ UR - http://dx.doi.org/10.1152/ajpendo.90829.2008 ER -