Clenbuterol inhibits SREBP-1c expression by activating CREB1.
As a beta(2)-adrenergic agonist, clenbuterol decreases body fat, but the molecular mechanism underlying this process is unclear. In the present study, we treated 293T and L-02 cells with clenbuterol and found that clenbuterol downregulates SREBP-1c expression and upregulates CREB1 expression. Considering SREBP-1c has the function of regulating the transcription of several lipogenic enzymes, we considered that the downregulation of SREBP-1c is responsible for body fat reduction by clenbuterol. Many previous studies have found that clenbuterol markedly increases intracellular cAMP levels, therefore, we also investigated whether CREB1 is involved in this process. The data from our experiments indicate that CREB1 overexpression inhibits SREBP-1c transcription, and that this action is antagonized by CREB2, a competitive inhibitor of CREB1. Furthermore, since PPARs are able to repress SREBP-1c transcription, we investigated whether clenbuterol and CREB1 function via a pathway involving PPAR activation. However, our results showed that clenbuterol or CREB1 overexpression suppressed PPARs transcription in 293T and L-02 cells, which suggested that they impair SREBP-1c expression in other ways.
Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, 430070, P. R. China.
Lei
L
Zhou
Yixing
Y
Li
Tao
T
Nie
Shengqiu
S
Feng
Jihong
J
Yuan
Huaping
H
Chen
Zaiqing
Z
Yang
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D002460:Cell Line; D002976:Clenbuterol / Q000494:pharmacology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
D000318:Adrenergic beta-Agonists; C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D007328:Insulin; D047492:Peroxisome Proliferator-Activated Receptors; D051780:Sterol Regulatory Element Binding Protein 1; D005947:Glucose; D002976:Clenbuterol