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Bromocriptine inhibits adipogenesis and lipogenesis by agonistic action on α2-adrenergic receptor in 3T3-L1 adipocyte cells

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Abstract

The primary goals of the present study were to investigate the inhibitory effects of bromocriptine (BC) on adipogenesis and lipogenesis in 3T3-L1 adipocyte cells as well as to elucidate its molecular mechanism of action. Adipogenic and lipogenic capacity of BC-treated cells was evaluated by oil red-O staining, triglyceride content assay, real-time RT-PCR and immunoblotting. To determine the mechanism responsible for the anti-obesity effect of BC, we applied two methods. Firstly, we knocked down dopamine D2 receptor (D2R) up to 50 % using siRNA. Secondly, we blocked the activity of α2-adrenergic receptor (α2-AR) by yohimbine treatment and monitored its effects on adipogenic and lipogenic events in 3T3-L1 cells. BC decreased the expression levels of adipogenic activators, including Pparα, Pparγ, and Cebpα, as well as major lipogenic target genes, including Me1, Acc1, 6Pgd, Fasn, and Prkaa1. Moreover, BC markedly reduced intracellular nitric oxide formation in a dose-dependent manner and expression of pro-inflammatory genes, Tnfα and Il6, which reflects attenuated pro-inflammatory responses. Further, upon treatment with BC, D2R-deficient cells displayed a significant decrease in lipogenic activity compared to control cells, whereas yohimbine-treated cells exhibited no reduction in lipogenic activity. BC can effectively attenuate adipogenesis and lipogenesis in 3T3-L1 cells by downregulating the expression of lipogenic genes and proteins. Our current experimental data collectively establish that the anti-obesity effects of BC are not D2R-dependent but result from the action of α2-AR in 3T3-L1 adipocytes.

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Abbreviations

ACC:

Acyl CoA carboxylase

AMPK (Prka):

AMP-activated protein kinase (encoded gene)

AR:

Adrenergic receptor

BC:

Bromocriptine

C/ebp :

Gene encoding CCAAT/enhancer-binding protein

DR:

Dopamine receptor

FAS (Fasn):

Fatty acid synthase (encoded gene)

KD:

Knockdown

Lep:

Leptin

Il :

Gene encoding interleukin

Me:

Malic enzyme

NO:

Nitric oxide

Pgd :

Gene encoding phosphogluconate dehydrogenase

PPAR:

Peroxisome proliferator-activated receptor

siRNA:

Small interference RNA

Tnf :

Gene encoding tumor necrosis factor

YB:

yohimbine

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Acknowledgments

This work was supported by a Daegu University Research Grant 2012.

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  1. Department of Biotechnology, Daegu University, Kyungsan, Kyungbuk, 712-714, Republic of Korea

    Rajib Mukherjee & Jong Won Yun

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  1. Rajib Mukherjee
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Correspondence to Jong Won Yun.

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Mukherjee, R., Yun, J.W. Bromocriptine inhibits adipogenesis and lipogenesis by agonistic action on α2-adrenergic receptor in 3T3-L1 adipocyte cells. Mol Biol Rep 40, 3783–3792 (2013). https://doi.org/10.1007/s11033-012-2455-5

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