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Effect of estrogen on expression of prohibitin in white adipose tissue and liver of diet-induced obese rats

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Abstract

Prohibitin (PHB) is a ubiquitously expressed and highly conserved protein that participates in diverse cellular processes, and its functions are linked to a variety of diseases. In the present study, to explore transcriptional activation and signaling pathways involved in PHB regulation in response to sex hormone treatment, we investigated the effects of estrogen (17-β-estradiol, E2) on regulation of PHB in several metabolic tissues from male and female rats. Elevated expression of PHB was prominent in white adipose tissue (WAT) and the liver, and E2 stimulated PHB expression in both ND and HFD-fed rats. To further confirm the expression of PHB which was increased in WAT and the liver, we analyzed PHB expression levels in 3T3-L1 and C9 cells after the treatment of E2. Transcription and protein levels of PHB were dose-dependently increased by E2 treatment in both cell types, supporting our in vivo data. To further evaluate the possible role of E2 in elevation of PHB via estrogen receptors (ER), the potent ER inhibitor fulvestrant was treated to 3T3-L1 and C9 cells. Fulvestrant markedly suppressed both transcription and protein levels of PHB, suggesting that PHB expression in both tissues may be regulated through ERs. GeneMANIA, a predictive web interface, was used to show that Phb is regulated via the intracellular steroid hormone receptor signaling pathway, suggesting a role for ERs in expression of Phb as well as other metabolically important genes. Based on these results, we expect that targeting PHB would be a useful therapeutic approach for treatment of obesity.

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Abbreviations

ANXA2/Anxa2 :

Annexin A2/-encoding gene

ARL4A/Arl4a :

ADP-ribosylation factor-like protein 4A/-encoding gene

AR:

Androgen receptor

BAT:

Brown adipose tissue

CON:

Control

ER:

Estrogen receptor

E2:

17-β-Estradiol

Esr1 :

Estrogen receptor α-encoding gene

Esr2 :

Estrogen receptor β-encoding gene

LP3/Gzmb :

Granzyme-like protein 3/-encoding gene

HFD:

High fat diet

IL17RB/Il17rb :

Interleukin-17 receptor B/-encoding gene

MATK/Matk :

Megakaryocyte-associated tyrosine kinase/-encoding gene

ND:

Normal diet

PHB/Phb :

Prohibitin/-encoding gene

PHB2/Phb2 :

Prohibitin 2/-encoding gene

USP15/Usp15 :

Ubiquitin carboxyl-terminal hydrolase 15/-encoding gene

WAT:

White adipose tissue

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Acknowledgments

This work was supported by the Mid-career Researcher Program (2013R1A2A2A05004195) and SRC Program (Center for Food and Nutritional Genomics, Grant number 2015R1A5A6001906) through NRF Grant funded by the Ministry of Science, ICT and Future Planning, Korea.

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    Authors and Affiliations

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

      Minji Choi, Harmesh N. Chaudhari, Sang Woo Kim & Jong Won Yun

    2. School of Life Science and Biotechnology, Kyungpook National University, Daegu, 702-701, Republic of Korea

      Young Rae Ji & Zae Young Ryoo

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    1. Minji Choi
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    Correspondence to Jong Won Yun.

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    Minji Choi and Harmesh N. Chaudhari have contributed equally to this work.

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    Choi, M., Chaudhari, H.N., Ji, Y.R. et al. Effect of estrogen on expression of prohibitin in white adipose tissue and liver of diet-induced obese rats. Mol Cell Biochem 407, 181–196 (2015). https://doi.org/10.1007/s11010-015-2468-1

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