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Increased expression of FGF1-mediated signaling molecules in adipose tissue of obese mice

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Abstract

Fibroblast growth factors (FGFs) are pleiotropic growth factors that control cell proliferation, migration, and differentiation. Herein, we evaluated whether visceral adiposity of mice is accompanied by the alteration of signaling molecules mediated by fibroblast growth factor receptor 1 (FGFR1) induced by using two different male C57BL/6J mice models of obesity namely high-fat diet (HFD)-induced obesity for 12 weeks or mice with genetic deletion of leptin (ob/ob). Both HFD-fed and ob/ob mice exhibited significantly higher messenger RNA (mRNA) levels of FGF1, cyclin D (cycD), transcription factor E2F1, peroxisome proliferator-activated receptor-gamma 2 (PPAR-γ2), CCAAT-enhancer-binding protein alpha (C/EBPα), and adipocyte protein 2 (aP2) genes in their epididymal adipose tissues compared to those of the normal diet (ND)-fed and lean control mice, respectively. In addition, immunoblot analyses of the epididymal adipose tissues revealed that both mice exposed to HFD and ob/ob mice exhibited elevated phosphorylation of FGFR1, extracellular-signal-regulated kinase (ERK), and retinoblastoma (Rb) proteins. These data support the notion that FGF1-mediated signaling represents an important signaling cascade related to adipogenesis, at least partially, among other known signaling pathways. These new findings regarding the molecular mechanisms controlling adipose tissue plasticity provide a novel insight about the functional network with potential therapeutic application against obesity.

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Abbreviations

aP2:

Adipocyte protein 2

BMPs:

Bone morphogenetic proteins

C/EBPα:

CCAAT-enhancer-binding protein alpha

cycD:

Cyclin D

ERK:

Extracellular-signal-regulated kinase

FAS:

Fatty acid synthase

FGFs:

Fibroblast growth factors

FGFR1:

Fibroblast growth factor receptor 1

GSK3:

Glycogen synthase kinase 3

HFD:

High-fat diet

LPL:

Lipoprotein lipase

MVECs:

Microvascular endothelial cells

ND:

Normal diet

PPAR-γ2:

Peroxisome proliferator-activated receptor-gamma 2

Rb:

Retinoblastoma

Shn-2:

Schnurri-2

SMAD3:

Mothers against decapentaplegic homolog 3

SREBP-1c:

Sterol regulatory element-binding transcription factor 1c

TGF-β:

Transforming growth factor-beta

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Acknowledgments

This research was supported by Technology Commercialization Support Program (Program no. 1130373), Ministry of Agriculture, Food and Rural Affairs, and SRC program (Center for Food & Nutritional Genomics: Grant no. 2015R1A5A6001906) of the National Research Foundation of Korea funded by the Ministry of Education, Science, and Technology.

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Authors and Affiliations

  1. Department of Food and Nutrition, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-749, Republic of Korea

    Youngshim Choi, Suhyeon Jang & Taesun Park

  2. Department of Food Science and Nutrition, Kyungpook National University, 1370 Sankyuk-dong, Daegu, 702-701, Republic of Korea

    Myung-Sook Choi

  3. School of Life Science and Biotechnology, Kyungpook National University, 1370 Sankyuk-dong, Buk-ku, Daegu, 702-701, Republic of Korea

    Zae Young Ryoo

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  1. Youngshim Choi
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Correspondence to Taesun Park.

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Ethics statement

All animal experiments were performed humanely according to Korean Food and Drug Administration (KFDA) guidelines. All mouse experiments were approved by the Institutional Animal Care and Use Committee (IACUC) of the Yonsei Laboratory Animal Research Center (YLARC) (Permit no.: 2011-0061). All mice were maintained in the specific pathogen-free facility of the YLARC.

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The authors declare that they have no competing interests.

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Supplementary Table 1

Composition of the experimental diet (g/kg) fed to mice. (DOCX 13 kb)

Supplementary Table 2

Primer sequences used for semi-quantitative RT-PCR analysis. (DOC 37 kb)

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Choi, Y., Jang, S., Choi, MS. et al. Increased expression of FGF1-mediated signaling molecules in adipose tissue of obese mice. J Physiol Biochem 72, 157–167 (2016). https://doi.org/10.1007/s13105-016-0468-6

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  • DOI: https://doi.org/10.1007/s13105-016-0468-6

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