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  • Original Article
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Time-course microarrays reveal modulation of developmental, lipid metabolism and immune gene networks in intrascapular brown adipose tissue during the development of diet-induced obesity

International Journal of Obesity volume 37, pages 1524–1531 (2013)Cite this article

Subjects

Abstract

Objective:

The aim of this study was to establish the time-course of molecular events in intrascapular brown adipose tissue (iBAT) during the development of diet-induced obesity using microarrays and molecular network analysis.

Design:

C57BL/6J male inbred mice were fed a high-fat diet (HFD) or normal diet (ND) and killed at multiple time-points over 24 weeks.

Methods:

Global transcriptional changes in iBAT were determined by time-course microarrays of pooled RNA (n=6, pools per time-point) at 2, 4, 8, 20 and 24 weeks using Illumina MouseWG-6 v2.0 Beadchips. Molecular networks were constructed using the Ingenuity knowledgebase based on differentially expressed genes at each time-point.

Results:

Body weight and subcutaneous adipose were progressively increased over 24 weeks, whereas iBAT was significantly increased between 6 and 12 weeks in HFD-fed C57BL/6J mice compared with controls. Blood glucose and insulin levels were increased between 16 and 24 weeks. Time-course microarrays, revealed 155 differentially expressed genes at one or more time-points over 24 weeks in the iBAT of HFD-fed mice compared with controls. Time-course network analysis revealed a network of skeletal muscle development genes that was activated between 2 and 4 weeks, subsequently a network of immune trafficking genes was activated at 8 weeks. After 20 and 24 weeks, multiple lipid metabolism and immune response networks were activated. Several target genes identified by time-course microarrays were independently validated using RT-qPCR. Tnnc1 was upregulated early between 2 and 4 weeks, later Cd68 and Col1a1 were upregulated between 20 and 24 weeks, whereas 11β-hydroxysteroid dehydrogenase (Hsd11b1) was consistently downregulated during the development of diet-induced obesity.

Conclusion:

Molecular networks in iBAT are modulated in a time-dependent manner in response to a HFD. A broad range of gene targets exists to alter molecular changes within iBAT during the development of diet-induced obesity.

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Acknowledgements

This research was supported by the SRC program (Center for Food and Nutritional Genomics: grant number 2011-0000912) and the fundamental technology program (grant number 2012M3A9C4048818) of the National Research Foundation (NRF) of Korea funded by the Ministry of Education, Science and Technology.

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Authors and Affiliations

  1. Department of Food Science and Nutrition, Center for Food and Nutritional Genomics Research, Kyungpook National University, Daegu, Republic of Korea

    R A McGregor, E-Y Kwon, S-K Shin, U J Jung & M-S Choi

  2. Institute for Innovation in Biology, School of Biological Sciences, University of Auckland, Auckland, New Zealand

    R A McGregor

  3. Department of Food Science and Nutrition, Catholic University of Daegu, Gyeongsan, Republic of Korea

    E Kim

  4. Department of Food Science and Nutrition, College of Natural Sciences, Hallym University, Chuncheon, Republic of Korea

    J H Y Park

  5. Department of Food Science and Nutrition, University of Ulsan, Ulsan, Republic of Korea

    R Yu

  6. Department of Biotechnology, Daegu University, Kyungsan, Kyungbuk, Republic of Korea

    J W Yun

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McGregor, R., Kwon, EY., Shin, SK. et al. Time-course microarrays reveal modulation of developmental, lipid metabolism and immune gene networks in intrascapular brown adipose tissue during the development of diet-induced obesity. Int J Obes 37, 1524–1531 (2013). https://doi.org/10.1038/ijo.2013.52

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