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Open Access Research article

Time-course microarrays reveal early activation of the immune transcriptome and adipokine dysregulation leads to fibrosis in visceral adipose depots during diet-induced obesity

Eun-Young Kwon1, Su-Kyung Shin1, Yun-Young Cho1, Un Ju Jung1, Eunjung Kim2, Taesun Park3, Jung Han Yoon Park4, Jong Won Yun5, Robin A McGregor1, Yong Bok Park6 and Myung-Sook Choi17*

Author affiliations

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

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

3 Department of Food and Nutrition, Yonsei University, Seoul, Republic of Korea

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

5 Department of Biotechnology, Daegu University, Kyungsan, Kyungbuk, Republic of Korea

6 School of Life Science & Biotechnology, Kyungpook National University, Daegu, Republic of Korea

7 Department of Food Science and Nutrition, Kyungpook National University, 1370 Sank-Yuk Dong Puk-Ku, Daegu, 702-701, Korea

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Citation and License

BMC Genomics 2012, 13:450  doi:10.1186/1471-2164-13-450

Published: 4 September 2012

Abstract

Background

Visceral white adipose tissue (WAT) hypertrophy, adipokine production, inflammation and fibrosis are strongly associated with obesity, but the time-course of these changes in-vivo are not fully understood. Therefore, the aim of this study was to establish the time-course of changes in adipocyte morphology, adipokines and the global transcriptional landscape in visceral WAT during the development of diet-induced obesity.

Results

C57BL/6 J mice were fed a high-fat diet (HFD) or normal diet (ND) and sacrificed at 8 time-points over 24 weeks. Excessive fat accumulation was evident in visceral WAT depots (Epidydimal, Perirenal, Retroperitoneum, Mesentery) after 2–4 weeks. Fibrillar collagen accumulation was evident in epidydimal adipocytes at 24 weeks. Plasma adipokines, leptin, resistin and adipsin, increased early and time-dependently, while adiponectin decreased late after 20 weeks. Only plasma leptin and adiponectin levels were associated with their respective mRNA levels in visceral WAT. Time-course microarrays revealed early and sustained activation of the immune transcriptome in epididymal and mesenteric depots. Up-regulated inflammatory genes included pro-inflammatory cytokines, chemokines (Tnf, Il1rn, Saa3, Emr1, Adam8, Itgam, Ccl2, 3, 4, 6, 7 and 9) and their upstream signalling pathway genes (multiple Toll-like receptors, Irf5 and Cd14). Early changes also occurred in fibrosis, extracellular matrix, collagen and cathepsin related-genes, but histological fibrosis was only visible in the later stages.

Conclusions

In diet-induced obesity, early activation of TLR-mediated inflammatory signalling cascades by CD antigen genes, leads to increased expression of pro-inflammatory cytokines and chemokines, resulting in chronic low-grade inflammation. Early changes in collagen genes may trigger the accumulation of ECM components, promoting fibrosis in the later stages of diet-induced obesity. New therapeutic approaches targeting visceral adipose tissue genes altered early by HFD feeding may help ameliorate the deleterious effects of diet-induced obesity.

Keywords:
Adipocytokine dysregulation; Transcriptional response; Adipose tissue; Extracellular matrix; Cathepsin; Fibrosis