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. 2010 Jun 9;5(6):e11033.
doi: 10.1371/journal.pone.0011033.

Switch from stress response to homeobox transcription factors in adipose tissue after profound fat loss

Simon N Dankel  1 , Dag J Fadnes, Anne-Kristin Stavrum, Christine Stansberg, Rita Holdhus, Tuyen Hoang, Vivian L Veum, Bjørn Jostein Christensen, Villy Våge, Jørn V Sagen, Vidar M Steen, Gunnar Mellgren
Affiliations

V体育安卓版 - Switch from stress response to homeobox transcription factors in adipose tissue after profound fat loss

Simon N Dankel et al. PLoS One. .

Abstract (VSports手机版)

Background: In obesity, impaired adipose tissue function may promote secondary disease through ectopic lipid accumulation and excess release of adipokines, resulting in systemic low-grade inflammation, insulin resistance and organ dysfunction. However, several of the genes regulating adipose tissue function in obesity are yet to be identified. VSports手机版.

Methodology/principal findings: In order to identify novel candidate genes that may regulate adipose tissue function, we analyzed global gene expression in abdominal subcutaneous adipose tissue before and one year after bariatric surgery (biliopancreatic diversion with duodenal switch, BPD/DS) (n = 16). Adipose tissue from lean healthy individuals was also analyzed (n = 13) V体育安卓版. Two different microarray platforms (AB 1700 and Illumina) were used to measure the differential gene expression, and the results were further validated by qPCR. Surgery reduced BMI from 53. 3 to 33. 1 kg/m(2). The majority of differentially expressed genes were down-regulated after profound fat loss, including transcription factors involved in stress response, inflammation, and immune cell function (e. g. , FOS, JUN, ETS, C/EBPB, C/EBPD). Interestingly, a distinct set of genes was up-regulated after fat loss, including homeobox transcription factors (IRX3, IRX5, HOXA5, HOXA9, HOXB5, HOXC6, EMX2, PRRX1) and extracellular matrix structural proteins (COL1A1, COL1A2, COL3A1, COL5A1, COL6A3). .

Conclusions/significance: The data demonstrate a marked switch of transcription factors in adipose tissue after profound fat loss, providing new molecular insight into a dichotomy between stress response and metabolically favorable tissue development. Our findings implicate homeobox transcription factors as important regulators of adipose tissue function. V体育ios版.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Correspondence Analysis showing projection of samples before and after bariatric surgery and lean healthy controls.
The first principal component (10.69% component variance) separated the pre-operative samples from the post-operative and control samples, and the second principal component (6.36% component variance) separated the post-operative from control samples. The post-operative sample of patient 17 was similar to the pre-operative samples, suggesting an overall unaltered gene expression pattern after surgery for this patient. A technical error may have occurred, but we cannot rule out a unique gene expression pattern in the adipose tissue of this patient.
Figure 2
Figure 2. Functional categorization of differentially expressed genes in subcutaneous adipose tissue after fat loss (Biological Process).
PANTHER was used to search for over-represented Biological Process categories among the most differentially expressed genes (q-value = 0, fold change ≥1.5), comparing adipose tissue before versus after bariatric surgery (n = 16) and versus controls (n = 13). The color intensity displays the statistical significance (−log p-value) of over- and under-represented PANTHER functional categories. A p-value<0.01 with Bonferroni correction for multiple testing was used as inclusion criterion for categories. Numbers presented in the table indicate the percentage of genes within a gene set that map to the given category, e.g. 18% of the 469 down-regulated genes map to the biological process ‘Immunity and defense’. The first column states the overall distribution of a term among all human NCBI genes (25,431), e.g. 5% of the genes are expected to map to ‘Immunity and defense’, hence this category is significantly over-represented among the down-regulated genes. Ref, reference (based on all human NCBI genes); Pre, pre-surgery biopsies; Post, post-surgery biopsies; Ctr, biopsies of lean controls; Arrow up, up-regulated/more expressed genes; Arrow down, down-regulated/less expressed genes.
Figure 3
Figure 3. Functional categorization of differentially expressed genes in subcutaneous adipose tissue after fat loss (Molecular Function).
PANTHER was used to search for over-represented Molecular Function categories among the most differentially expressed genes (q-value = 0, fold change ≥1.5), comparing adipose tissue before versus after bariatric surgery (n = 16) and versus controls (n = 13). The color intensity displays the statistical significance (−log p-value) of over- and under-represented PANTHER functional categories. A p-value<0.01 with Bonferroni correction for multiple testing was used as inclusion criterion for categories. Numbers presented in the table indicate the percentage of genes within a gene set that map to the given category, e.g. 8% of the 469 down-regulated genes map to the molecular function ‘Signalling molecule’. The first column states the overall distribution of a term among all human NCBI genes (25,431), e.g. 3% of the genes are expected to map to ‘Signalling molecule’, hence this category is significantly over-represented among the down-regulated genes. Ref, reference (based on all human NCBI genes); Pre, pre-surgery biopsies; Post, post-surgery biopsies; Ctr, biopsies of lean controls; Arrow up, up-regulated/more expressed genes; Arrow down, down-regulated/less expressed genes.
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