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


RESULTS
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). 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
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.
Dankel
Simon N
SN
Institute of Medicine, University of Bergen, Bergen, Norway.
Fadnes
Dag J
DJ
Stavrum
Anne-Kristin
AK
Stansberg
Christine
C
Holdhus
Rita
R
Hoang
Tuyen
T
Veum
Vivian L
VL
Christensen
Bjørn Jostein
BJ
Våge
Villy
V
Sagen
Jørn V
JV
Steen
Vidar M
VM
Mellgren
Gunnar
G
D000273:Adipose Tissue / Q000378:metabolism*; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000378:metabolism*; D015431:Weight Loss
D018398:Homeodomain Proteins; D014157:Transcription Factors