Changes in the transcriptome of abdominal subcutaneous adipose tissue in response to short-term overfeeding in lean and obese men.
BACKGROUND
Obesity is caused by the excessive accumulation of adipose tissue as a result of a chronic energy surplus. Little is known regarding the molecular mechanisms involved in the response to an energy surplus in human adipose tissue at the genomic level.


OBJECTIVE
The objective was to investigate changes in the transcriptome of abdominal subcutaneous adipose tissue after a positive energy challenge induced by overfeeding in both lean and obese subjects to identify novel obesity candidate genes.


METHODS
A total of 26 men were recruited and classified on the basis of percentage body fat (measured by dual-energy X-ray absorptiometry) as lean (<20%) or obese (>25%) to participate in the baseline comparison. Sixteen men participated in the overfeeding study (8 lean and 8 obese). Adipose tissue biopsy samples were collected from all subjects at the subumbilical region. Global gene expression profiles were determined at baseline and after a 7-d hypercaloric diet at 40% above normal energy requirements by using whole human genome DNA microarrays.


RESULTS
Overfeeding induced differential expression in 45 genes. Six genes displayed a significant interaction effect between adiposity status and overfeeding treatment, including transferrin (TF), stearoyl-CoA desaturase (SCD), transaldolase 1 (TALDO1), cathepsin C (CTSC), insulin receptor substrate 2 (IRS2), and pyruvate dehydrogenase kinase, isozyme 4 (PDK4). Overfeeding resulted in changes in expression of these genes in lean subjects, whereas no significant changes were evident in obese subjects.


CONCLUSIONS
Differential expression of these 6 genes may represent a protective mechanism at the molecular level in lean subjects in response to an energy surplus. These genes represent valuable candidates for downstream studies related to obesity.
Shea
Jennifer
J
Discipline of Genetics and Medicine, Faculty of Medicine, Memorial University of Newfoundland, St John's, NL, Canada.
French
Curtis R
CR
Bishop
Jessica
J
Martin
Glynn
G
Roebothan
Barbara
B
Pace
David
D
Fitzpatrick
Donald
D
Sun
Guang
G
D000328:Adult; D001823:Body Composition / Q000502:physiology; D002149:Energy Intake / Q000502:physiology*; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D008297:Male; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050507:Subcutaneous Fat, Abdominal / Q000378:metabolism*; D013851:Thinness / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult