Gene expression profiling of subcutaneous adipose tissue in morbid obesity using a focused microarray: Distinct expression of cell-cycle- and differentiation-related genes

Abstract

BackgroundObesity results from an imbalance between food intake and energy expenditure, which leads to an excess of adipose tissue. The excess of adipose tissue and adipocyte dysfunction associated with obesity are linked to the abnormal regulation of adipogenesis. The objective of this study was to analyze the expression profile of cell-cycle- and lipid-metabolism-related genes of adipose tissue in morbid obesity.MethodsWe used a custom-made focused cDNA microarray to determine the adipose tissue mRNA expression profile. Gene expression of subcutaneous abdominal fat samples from 15 morbidly obese women was compared with subcutaneous fat samples from 10 nonobese control patients. The findings were validated in an independent population of 31 obese women and 9 obese men and in an animal model of obesity (Lepob/ob mice) by real-time RT-PCR.ResultsMicroarray analysis revealed that transcription factors that regulate the first stages of adipocyte differentiation, such as CCAAT/enhancer binding protein beta (C/EBPβ) and JUN, were upregulated in the adipose tissues of morbidly obese patients. The expression of peroxisome proliferator-activated receptor gamma (PPARγ), a transcription factor which controls lipid metabolism and the final steps of preadipocyte conversion into mature adipocytes, was downregulated. The expression of three cyclin-dependent kinase inhibitors that regulate clonal expansion and postmitotic growth arrest during adipocyte differentiation was also altered in obese subjects: p18 and p27 were downregulated, and p21 was upregulated. Angiopoietin-like 4 (ANGPTL4), which regulates angiogenesis, lipid and glucose metabolism and it is know to increase dramatically in the early stages of adipocyte differentiation, was upregulated. The expression of C/EBPβ, p18, p21, JUN, and ANGPTL4 presented similar alterations in subcutaneous adipose tissue of Lepob/ob mice.ConclusionsOur microarray gene profiling study revealed that the expression of genes involved in adipogenesis is profoundly altered in the subcutaneous adipose tissue of morbidly obese subjects. This expression pattern is consistent with an immature adipocyte phenotype that could reflect the expansion of the adipose tissue during obesity.

Restoration of adipose function in obese glucose-tolerant men following pioglitazone treatment is associated with CCAAT enhancer-binding protein β up-regulation

“…NR_003286; forward 5 -CGGAGGTT-CGAAGACGATCA-3 ; reverse 5 -GGCATCGTTT-ATGGTCGGAA-3 ). These housekeeping genes have been used in previous gene expression analyses in AT and, in agreement with previous studies [19][20][21], in the present study expression of none of the three housekeeping genes were found to be altered by either obesity or treatment. Individual subject gene expression was normalized to the relevant housekeeping gene ( C t ).…”

Expression Levels of Obesity-Related Genes Are Associated with Weight Change in Kidney Transplant Recipients

“…To date, a few studies have examined cross-sectional gene expression levels in adipose tissue of obese and non-obese subjects. These studies have identified genes related to adipogenesis [19], as well as glucose and insulin regulation pathways and inflammatory responses [6]. In our longitudinal study, gene expression was examined at baseline and correlated with weight change at 6 months post-transplantation.…”

Determinants of Human Adipose Tissue Gene Expression: Impact of Diet, Sex, Metabolic Status, and Cis Genetic Regulation

“…However, 80% of the genes remained different when controlling for fat mass. Indeed, SAA4 and CDKN2C AT expression are increased and decreased, respectively, in morbidly obese subjects whereas the two genes show higher expression in women than men [25], [26]. The contribution of gonadal hormones and sex chromosomes has been investigated in mouse models.…”