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Nutrient-Gene Interactions

Gene Expression Profiling in Human Preadipocytes and Adipocytes by Microarray Analysis^1,2

Sumithra Urs^*, Colton Smith, Brett Campbell^*, Arnold M. Saxton^**, James Taylor, Bing Zhang, Jay Snoddy^,, Brynn Jones Voy^*,, and Naima Moustaid-Moussa^*,,3

^* Department of Nutrition, Web Services, and ^** Animal Science, The University of Tennessee, Knoxville, TN 37996-1920; Plastic Surgery, The University of Tennessee Medical Center, Knoxville, TN; University of Tennessee-Oak Ridge National Laboratory Graduate School in Genome Science and Technology, Oak Ridge, TN; and Oak Ridge National Laboratory, Oak Ridge, TN

³To whom correspondence should be addressed. E-mail: moustaid{at}utk.edu.

Uncontrolled expansion of adipose tissue leads to obesity, a public health epidemic affecting >30% of adult Americans. Adipose mass increases in part through the recruitment and differentiation of an existing pool of preadipocytes (PA) into adipocytes (AD). Most studies investigating adipogenesis used primarily murine cell lines; much less is known about the relevant processes that occur in humans. Therefore, characterization of genes associated with adipocyte development is key to understanding the pathogenesis of obesity and developing treatments for this disorder. To address this issue, we performed large-scale analyses of human adipose gene expression using microarray technology. Differential gene expression between PA and AD was analyzed in 6 female patients using human cDNA microarray slides and data analyzed using the Stanford Microarray Database. Statistical analysis for the gene expression was performed using the SAS mixed models. Compared with PA, several genes involved in lipid metabolism were overexpressed in AD, including fatty acid binding protein, adipose differentiation-related protein, lipoprotein lipase, perilipin, and adipose most abundant transcript 1. Novel genes expressed in adipocytes included E2F5 transcriptional factor and SMARC (SWI/SNF-related, matrix associated, actin-dependent regulator of chromatin). PA predominantly expressed genes encoding extracellular matrix components such as fibronectin, matrix metalloprotein, and novel proteins such as lysyl oxidase. Despite the high differential expression of some of these genes, many did not differ significantly likely due to high variability and limited statistical power. A comprehensive list of differential gene expression is presented according to cellular function. In conclusion, these studies offer an overview of the gene expression profiles in PA and AD and identify new genes with potentially important functions in adipose tissue development and obesity that merit further investigation.

KEY WORDS: • microarray • adipose tissue • gene profiling • reverse transcriptase-polymerase chain reaction

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