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Needle and surgical biopsy techniques differentially affect adipose tissue gene expression profiles^1,2,3

¹ From the INSERM, Nutriomique U872 Team 7, Paris, France (DMM, JT, VP, BH, CH, CP, J-DZ, and KC); the Université Pierre et Marie Curie Paris 6, Centre de Recherche des Cordeliers, Paris, France (DMM, JT, VP, BH, CH, CP, J-DZ, and KC); the Université Paris Descartes, Paris, France (DMM, JT, VP, BH, CH, CP, Z-DZ, and KC); the Assistance Publique-Hopitaux de Paris, Nutrition and Endocrinology Department, Pitié-Salpêtrière Hospital, Paris, France (CP and KC); and the Université Paris Descartes, Surgery Department, Hôtel-Dieu Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France (NV).

² Supported by Paris 6 University (Bonus Quality Research) and by the Assistance Publique Hôpitaux de Paris/Direction de la Recherche Clinique (CRC P050318), and a grant from the European Community 7th framework program: ADAPT "Adipokines as Drug Targets to combat Adverse effects of excess ADipose Tissue" project (grant agreement 201100). DMM is funded by the European Community [DiOGenes – Diet, genes and obesity (contract FP6-513946)].

³ Reprints not available. Address correspondence to DM Mutch, University of Guelph, Department of Human Health and Nutritional Sciences, Guelph, ON, Canada N1G 2W1. E-mail: dmutch{at}uoguelph.ca or dmmutch_sci{at}hotmail.com.

Background: Adipose tissue gene expression analysis in humans now provides a tremendous means to discover the physiopathologic gene targets critical for our understanding and treatment of obesity. Clinical studies are emerging in which adipose gene expression has been examined in hundreds of subjects, and it will be fundamentally important that these studies can be compared so that a common consensus can be reached and new therapeutic targets for obesity proposed.

Objective: We studied the effect of the biopsy sampling methods (needle-aspirated and surgical) used in clinical investigation programs on the functional interpretation of adipose tissue gene expression profiles.

Design: A comparative microarray analysis of the different subcutaneous adipose tissue sampling methods was performed in age-matched lean (n = 19) and obese (n = 18) female subjects. Appropriate statistical (principal components analysis) and bioinformatic (FunNet) functional enrichment software were used to evaluate data. The morphology of adipose tissue samples obtained by needle-aspiration and surgical methods was examined by immunohistochemistry.

Results: Biopsy techniques influence the gene expression underlying the biological themes currently discussed in obesity (eg, inflammation, extracellular matrix, and metabolism). Immunohistochemistry experiments showed that the easier to obtain needle-aspirated biopsies poorly aspirate the fibrotic fraction of subcutaneous adipose tissue, resulting in an underrepresentation of the stroma-vascular fraction.

Conclusions: The adipose tissue biopsy technique is an important caveat to consider when designing, interpreting, and, most important, comparing microarray experiments. These results will have crucial implications for the clinical and physiopathologic understanding of human obesity and therapeutic approaches.

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