Microarray profiling of human white adipose tissue after exogenous leptin injection

• Published in: European journal of clinical investigation 2006-03, Vol.36 (3), p.153-163
• Main Authors: Taleb, S., Van Haaften, R., Henegar, C., Hukshorn, C., Cancello, R., Pelloux, V., Hanczar, B., Viguerie, N., Langin, D., Evelo, C., Zucker, J., Clément, K., Saris, W. H. M.
• Format: Article
• Language: English
• Subjects: Adipocytes - immunology; Adipose tissue; Adipose Tissue - drug effects; Adipose Tissue - immunology; Adult; Biological and medical sciences; Body fat; Cytokines - genetics; DNA, Circular - analysis; Gene Expression Regulation - genetics; General aspects; Humans; Inflammation - genetics; Inflammation - immunology; inflammation and gene profiling; Injections; Leptin - administration & dosage; Leptin - analogs & derivatives; Leptin - blood; Leptin - genetics; Male; Medical sciences; Oligonucleotide Array Sequence Analysis - methods; PEG-OB; Polyethylene Glycols - administration & dosage; Recombinant Proteins - administration & dosage; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Messenger - analysis
• ISSN: 0014-2972; 1365-2362
• DOI: 10.1111/j.1365-2362.2006.01614.x

Background  Leptin is a secreted adipocyte hormone that plays a key role in the regulation of body weight homeostasis. The leptin effect on human white adipose tissue (WAT) is still debated. Objective  The aim of this study was to assess whether the administration of polyethylene glycol‐leptin (PEG‐OB) in a single supraphysiological dose has transcriptional effects on genes of WAT and to identify its target genes and functional pathways in WAT. Materials and methods  Blood samples and WAT biopsies were obtained from 10 healthy nonobese men before treatment and 72 h after the PEG‐OB injection, leading to an approximate 809‐fold increase in circulating leptin. The WAT gene expression profile before and after the PEG‐OB injection was compared using pangenomic microarrays. Functional gene annotations based on the gene ontology of the PEG‐OB regulated genes were performed using both an ‘in house’ automated procedure and GenMAPP (Gene Microarray Pathway Profiler), designed for viewing and analyzing gene expression data in the context of biological pathways. Results  Statistical analysis of microarray data revealed that PEG‐OB had a major down‐regulated effect on WAT gene expression, as we obtained 1822 and 100 down‐ and up‐regulated genes, respectively. Microarray data were validated using reverse transcription quantitative PCR. Functional gene annotations of PEG‐OB regulated genes revealed that the functional class related to immunity and inflammation was among the most mobilized PEG‐OB pathway in WAT. These genes are mainly expressed in the cell of the stroma vascular fraction in comparison with adipocytes. Conclusion  Our observations support the hypothesis that leptin could act on WAT, particularly on genes related to inflammation and immunity, which may suggest a novel leptin target pathway in human WAT.