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Microarray profiling of human white adipose tissue after exogenous leptin injection
Author(s) -
Taleb S.,
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.
Publication year - 2006
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.2006.01614.x
Subject(s) - leptin , white adipose tissue , microarray analysis techniques , microarray , biology , adipose tissue , gene expression profiling , gene expression , gene , endocrinology , dna microarray , medicine , genetics , obesity
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.