Abstract
BackgroundThe co-morbidities of obesity are tied to location of excess fat in the intra-abdominal as compared to subcutaneous white adipose tissue (WAT) depot. Genes distinctly expressed in WAT depots may impart depot-dependent physiological functions. To identify such genes, we prepared subtractive cDNA libraries from murine subcutaneous (SC) or intra-abdominal epididymal (EP) white adipocytes.ResultsDifferential screening and qPCR validation identified 7 transcripts with 2.5-fold or greater enrichment in EP vs. SC adipocytes. Boc, a component of the hedgehog signaling pathway demonstrated highest enrichment (~12-fold) in EP adipocytes. We also identified a dramatic enrichment in SC adipocytes vs. EP adipocytes and in SC WAT vs. EP WAT for transcript(s) for the major urinary proteins (Mups), small secreted proteins with pheromone functions that are members of the lipocalin family. Expression of Boc and Mup transcript was further assessed in murine tissues, adipogenesis models, and obesity. qPCR analysis reveals that EP WAT is a major site of expression of Boc transcript. Furthermore, Boc transcript expression decreased in obese EP WAT with a concomitant upregulation of Boc transcript in the obese SC WAT depot. Assessment of the Boc binding partner Cdon in adipose tissue and cell fractions thereof, revealed transcript expression similar to Boc; suggestive of a role for the Boc-Cdon axis in WAT depot function. Mup transcripts were predominantly expressed in liver and in the SC and RP WAT depots and increased several thousand-fold during differentiation of primary murine preadipocytes to adipocytes. Mup transcripts were also markedly reduced in SC WAT and liver of ob/ob genetically obese mice compared to wild type.ConclusionFurther assessment of WAT depot-enriched transcripts may uncover distinctions in WAT depot gene expression that illuminate the physiological impact of regional adiposity.
Highlights
The co-morbidities of obesity are tied to location of excess fat in the intraabdominal as compared to subcutaneous white adipose tissue (WAT) depot
Genes that were identified in our suppressive subtractive hybridization (SSH) screening showing differential transcript expression in EP adipocytes vs. SC adipocytes were validated by quantitative polymerase chain reaction (qPCR)
brother of Cdon (Boc) transcript level similar to that for SC is noted in RP WAT and brown adipose tissue (BAT)
Summary
The co-morbidities of obesity are tied to location of excess fat in the intraabdominal as compared to subcutaneous white adipose tissue (WAT) depot. Various studies in humans and rodents have illuminated distinctions in the physiology, lipolytic response, gene expression and other aspects of adipocytes present in different WAT depots [5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20]. BMC Genomics 2008, 9:397 http://www.biomedcentral.com/1471-2164/9/397 pose depots are best regarded as separate "miniorgans" [10] These distinctions, and their molecular underpinnings, are gaining in importance with the realization that it is the anatomical location of excess adipose tissue that appears to underlie the health impact of obesity, and that interventions targeting reduction of intra-abdominal fat mass can effectively combat obesity-related diseases [15,21,22,23,24,25]. A complete and defining picture of WAT depot dependent gene expression, as well as the underlying regulatory events governing depot-dependent gene expression, is yet to be identified
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