PATHWAY PROFILING IDENTIFIES MECHANISMS OF ADIPOSE DEPOSITION IN DOMESTIC CHICKENS

The domestic chicken is an attractive, but underutilized, animal model for studies of adipose tissue biology, metabolism and obesity: 1.) like humans, chickens rely on liver rather than adipose tissue for the majority of de novo lipogenesis; 2.) quantitative trait loci (QTLs) linked to fatness in chickens contain genes implicated in human susceptibility to obesity and diabetes; 3.) chickens are naturally hyperglycemic and insulin resistant; and 4.) a broad selection of genetic models exhibiting a range of fatness are available. To date, however, little is known about regulation of adipose metabolism in this model organism.

Affymetrix arrays were used to profile gene expression in abdominal adipose tissue from broiler chickens fed ad libitum or fasted for five hours. Quantitative real time polymerase chain reaction (QPCR) was used to validate microarray results for select genes. A total of 1780 genes were differentially expressed in fasted vs. ad libitum fed (p<0.05) tissue after correction for multiple testing. Gene Ontology and pathway analyses, combined with Western blot validation, indicated significant effects on a broad selection of pathways related to metabolism, stress signaling and adipogenesis. In particular, fasting upregulated rate-limiting genes in both the mitochondrial and peroxisomal pathways of beta-oxidation. Enhanced fatty acid oxidation in white adipose tissue was further suggested by a significant increase in tissue content of the ketone betahydroxybutyrate. Expression profiles suggested that, despite the relatively brief duration of feed withdrawal, fasting suppressed adipogenesis; expression of key genes in multiple steps of adipogenesis, including lineage commitment from mesenchymal stem cells, were significantly down-regulated in fasted vs. fed adipose tissue. Interestingly, fasting increased expression of several inflammatory adipokines and components of the toll-like receptor 4 signaling pathway. A second study with Affymetrix microarrays of Fayoumi, Leghorn and broiler adipose tissue revealed that genetic leanness shared molecular signatures with the effects of fasting. In supervised clustering analysis, fasted broiler chickens clustered with lean Fayoumi and Leghorn lines rather than with the fed broiler group, suggesting that fasting manipulated expression profiles to resemble those of the lean phenotype.