Identifying metabolic pathways associated with leanness using domestic chickens as a model

Abstract

Domestic broiler chickens rapidly accumulate adipose tissue and are naturally hyperglycemic and insulin resistant, making them an attractive model for the study of obesity and insulin resistance. We previously showed that 5‐hour fasting rapidly upregulated pathways that would limit fat storage and promote fatty acid oxidation in broiler white adipose tissue. Our current objective was to determine if genetically determined leanness in chickens was due to activation of the same pathways induced by fasting. We used Affymetrix microarrays to identify differentially expressed genes in white adipose tissue of Fayoumi and broilers, which differ in adiposity by approximately 3‐fold. Cluster analysis revealed distinct similarities between expression profiles of lean Fayoumi and fasted broilers, compared to fed broilers, including genes involved in substrate oxidation. Lean chickens showed significant upregulation of energy‐sensing signaling pathways in white adipose tissue based on mRNA and Western blot analyses, including upregulation of the 5’ AMP‐activated protein kinase (AMPK) pathway. Adipose metabolites and fatty acid profiles were measured using LC‐MS/MS and GC‐MS, respectively. Our results indicated significant differences in adipose metabolism, stress signaling and adipogenesis between genetically lean and fatty lines of chickens, which may have relevance for studies of human obesity.