Chickens Selected for High Body Weight Show Relative Impairment in Fatty Acid Oxidation Efficiency and Metabolic Flexibility in Skeletal Muscle and White Adipose Tissue

The ability to adapt fuel usage to nutrient availability is termed metabolic flexibility, and is influenced by activity of the pyruvate dehydrogenase complex (PDC). The Virginia lines of chickens are a unique model of anorexia and obesity that have resulted from 56 generations of artificial selection for high (HWS) or low (LWS) juvenile body weight. We hypothesized that hyperphagia and obesity in juvenile HWS chickens are associated with altered fatty acid oxidation efficiency and metabolic flexibility in tissues associated with energy sensing and storage, and relative cellular hypertrophy in white adipose tissue. Hypothalamus, liver, Pectoralis major, gastrocnemius, abdominal fat, clavicular fat and subcutaneous fat were collected from juvenile (56-65 day-old) HWS and LWS chickens for metabolic, gene expression and histological assays. The HWS chickens had reduced fatty acid oxidation efficiency in abdominal fat (P < 0.0001) and reduced rates of oxidation in abdominal fat and gastrocnemius (P < 0.0001) as compared to LWS. There was reduced citrate synthase activity in white adipose tissue (P < 0.0001) and greater metabolic inflexibility in skeletal muscle (P = 0.006) of HWS compared to LWS. Greater pyruvate dehydrogenase kinase 4 (PDK4) and forkhead box O1 (FoxO1) mRNA were found in skeletal muscle and white adipose tissue of 56-day-old HWS than LWS. Expression of peroxisome proliferator-activated receptor γ (PPARγ) in all adipose tissue depots was greater (P < 0.05) in LWS than in HWS chickens. The HWS chickens had larger (P < 0.0001) and fewer (P < 0.0001) adipocytes per unit area than LWS. These results suggest that the HWS chickens have impaired metabolic flexibility and fatty acid oxidation efficiency due to an up-regulation of pyruvate dehydrogenase activity to accommodate the influx of acetyl CoA from fatty acid oxidation in skeletal muscle and white adipose tissue. These metabolic adaptations can be linked to differences in gene expression regulation and body composition between the lines. Adipocyte cellularity data are consistent with greater oxidative efficiency in the adipose tissue of LWS, because of the greater number of unfilled cells in all depots that were sampled. Results can be extrapolated to agricultural production in the understanding of factors regulating the amount of lipid deposition in chicken carcass fat. Results may also provide insight into eating disorders and the development of obesity.