Both fasted and insulin neutralized birds exhibited sig nificant increases in plasma glucagon. Parallel elevations in plasma NEFA Ivacaftor VX-770 suggested that this resulted in significant lip olysis of stored triacylglycerol in both treatment groups. During fasting, a considerable percentage of the liberated fatty acids are re esterified in adipocytes, and only a small fraction traditionally have been thought to be oxidized in the mitochondria of adipocytes through beta oxidation. However, recent studies in mice and in human adi pose tissue demonstrate that in some conditions fatty acid oxidation in white adipose tissue is considerable and may be an important determinant of obesity.

Consistent with this concept, we found significant increases in a num ber of key enzymes that mediate mobilization of fatty acids and their oxidation, including the rate limiting enzymes in both mitochondrial and peroxisomal fatty acid oxidation. We measured tissue levels of beta hydroxybutyrate, a ketone product of beta oxidation, to confirm that changes in gene expression had functional consequences and found them to be signifi cantly elevated in adipose tissue of fasted vs. fed chickens. Levels were numerically but not statistically higher in insulin neutralized adipose tissue. Qualitatively, fasting induced changes in gene expression resemble those induced by the fibrate class of drugs, which activate PPAR and promote fatty acid oxidation in white adipose tissue and are used clinically to treat hyper lipidemia.

These data suggest that dietary acti vation of PPAR, for example through supplementation with fatty acids that preferentially bind and activate this member of the PPAR family, may be a means to at tenuate fat deposition in commercial broilers. Such action may underlie the reduced abdominal fat mass reported in broilers that were fed diets rich in n 3 PUFA. Both fasting and insulin neutralization elicited marked upregulation of PDK4. PDK4 is a nutrient sensing fuel switch that phosphorylates and inactivates pyruvate de hydrogenase, which shifts fuel use from glucose to fatty acids and spares glucose for the brain during periods of fasting. PDK4 also enhances glycerol synthesis in white adipose tissue by shunting pyruvate into glycero neogenesis, at least in the fed state. Hepatic and skel etal muscle expression of PDK4 is increased by fatty acids, acetyl CoA, NADH and the diabetic state and decreased by insulin and pyruvate.

Little is known about PDK4 in chicken, but a recent study suggests it acts as a glycogen sensor in muscle and thus plays comparable roles to those in mammals. In mouse white adipose tissue, PDK4 expression was shown to be induced Drug_discovery by acti vation of p38MAPK, which we found to be signifi cantly up regulated with fasting and, to a lesser extent, with insulin neutralization.