Differential gene expression pattern in hypothalamus of chickens during fasting-induced metabolic reprogramming: Functions of glucose and lipid metabolism in the feed intake of chickens

Fasting-induced hypothalamic metabolic reprogramming is involved in regulating energy homeostasis and appetite in mammals, but this phenomenon remains unclear in poultry. In this study, the expression patterns of a panel of genes related to neuropeptides, glucose, and lipid metabolism enzymes in the hypothalamus of chickens during fasting and refeeding were characterized by microarray analysis and quantitative PCR. Results showed that 48 h of fasting upregulated (P < 0.05) the mRNA expressions of orexigenic neuropeptide Y and agouti-related protein but downregulated (P < 0.05) that of anorexigenic neuropeptide pro-opiomelanocortin; growth hormone-releasing hormone; islet amyloid polypeptide; thyroid-stimulating hormone, beta; and glycoprotein hormones, alpha polypeptide. After 48 h of fasting, the mRNA expression of fatty acid beta-oxidation [peroxisome proliferator-activated receptor alpha (PPAR alpha), carnitine palmitoyltransferase 1A, and forkhead box O1], energy sensor protein [sirtuin 1 (SIRT1) and forkhead box O1], and glycolysis inhibitor (pyruvate dehydrogenase kinase, isozyme 4) were enhanced, but that of fatty acid synthesis and transport associated genes (acetyl-CoA carboxylase alpha, fatty acid synthase, apolipoprotein A-I, endothelial lipase, and fatty acid binding protein 7) were suppressed. Liver and muscle also demonstrated similar expression patterns of genes related to glucose and lipid metabolism with hypothalamus, except for that of acetyl-CoA carboxylase alpha, acyl-CoA synthetase long-chain family member 4, and apolipoprotein A-I. The results of intracerebro-ventricular (ICV) injection experiments confirmed that alpha-lipoic acid (ALA, pyruvate dehydrogenase kinase, isozyme 4 inhibitor, 0.10 mu mol) and NADH (SIRT1 inhibitor, 0.80 mu mol) significantly suppressed the appetite of chickens, whereas 2-deoxy-D-glucose (glycolytic inhibitor, 0.12 to 1.20 mu mol) and NAD(+) (SIRT1 activator, 0.08 to 0.80 mu mol) increased feed intake in chickens. The orexigenic effect of NAD(+) was also blocked by cotreatment with NADH. However, ICV injection of either GW7647 (PPAR alpha agonist) or GW6471 (PPAR alpha antagonist) showed no effects on feed intake. Results suggested that hypothalamic glycolysis (inhibited by ALA and promoted by 2-deoxy-D-glucose) and SIRT1 (inhibited by NADH and promoted by NAD(+)), not PPAR alpha, were probably involved in feed intake regulation in chickens.