Submitted to: Comparative Biochemistry and Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/5/2009
Publication Date: 5/8/2009
Citation: Proszkowiec-Weglarz, M., Richards, M.P., Humphrey, B., Rosebrough, R.W., McMurtry, J.P. 2009. AMP-activated protein kinase and carbohydrate response element binding protein: A study of two potential regulatory factors in the hepatic lipogenic program of broiler chickens. Journal of Comparative Biochemistry and Physiology. 154(1):68-79. Interpretive Summary: A primary goal of poultry producers today is to improve the efficiency and profitability of meat production. To meet this goal, poultry breeders have placed major emphasis on selecting lines of broiler chickens that grow faster and produce more meat than previous generations. However, along with improvements in these economically important traits have come some unintended changes in voluntary feed intake and body composition. Commercial lines of broiler breeder chickens tend to overeat when given free access to feed. This can result in an energy imbalance characteristic of obesity that leads to excessive accumulation of abdominal fat and a variety of health-related problems if access to feed is not strictly regulated. In fact, abdominal fat is now regarded as a major source of waste by poultry processors and an important cause of reduced profits for producers. In order to address this problem, it is important to first understand the underlying genetic basis for energy balance and fattening in poultry. In this study, we investigated key genes involved in controlling fatty acid synthesis in the liver of broiler chickens. A major objective of this work was to study how the function of these genes is regulated by nutrients and hormones and the specific molecular mechanisms involved. Our findings offer new insights into the potential impact of current poultry breeding and management practices on fat accumulation in broiler chickens. This information is useful to researchers studying the control of lipid metabolism in avian species, as well as, to poultry producers in formulating new genetic selection and feeding strategies for use in commercial poultry flocks.
Technical Abstract: This study investigated the effects of fasting and refeeding on AMP-activated protein kinase (AMPK) and carbohydrate response element binding protein (ChREBP) mRNA, protein and activity levels; as well as the expression of lipogenic genes involved in regulating lipid synthesis in broiler chicken liver. Fasting for 24 or 48 h produced significant declines in plasma glucose (at 24 h), insulin and thyroid hormone (T3) levels that were accompanied by changes in mRNA expression levels of hepatic lipogenic genes. The mRNA levels of acetyl-CoA carboxylase (ACC), ATP-citrate lyase (ACL), fatty acid synthase (FAS), thyroid hormone responsive Spot 14 (Spot 14), malic enzyme (ME) and stearoyl-CoA desaturase-1 (SCD-1) declined in response to fasting. Refeeding for 24 h increased mRNA levels for each of these genes, characterized by a significant increase (‘overshoot’) above fed control values. No change in mRNA expression of the two AMPK a subunit genes was observed in response to fasting or refeeding. In contrast, ChREBP and sterol regulatory element binding protein-1 (SREBP-1) mRNA levels decreased during fasting and increased with refeeding. Phosphorylation of AMPK a subunits increased modestly after a 48 h fast. However, there was no corresponding change in the phosphorylation of ACC, a major downstream target of AMPK. Surprisingly, protein level and DNA-binding activity of ChREBP increased during fasting and declined upon refeeding as measured in whole liver tissue extracts. In general, evidence was found for coordinate transcriptional regulation of lipogenic program genes in broiler chicken liver, but specific regulatory roles for AMPK and ChREBP in that process remain to be further characterized.