Intermittent fasting induces chronic changes in the hepatic gene expression of Red Jungle Fowl (Gallus gallus)

Abstract

Abstract Background Intermittent fasting (IF), the implementation of fasting periods of at least 12 consecutive hours on a daily to weekly basis, has received a lot of attention in recent years for imparting the life-prolonging and health-promoting effects of caloric restriction with no or only moderate actual restriction of caloric intake. IF is also widely practiced in the rearing of broiler breeders, the parent stock of meat-type chickens, who require strict feed restriction regimens to prevent the serious health problems associated with their intense appetites. Although intermittent fasting has been extensively used in this context to reduce feed competition and its resulting stress, the potential of IF in chickens as an alternative and complementary model to rodents has received less investigation. In both mammals and birds, the liver is a key component of the metabolic response to IF, responding to variations in energy balance. Here we use a microarray analysis to examine the liver transcriptomics of wild-type Red Jungle Fowl chickens fed either ad libitum, chronically restricted to around 70% of ad libitum daily or intermittently fasted (IF) on a 2:1 (2 days fed, 1 day fasted) schedule without actual caloric restriction. As red junglefowl are ancestral to domestic chicken breeds, these data serve as a baseline to which existing and future transcriptomic results from farmed birds such as broiler breeders can be compared. Results We find large effects of feeding regimen on liver transcriptomics, with most of the affected genes relating to energy metabolism. A cluster analysis shows that IF is associated with large and reciprocal changes in genes related to lipid and carbohydrate metabolism, but also chronic changes in genes related to amino acid metabolism (generally down-regulated) and cell cycle progression (generally up-regulated). The overall transcription pattern appears to be one of promoting high proliferative plasticity in response to fluctuations in available energy substrates. A small number of inflammation-related genes also show chronically changed expression profiles, as does one circadian rhythm gene. Conclusions The increase in proliferative potential suggested by the gene expression changes reported here indicates that birds and mammals respond similarly to intermittent fasting practices. Our findings therefore suggest that the health benefits of periodic caloric restriction are ubiquitous and not restricted to mammals alone. Whether a common fundamental mechanism, for example involving leptin, underpins these benefits remains to be elucidated.