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

Abstract

Background: Intermittent fasting, 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. Intermittent fasting is also widely practiced in the rearing of so-called broiler breeders, the parent stock of meat-type chickens, who require strict feed restriction regimens to prevent the serious health problems associated with their voracious appetites. Although intermittent fasting has been extensively used in this context to reduce feed competition and its resulting stress it has not usually been considered as a health-span promoter, but presents an alternative and complementary model to rodent studies. In both mammals and birds, the liver is one of the main responders to variations in energy balance. In this paper we examine the liver transcriptomics of wild-type Red Junglefowl chickens fed either ad libitum, chronically restricted to around 70% of ad libitum daily or intermittently fasted on a 2:1 (2 days fed, 1 day fasted) schedule without actual caloric restriction using a microarray. Results: We find large effects of feeding regimen on liver transcriptomics, with most of the affected genes relating to energy metabolism. Interestingly we also find large, chronic effects on the transcription of a battery of cell proliferation-promoting genes. Similar regenerative effects have been reported in rodents, where they have been associated with reduced levels of circulating leptin. A small number of inflammation-related genes also show chronically changed expression profiles. Conclusions: The increase in proliferative potential suggested by the gene expression changes reported here is a first indication that birds and mammals respond similarly to intermittent fasting practices. Our findings may indicate that the health benefits of periodic caloric restriction are ubiquitous and note restricted to mammals alone. The mechanisms underpinning these benefits are, however, unclear as leptin has been associated with these benefits in mammals but does not have endocrine function in birds. The observed effects on inflammation-related genes may be either beneficial or detrimental for the animal and could warrant further investigation.