Gene expression profiling of the short-term adaptive response to acute caloric restriction in liver and adipose tissues of pigs differing in feed efficiency

Authors: LKHAGVADORJ, SENDER - Iowa State University; QU, LONG - Iowa State University; CAI, WEIGUO - Iowa State University; COUTURE, LOIVER - Iowa State University; Barb, Claude; Hausman, Gary; NETTETON, DAN - Iowa State University; ANDERSON, LLOYD - Iowa State University; DECKERS, JACK - Iowa State University; TUGGLE, CHRIS - Iowa State University

Submitted to: American Journal of Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/25/2009
Publication Date: 2/1/2010
Citation: Lkhagvadorj, S., Qu, L., Cai, W., Couture, L., Barb, C.R., Hausman, G.J., Netteton, D., Anderson, L., Deckers, J., Tuggle, C. 2010. Gene expression profiling of the short-term adaptive response to acute caloric restriction in liver and adipose tissues of pigs differing in feed efficiency. American Journal of Physiology. 298:R494-R507.

Interpretive Summary: Efficient use of this feed by the pigs to produce live weight is important to swine producers. Selection for feed efficiency has been relatively unsuccessful at changing feed efficiency. Selection for lean growth rate has been shown to improve feed efficiency and has been used by many pig breeding companies. As pigs are approaching optimum levels of lean, new methods for improving feed efficiency are needed. The trait residual feed intake could be a trait that could be used to improve feed efficiency. This study will provide understanding of the underlying genetic and physiological basis of feed intake and efficiency, and suggest specific genes to target for genetic improvement through marker-assisted selection. Pigs selected for low and high residual feed intake (RFI) were subjected to 8 day feed restriction to identify genes and pathways that respond to feed restriction with different RFI in liver and adipose tissue. In the RFI pig the same genes that respond to RFI also resond to feed restriction. Genes involved in energetically costly lipid biosynthesis were down-regulated and shifted to energy conservation and efficient utilization pathways in RFI pigs. These results will provide an understanding of the underlying genetic and physiological basis of feed efficiency and will provide specific genes to target for genetic improvement through marker-assisted selection.

Technical Abstract: Residual feed intake (RFI) is a measure of feed efficiency, where low RFI denotes high feed efficiency. Caloric restriction (CR) is associated with feed efficiency in livestock species and relevant to human health benefits such as longevity and cancer prevention. We generated transcript profiles of liver and subcutaneous adipose tissue with serum metabolite analyses and identified genes and pathways that are differentially expressed in response to CR or between pigs with different RFI values. Prepubertal Yorkshire gilts with low RFI (n=10) or high RFI (n=10) were fed ad libitum or 80% of maintenance diet for 8 days in a 2'2 factorial design. 6,114 genes in fat and 305 genes in liver were differentially expressed (DE) in response to CR and 311 fat genes and 147 liver were DE due to RFI group. Pathway analyses of CR-induced DE genes indicated a switch to a conservation mode of energy by down-regulating lipid and steroid synthesis in both liver and fat. Also, CR altered expression of fat genes in immune response and cell cycle/apoptotosis pathways, which may explain some of the CR-driven lifespan enhancement reported in other species. In-silico analysis of transcription factors revealed ESR1 as a putative regulator of adaptive response to CR and several targets of ESR1 in our DE genes lists were annotated as cell cycle/apoptosis genes. A common between overrepresented annotation in genes down-regulated by both CR and RFI differences was the lipid metabolic pathway. We propose a common energy conservation mechanism, which may be controlled by PPARA, PPARG, and/or CREB1 in both CR and feed efficient pigs.