Martin et al. BMC Genomics 2010, 11:418 http://www.biomedcentral.com/1471-2164/11/418 cytokine signalling 1 (SOCS1) [62], was decreased in the ASL group. SOCS1 functions to attenuate the inflamma- tory response to cytokines, hence the decrease in ASL may be a further indication that these fish do not nega- tively regulate their inflammatory response to the same degree as in fed fish. The effects of malnutrition on the APR in rats showed that animals on low protein diets had higher levels of APR transcripts in the liver [63] which was interpreted as a low level inflammatory response and hence a pre- servation of the APR during malnutrition. However other studies suggest an attenuated APR and cytokine response in humans which can lead to increased mor- bidity following infection [64]. Protein malnourishment in mammals can activate NFkB, leading to inflammation, however our results in fish do not find this to be the case, and in fact the transcription factors controlling these pathways were down regulated, with little evidence for increased transcription of inflammatory response genes in the starved fish. Despite the depletion of protein reserves the starved fish were still able to mount an APR, or at least induce expression of the genes. Our results suggest the ASL potentially had a greater magnitude of APR than the AFL group, but the APR alone is no indicator of the outcome of an infection. The removal of free radicals and toxins are achieved in part by antioxidants and we observed a number of antioxidant encoding genes being both increased and decreased during infection. In mammals that were on a restricted calorie intake a number of different isoforms of glutathione peroxidase were both increased and decreased [20]. In fish we have observed similar results with super oxide dismutase and glutathione peroxidase 3 increased in starved fish whereas glutathione peroxi- dase 2 was decreased following starvation. This may indicate these genes are controlled differently with glu- tathione peroxidase 3 perhaps having a greater role in detoxifying products of amino acid catabolism. Follow- ing infection glutathione peroxidase 2 was increased in both ASL and AFL groups which would indicate a requirement to remove reactive products of increased protein turnover and oxidation [65]. Several different glutathione-s-transferases were found reduced in expres- sion in the ASL fish. Interestingly glutathione-s-transfer- ase activity was down regulated in rainbow trout following 6 weeks starvation [66], a considerably longer time of starvation than in the present study indicating the decrease in the activity of this enzyme may be accel- erated by infection. The complement system which has major roles in innate and acquired immune defences has components differentially expressed following infection in both the ASL and AFL groups of fish. Activation of the Page 14 of 20 complement system during innate immune responses is via the “alternative pathway” or “lectin pathway” [67], with pathogen recognition resulting in increased tran- scription of complement components. Once activated the complement factors help neutralise pathogens by lysis and phagocytosis, and also act as inducers of inflammation [68]. Complement factors C3-1, C7, B, H and C1q were all increased which is an expected response to acute bacterial infection. However a number of complement factors were found to be down regulated after infection in the ASL group. Components C4 and C1q were both decreased in expression in the ASL group, and both are major factors of the classical com- plement pathway [69] involved in the binding of immu- noglobulin molecules to pathogens during an adaptive immune response. As the major response in this study is an innate response it is possible that this part of the pathway is being attenuated, particularly in the ASL group that has less energy reserves. However C6 was found down regulated in AFL, which is surprising as it is directly involved in the pathogen membrane attack complex and several complement B genes were found increased and decreased following infection. The differ- ential expression of complement factors can be antici- pated, as shown in trout infected with Listonella anguillarum where C7 was increased but C3 compo- nents down regulated [70] suggesting the control of the complement cascade is complicated with different com- ponents being independently regulated. Cholesterol and fatty acid metabolism was altered as a result of both starvation and infection. In starvation, several key rate limiting genes involved in the choles- terol biosynthesis pathway were significantly up regu- lated (Fig. 3). This would indicate a major increase in cholesterol biosynthesis, suggesting the fish are attempt- ing to maintain circulating levels of cholesterol. In fasted cod cholesterol in high density lipoprotein (HDL) increased in serum whereas there was a decrease in low density lipoprotein (LDL) [71]. Interestingly in the cholesterol pathway isopentyl pyrophosphase delta iso- merase was increased in the AFL group, as was a steroi- dogenic acute regulatory factor. However, one of the final enzymes in the production of cholesterol, 7 dehy- drocholesterol reductase was down regulated in the ASL fish indicating major differences in cholesterol metabo- lism between ASL and AFL groups, which was further supported by the reduction of a number of apolipopro- teins (Fig. 3) in ASL, that are responsible for lipid and cholesterol transport. The peroxisome proliferator acti- vated receptors (PPARs) are nuclear hormone receptors that act as transcription factors and are critical regula- tors of lipid and energy homeostasis [72], several of which have recently been described in fish [73]. In our experiments PPARa was increased following infection in