To help explain these apparently conflicting observations, we will briefly consider nutrient mobilization during intense inflammation. Whereas glycogenolysis and gluconeogenesis are frequently reported during intense inflammation, significant mobilization and catabolism of glucose may have significantly increased liver glucose and its glucose metabolites, including acetyl Co-A, pyruvate and citrate, levels in both MOSand VIRG-fed hosts. In the absence of innate immune responses at 24 h post-LPS challenge, increased activity of CS, a key enzyme involved in TCA cycle, revealed that energy demands of MOS-fed hosts were mainly derived from liver glucose/glucose metabolites that accumulated earlier. BAY-60-7550 Evidently, intestinal gluconeogenesis and liver glycolysis were not necessary and repressed. In VIRG-fed hosts, however, elevated innate immune responses at 24 h post-LPS challenge required higher energy. Insufficient energy derived from accumulated liver glucose/glucose metabolites necessitated further glucose mobilization and catabolism through intestinal gluconeogenesis and liver glycolysis, respectively. However, as evidenced by ACLY up-regulation, INCB28060 exceptionally high liver citrate levels, which accumulated during intense inflammation, triggered CS down-regulation. Citrate is well recognized as a potent allosteric negative-feedback inhibitor of CS activity and plays a crucial role in liver metabolic activities. Evidently, to rapidly catabolize and deplete the accumulated liver cytosolic citrate after its efflux from the mitochondria where it is synthesized, ACLY upregulation generated high acetyl Co-A levels, ME up-regulation increased liver NADPH concentrations, whereas FAS upregulation synthesized palmitate, the major fatty acid that ultimately yields long fatty acid chains, from acetyl Co-A, NADPH and malonyl Co-A, which is synthesized from acetyl Co-A by acetyl Co- A carboxylase. ACLY, ME and FAS are key lipogenic enzymes that convert liver cytoplasmic citrate into fatty acids. The preferential acetyl Co-A and NADPH utilization in de novo fatty acid biosynthesis mediated by ACLY, ME and FAS upregulations is consistent with published reports. In previously fasted and refed rats and chickens, increased liver lipogenesis was also mediated by ACLY, ME and FAS up-regulations,. While increased glucose mobilization and decreased fatty acid synthesis have frequently been reported during intense inflammation,, here we report that the liver rapidly metabolized citrate into fatty acids to restore its citrate homoeostatic level during late inflammation in addition to glucose mobilization for body energy requirements. In agreement with O��Hea and Leveille, we observed that livers in chickens derived most of the NADPH required for fatty acid synthesis from the ME reaction, whereas livers in rats obtained about 65% of NADPH from the pentose phosphate pathway.