CELL ENERGY: Cells mostly use glucose as the source of energy; however, few cells use fatty acids or amino acids as the source of energy depending on their energetic demands [5-7]. Typically, the cell allows the uptake of these energy-rich molecules through glycolysis and enter the TCA cycle, and the electron transport chain (ETC) to produce ATP [8, 9]. Glycolysis involves the uptake of extracellular glucose into cells through the glucose transporter 1 (GLUT1) and subsequent conversion into pyruvate along with numerous other products inside the cytosol [10]. This glucose metabolism is a relatively inefficient pathway in terms of cellular ATP production; however, it provides a way to maintain redox balance inside the cell (to reduce NAD+ into NADH), which is subsequently used by various enzymes as a cofactor and enables the diversion of metabolic intermediates to biosynthetic growth pathways to support anabolic growth [11, 12]. The TCA cycle occurs in the mitochondrial matrix and it uses pyruvate as a substrate [13], which is converted into acetyl coenzyme A (CoA) to generate energy-rich electron carriers NADH and FADH2. These electron carriers transport electrons through oxidative phosphorylation (OXPHOS) to the inner mitochondrial membrane into the ETC to generate a hydrogen gradient required for the synthesis of ATP [14]. Besides, the fatty acid oxidation (FAO) pathway, which is a key catabolic pathway for energy production, involves the mitochondrial conversion of fatty acids into several products that are subsequently used by the cell to generate energy using fatty acids instead of glucose [7]. Activation of the fatty acid is the first step of FAO to occur in the cytosol that generates acetyl-CoA, which then enters the TCA to generate electron carriers, and then enter the ETC to generate energy [15]. In the context of immunity, a high rate of glucose metabolism has been found in lipopolysaccharide (LPS)-activated macrophages and dendritic cells (DCs), activated natural killer (NK) cells, activated effector T cells, and activated B cells [16-20]. Indeed, this upregulation of glycolysis in immune cells can be considered a hallmark metabolic change for immune cells that are undergoing rapid activation, explicitly in response to stimulation of pattern recognition receptor (PRR), cytokine receptors, or antigen receptors. Aerobic glycolysis has been associated with inflammatory and rapidly proliferating immune cells; however, dependency on FAO has been observed in many non-inflammatory immune cells and show raised cellular lifespans, including M2 macrophages, Tregs, and memory T cells [7, 21-23]. In contrast to FAO, fatty acid synthesis regulates the generation and activation of pro-inflammatory immune cells. Therefore, inflammatory signal leads to fatty acid synthesis of inflammatory immune cells, whereas tolerogenic stimuli drive FAO of non-immune cells. Moreover, activated T cells also use few amino acids, especially glutamine metabolites to generate α-ketoglutarate as a substrate of the TCA cycle to generate energy, and most importantly, through the mTOR pathway for sensing amino acid levels inside the cell and for nucleotide synthesis [24-26].