Fig. 4: Effects of lipid metabolic reprogramming on CRC.

1) In fatty acid metabolism, LDs and PGE2 are upregulated through ATGL/HSL-FAA, PGE2/EP4 and PGE2/EP1-Fas/FasL to upregulate M2 TAMs and downregulate CD8 + T cells. And upregulation of CPT1A, a key enzyme in fatty acid metabolism, also downregulates T cells and Teffs in two different ways. In sum, the end result of fatty acid metabolism contributes to the immune escape of CRC. 2) Upregulation of cholesterol itself activates the ROS- NLRP3-CCL5-p65/STAT3- CSN5-PD-L1 pathway to directly promote cancer cell growth, and in another way downregulates CD8 + T cells through the rise of PD-L1 and marker 2B4. This is followed by a rise in its product DCA, which in turn downregulates CD8 + T cells, p53 and converts regulatory T cells to proinflammatory one through upregulation of beta-linked proteins in three ways, all of which ultimately promote CRC development. 3) Phospholipids upregulate CD8 + T cells via agpat4/LPA/p38/p65-IL1β/IL-6 upregulation; on the other hand, phospholipids also upregulate M1 macrophage-dependent T-cells via camptothesomes. ultimately phospholipids act as heterodimers in metabolic reprogramming to inhibit CRC. LDs lipid drops; PGE2 prostaglandin E2; CPT1A carnitine palmitoyltransferase 1 A; ATGL adipose triglyceride lipase; HSL hormone-sensitive lipase; DCA deoxycholic acid; LPA lysophosphatidicacid.