Regulation of lipid storage and inflammation in the liver by CEACAM1

This review focuses on a special aspect of hepatic lipid storage and inflammation that occurs during nutritional excess in obesity. Mounting evidence supports that prolonged excess fatty acid (FA) uptake in the liver is strongly associated with hepatic lipid storage and inflammation and that the two processes are closely linked by a homeostatic mechanism. There is also strong evidence that bacterial lipids may enter the gut by a common mechanism with lipid absorption and that there is a set point to determine when their uptake triggers an inflammatory response in the liver. In fact, the progression from high uptake of FAs in the liver resulting in Metabolic dysfunction‐associated steatotic liver disease (MASLD) to the development of the more serious Metabolic dysfunction‐associated steatohepatitis (MASH) depends on the degree of inflammation and its progression from an acute to a chronic state. Thus, MASLD/MASH implicates both excess fatty acids and progressive inflammation in the aetiology of liver disease. We start the discussion by introduction of CD36, a major player in FA and lipopolysaccharide (LPS) uptake in the duodenum, liver and adipose tissue. We will then introduce CEACAM1, a major player in the regulation of hepatic de novo lipogenesis and the inflammatory response in the liver, and its dual association with CD36 in enterocytes and hepatocytes. We conclude that CEACAM1 and CD36 together regulate lipid droplet formation and inflammation in the liver. CEACAM1 associates with fatty acid (FA) binding protein CD36 in hepatocytes, and in the presence of LPS, forms a complex with TLR4 that phosphorylates SYK generating an inflammatory response. At the same time, phosphorylation of the ITIMs on CEACAM1 by SRC leads to recruitment of tyrosine phosphatase SHP2 that dampens the inflammation by dephosphorylation of SYK. During excess FAs and inflammation, hepatocytes begin to store triglyceride (TG) as lipid droplets (LDs) rather that export TGs in VLDL and LDL.