Suggesting that proper turnover of these cells is also important for homeostasis of intestinal immunity. In the present study, we found that IECspecific ablation of Shp2 resulted in impaired migration of IECs along the crypt-villus axis. A delayed turnover of IECs may thus also contribute to intestinal inflammation in Shp2 CKO mice. In summary, we have shown that Shp2 is necessary for homeostasis of IECs, in particular for that of absorptive enterocytes and goblet cells, as well as for protection against colitis. These functions of Shp2 are likely mediated by activation of Ras. Further investigation will be required, however, to clarify the molecular mechanism by which Shp2 in IECs regulates intestinal immunity and protects against colitis. The use of fat-rich feeds has made fish farming more cost effective because protein is a relatively expensive source of energy. Supplementing diets with fat enables protein to be ”spared” for the synthesis of new tissue. Indeed, increasing dietary lipid levels supports higher growth rates and spares dietary protein in some species. However, too much dietary lipid often leads to unwanted fat deposition in the liver, inducing a condition referred to as ”fatty liver”. Fatty liver is often considered in a negative light in cultured fish because it represents wasted energy; indeed, there is little point in supplying an energy-yielding nutrient that is simply deposited unused in tissues stores. Furthermore, the health of fish may be affected by fatty liver, which often closely positively correlates with mortality. Therefore, it is necessary to AG-013736 319460-85-0 investigate the nutritional factors and mechanisms that affect the development of fatty liver. It has generally been assumed that, in mammals, attenuated hepatic fatty acid b-oxidation is a common feature of fatty liver. According to Du et al., impaired hepatic boxidation capacity also occurs when fish are fed fat-rich diets. To the best of our knowledge, few R428 Axl inhibitor studies have looked at b-oxidation regulation. Carnitine palmitoyltransferase I is considered to be the key regulatory enzyme in mitochondrial b-oxidation because it catalyzes the conversion of fatty acyl-CoAs into fatty acyl-carnitine molecules for entry into the mitochondrial matrix. The regulation of CPT I is complex, including allosteric inhibition by malonyl-CoA, changes in the expression of the CPT I gene and transcription factors, and changes in the mitochondrial membrane composition. Estimating kinetic constants is critical to describe enzyme-catalyzed reactions. However, it is not known how these regulatory mechanisms affect the activity and kinetics of CPT I in fish fed a high-fat diet. Evaluation of the major sites of lipid catabolism may provide further insight into the cause of excessive liver fat deposition in cultured fish. Blunt snout bream is an herbivorous freshwater fish native to China. Due to its fast growth, tender flesh, and high disease resistance, this species has been widely favored for aquaculture in China. However, comparable to a number of other commercially produced fishes, its artificial rearing is often associated with the occurrence of fatty liver, which correlates closely with a high rate of mortality or poor growth. Considering this, the present study evaluated hepatic FA boxidation and its regulation in blunt snout bream fed low- or highfat diets.