Mfge8 regulates enterocyte lipid storage by promoting enterocyte triglyceride hydrolase activity.

ABSTRACT: The small intestine has an underappreciated role as a lipid storage organ. Under conditions of high dietary fat intake, enterocytes can minimize the extent of postprandial lipemia by storing newly absorbed dietary fat in cytoplasmic lipid droplets. Lipid droplets can be subsequently mobilized for the production of chylomicrons. The mechanisms that regulate this process are poorly understood. We report here that the milk protein Mfge8 regulates hydrolysis of cytoplasmic lipid droplets in enterocytes after interacting with the ?v?3 and ?v?5 integrins. Mice deficient in Mfge8 or the ?v?3 and ?v?5 integrins accumulate excess cytoplasmic lipid droplets after a fat challenge. Mechanistically, interruption of the Mfge8-integrin axis leads to impaired enterocyte intracellular triglyceride hydrolase activity in vitro and in vivo. Furthermore, Mfge8 increases triglyceride hydrolase activity through a PI3 kinase/mTORC2-dependent signaling pathway. These data identify a key role for Mfge8 and the ?v?3 and ?v?5 integrins in regulating enterocyte lipid processing.

SUBMITTER: Khalifeh-Soltani A 

PROVIDER: S-EPMC5085605 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature