Mfge8 regulates enterocyte lipid storage by promoting enterocyte triglyceride hydrolase activity

Khalifeh-Soltani, Amin; Dk, Gupta; Ha, Arnold; Iqbal, Jahangir; Hussain, M. Mahmood; Podolsky, Michael J.; Atabai, Kamran

doi:10.1172/jci.insight.87418

Cited by 34 publications

(50 citation statements)

References 57 publications

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“…CD103 is integrin alpha E. This integrin has not been implicated in formation of LB. However, other intergins (primarily αvβ3 and αvβ5) were shown to be important for this process 49 , 50 .…”

Section: Discussionmentioning

confidence: 98%

Lipid bodies containing oxidatively truncated lipids block antigen cross-presentation by dendritic cells in cancer

et al. 2017

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Cross-presentation is a critical function of dendritic cells (DCs) required for induction of antitumor immune responses and success of cancer immunotherapy. It is established that tumor-associated DCs are defective in their ability to cross-present antigens. However, the mechanisms driving these defects are still unknown. We find that impaired cross-presentation in DCs is largely associated with defect in trafficking of peptide–MHC class I (pMHC) complexes to the cell surface. DCs in tumor-bearing hosts accumulate lipid bodies (LB) containing electrophilic oxidatively truncated (ox-tr) lipids. These ox-tr-LB, but not LB present in control DCs, covalently bind to chaperone heat shock protein 70. This interaction prevents the translocation of pMHC to cell surface by causing the accumulation of pMHC inside late endosomes/lysosomes. As a result, tumor-associated DCs are no longer able to stimulate adequate CD8 T cells responses. In conclusion, this study demonstrates a mechanism regulating cross-presentation in cancer and suggests potential therapeutic avenues.

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Section: Discussionmentioning

confidence: 98%

Lipid bodies containing oxidatively truncated lipids block antigen cross-presentation by dendritic cells in cancer

et al. 2017

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“…Isolation of primary enterocytes was performed as described elsewhere (Khalifeh-Soltani et al, 2016). Briefly, the jejunal segment was washed with Buffer A (115 mM NaCl, 5.4 mM KCl, 0.96 mM NaH 2 PO 4 , 26.19 mM NaHCO 3 , 5.5 mM glucose).…”

Section: Methodsmentioning

confidence: 99%

ATGL/CGI-58-Dependent Hydrolysis of a Lipid Storage Pool in Murine Enterocytes

et al. 2019

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Summary As circulating lipid levels are balanced by the rate of lipoprotein release and clearance from the plasma, lipid absorption in the small intestine critically contributes to the maintenance of whole-body lipid homeostasis. Within enterocytes, excessive triglycerides are transiently stored as cytosolic lipid droplets (cLDs), and their mobilization sustains lipid supply during interprandial periods. Using mice lacking adipose triglyceride lipase (ATGL) and its coactivator comparative gene identification-58 (CGI-58) exclusively in the intestine (intestine-specific double KO [iDKO]), we show that ATGL/CGI-58 are not involved in providing substrates for chylomicron synthesis. Massive intestinal cLD accumulation in iDKO mice independent of dietary lipids together with inefficient lipid incorporation into cLDs in the early absorption phase demonstrate the existence of a secretion/re-uptake cycle, corroborating the availability of two diverse cLD pools. This study identified ATGL/CGI-58 as critical players in the catabolism of basolaterally (blood) derived lipids and highlights the necessity to modify the current model of intestinal lipid metabolism.

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“…In mice, Mfge8 on the enterocyte surface regulates CLD metabolism. In response to a fat challenge, Mfge8 interacts with αvβ3 and αvβ5 integrins to increase intracellular TG hydrolase activity, enhancing CLD TG hydrolysis and CM synthesis 54 . Deficiency in lysophosphatidylcholine acyltransferase-3 (a phospholipid remodeling protein) increases intestinal TG storage and reduces intestinal TG secretion in mice 55, 56, 57.…”

Section: Cld Metabolismmentioning

confidence: 99%

Regulation of Chylomicron Secretion: Focus on Post-Assembly Mechanisms

Xiao

Stahel

Lewis

2019

Cellular and Molecular Gastroenterology and Hepatology

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Dietary fat absorption in the intestine consists of multiple steps, including absorption into enterocytes and intracellular assembly of chylomicrons, chylomicron transport and exit from the enterocytes, movement across the lamina propria, entry into lacteals, and regulated transport in intestinal lymphatics. This review draws attention to postassembly regulation of chylomicron secretion that may present opportunities for improving health. Brief Overview of Dietary Fat Absorption, Chylomicron Biosynthesis, and Secretion Dietary TG digestion starts with TG hydrolysis by lingual lipase in the mouth. In the stomach, gastric lipase and lingual lipase both contribute to TG hydrolysis, especially in the digestion of milk fat in newborns. 8,9 Pancreatic lipase is the major enzyme to catalyze TG hydrolysis in the small

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Mfge8 regulates enterocyte lipid storage by promoting enterocyte triglyceride hydrolase activity

Cited by 34 publications

References 57 publications

Lipid bodies containing oxidatively truncated lipids block antigen cross-presentation by dendritic cells in cancer

Lipid bodies containing oxidatively truncated lipids block antigen cross-presentation by dendritic cells in cancer

ATGL/CGI-58-Dependent Hydrolysis of a Lipid Storage Pool in Murine Enterocytes

Regulation of Chylomicron Secretion: Focus on Post-Assembly Mechanisms

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