Details

Autor(en) / Beteiligte

• Goh, Vera J.
• Tan, Jolene S.Y.
• Tan, Bryan C.
• Seow, Colin
• Ong, Wei-Yi
• Lim, Yen Ching
• Sun, Lei
• Ghosh, Sujoy
• Silver, David L.

Titel

Postnatal Deletion of Fat Storage-inducing Transmembrane Protein 2 (FIT2/FITM2) Causes Lethal Enteropathy

Ist Teil von

• The Journal of biological chemistry, 2015-10, Vol.290 (42), p.25686-25699

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2015

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Lipid droplets (LDs) are phylogenetically conserved cytoplasmic organelles that store neutral lipids within a phospholipid monolayer. LDs compartmentalize lipids and may help to prevent cellular damage caused by their excess or bioactive forms. FIT2 is a ubiquitously expressed transmembrane endoplasmic reticulum (ER) membrane protein that has previously been implicated in LD formation in mammalian cells and tissue. Recent data indicate that FIT2 plays an essential role in fat storage in an in vivo constitutive adipose FIT2 knock-out mouse model, but the physiological effects of postnatal whole body FIT2 depletion have never been studied. Here, we show that tamoxifen-induced FIT2 deletion using a whole body ROSA26CreERT2-driven FIT2 knock-out (iF2KO) mouse model leads to lethal intestinal pathology, including villus blunting and death of intestinal crypts, and loss of lipid absorption. iF2KO mice lose weight and die within 2 weeks after the first tamoxifen dose. At the cellular level, LDs failed to form in iF2KO enterocytes after acute oil challenge and instead accumulated within the ER. Intestinal bile acid transporters were transcriptionally dysregulated in iF2KO mice, leading to the buildup of bile acids within enterocytes. These data support the conclusion that FIT2 plays an essential role in regulating intestinal health and survival postnatally. Background: FIT2 is an ER protein implicated in regulating cytosolic LD formation in mammals. Results: FIT2 deficiency in an inducible whole body knock-out mouse model leads to lethal enteropathy. Conclusion: FIT2 is required for normal intestinal homeostasis and survival. Significance: This study provides evidence that FIT2 is essential for murine intestinal health.