title: Postnatal Deletion of Fat Storage-inducing Transmembrane Protein 2 (FIT2/FITM2) Causes Lethal Enteropathy.
abstract: 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 ROSA26CreER(T2)-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.
authors: From the Signature Research Program in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Graduate Medical School, 8 College Road, 169857 Singapore and.
authors: Vera J
authors: VJ
authors: Goh
authors: From the Signature Research Program in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Graduate Medical School, 8 College Road, 169857 Singapore and.
authors: Jolene S Y
authors: JS
authors: Tan
authors: From the Signature Research Program in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Graduate Medical School, 8 College Road, 169857 Singapore and.
authors: Bryan C
authors: BC
authors: Tan
authors: From the Signature Research Program in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Graduate Medical School, 8 College Road, 169857 Singapore and.
authors: Colin
authors: C
authors: Seow
authors: the Department of Anatomy and Neurobiology and Aging Research Programme, National University of Singapore, Singapore 119260, Singapore.
authors: Wei-Yi
authors: WY
authors: Ong
authors: From the Signature Research Program in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Graduate Medical School, 8 College Road, 169857 Singapore and.
authors: Yen Ching
authors: YC
authors: Lim
authors: From the Signature Research Program in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Graduate Medical School, 8 College Road, 169857 Singapore and.
authors: Lei
authors: L
authors: Sun
authors: From the Signature Research Program in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Graduate Medical School, 8 College Road, 169857 Singapore and.
authors: Sujoy
authors: S
authors: Ghosh
authors: From the Signature Research Program in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Graduate Medical School, 8 College Road, 169857 Singapore and david.silver@duke-nus.edu.sg.
authors: David L
authors: DL
authors: Silver
mesh_terms: D000818:Animals; D003643:Death; D017353:Gene Deletion; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D015431:Weight Loss
chemical_list: C526205:FIT2 protein, mouse; D008565:Membrane Proteins
keywords: cell death; intestinal epithelium; lipid droplet; lipoprotein; stem cells