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Publication
Reversible deficits in apical transporter trafficking associated with deficiency
in diacylglycerol acyltransferase.
Authors Schlegel C, Lapierre LA, Weis VG, Williams JA, Kaji I, Pinzon-Guzman C, Prasad
N, Boone B, Jones A, Correa H, Levy SE, Han X, Wang M, Thomsen K, Acra S,
Goldenring JR
Submitted By Submitted Externally on 11/5/2018
Status Published
Journal Traffic (Copenhagen, Denmark)
Year 2018
Date Published 11/1/2018
Volume : Pages 19 : 879 - 892
PubMed Reference 30095213
Abstract Deficiency in diacylglycerol acyltransferase (DGAT1) is a rare cause of neonatal
diarrhea, without a known mechanism or in vitro model. A patient presenting at
our institution at 7?weeks of life with failure to thrive and diarrhea was found
by whole-exome sequencing to have a homozygous DGAT1 truncation mutation.
Duodenal biopsies showed loss of DGAT1 and deficits in apical membrane
transporters and junctional proteins in enterocytes. When placed on a very
low-fat diet, the patient's diarrhea resolved with normalization of brush border
transporter localization in endoscopic biopsies. DGAT1 knockdown in Caco2-BBe
cells modeled the deficits in apical trafficking, with loss of apical DPPIV and
junctional occludin. Elevation in cellular lipid levels, including
diacylglycerol (DAG) and phospholipid metabolites of DAG, was documented by
lipid analysis in DGAT1 knockdown cells. Culture of the DGAT1 knockdown cells in
lipid-depleted media led to re-establishment of occludin and return of apical
DPPIV. DGAT1 loss appears to elicit global changes in enterocyte polarized
trafficking that could account for deficits in absorption seen in the patient.
The in vitro modeling of this disease should allow for investigation of possible
therapeutic targets.




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