Reversible deficits in apical transporter trafficking associated with deficiency in diacylglycerol acyltransferase

Cameron Schlegel, Lynne A. Lapierre, Victoria G. Weis, Janice A. Williams, Izumi Kaji, Carolina Pinzon-Guzman, Nripesh Prasad, Braden Boone, Angela Jones, Hernan Correa, Shawn E. Levy, Xianlin Han, Miao Wang, Kelly Thomsen, Sari Acra, James R. Goldenring

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)879-892
Number of pages14
Issue number11
StatePublished - Nov 2018


  • CLDN4
  • Caco2
  • DGAT1
  • JAM
  • Rab11a
  • diarrhea
  • enterocyte
  • intestine
  • occludin

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Structural Biology
  • Biochemistry
  • Cell Biology


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