Target intelligence / Profile preview

Diacylglycerol O-acyltransferase 1 (DGAT1) mRNA (DGAT1 mRNA)

Target
DGAT1 mRNA
Molecular classification
mRNA, Enzyme
01

Overview

Diacylglycerol O-acyltransferase 1 (DGAT1) mRNA is the genetic template for the DGAT1 enzyme, which plays a pivotal role in lipid metabolism by catalyzing the final step of triglyceride synthesis (PubMed: 9756920). This enzyme facilitates the covalent bonding of diacylglycerol and fatty acyl-CoA, a process essential for the formation of lipid droplets and the assembly of chylomicrons in the small intestine (UniProt: O75907). By targeting the mRNA transcript, therapeutic agents like antisense oligonucleotides (ASOs) can selectively reduce DGAT1 protein expression, thereby decreasing the systemic availability of triglycerides and potentially improving insulin sensitivity in patients with metabolic syndrome (PubMed: 24510988). Clinical interest in DGAT1 mRNA targeting is driven by its potential to treat obesity, type 2 diabetes, and severe hypertriglyceridemia. However, the reduction of DGAT1 activity, particularly in the intestinal mucosa, is frequently associated with gastrointestinal side effects such as diarrhea and abdominal pain, resulting from the accumulation of undigested lipids (PubMed: 23533141). Current research focuses on optimizing the delivery and dosing of mRNA-targeting therapies to balance metabolic efficacy with patient tolerability.

Other names
DGAT1ARGP1DIAR7Acyl-CoA:diacylglycerol acyltransferase 1Diglyceride acyltransferase 1
02

Mechanism of action

Antisense oligonucleotide-mediated degradation of mRNA to inhibit protein translation

03

Biological functions

Triglyceride synthesisLipid metabolismIntestinal fat absorptionLipid droplet formationChylomicron assembly
04

Disease associations

ObesityType 2 diabetes mellitusHypertriglyceridemiaNonalcoholic fatty liver disease (NAFLD)Familial chylomicronemia syndrome
05

Safety considerations

Gastrointestinal side effects (diarrhea, nausea, vomiting)Fat malabsorptionAbdominal painPotential for hepatic steatosis
06

Interacting drugs

IONIS-DGAT1Rx

1 more in the full profile.

07

Biomarkers

Serum triglyceride levelsBody weightLiver fat contentPostprandial glucose levels

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