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Home > References > 2013 > Diacylglycerol Acyltransferase-1 (DGAT1) inhibition perturbs postprandial gut hormone release.

Diacylglycerol Acyltransferase-1 (DGAT1) inhibition perturbs postprandial gut hormone release.

Lin HV, Chen D, Shen Z, Zhu L, Ouyang X, Vongs A, Kan Y, Levorse JM, Kowalik EJ Jr, Szeto DM, Yao X, Xiao J, Chen S, Liu J, Garcia-Calvo M, Shin MK, Pinto S.
Journal   PLoS One
Species  
Analytes Measured   GLP-1
Matrix Tested   Plasma
Year   2013
Volume   8
Page Numbers   54480
Application   Metabolic
Abstract
Diacylglycerol acyltransferase-1 (DGAT1) is a potential therapeutic target for treatment of obesity and related metabolic diseases. However, the degree of DGAT1 inhibition required for metabolic benefits is unclear. Here we show that partial DGAT1 deficiency in mice suppressed postprandial triglyceridemia, led to elevations in glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) only following meals with very high lipid content, and did not protect from diet-induced obesity. Maximal DGAT1 inhibition led to enhanced GLP-1 and PYY secretion following meals with physiologically relevant lipid content. Finally, combination of DGAT1 inhibition with dipeptidyl-peptidase-4 (DPP-4) inhibition led to further enhancements in active GLP-1 in mice and dogs. The current study suggests that targeting DGAT1 to enhance postprandial gut hormone secretion requires maximal inhibition, and suggests combination with DPP-4i as a potential strategy to develop DGAT1 inhibitors for treatment of metabolic diseases.

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