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

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.
Authors	Hua V Lin, Dunlu Chen, Zhu Shen, Lei Zhu, Xuesong Ouyang, Aurawan Vongs, Yanqing Kan, John M Levorse, Edward J Kowalik Jr, Daphne M Szeto, Xiaorui Yao, Jianying Xiao, Shirley Chen, Jinqi Liu, Marga Garcia-Calvo, Myung K Shin, Shirly Pinto
Journal	PloS one (PLoS One) Vol. 8 Issue 1 Pg. e54480 ( 2013) ISSN: 1932-6203 [Electronic] United States
PMID	23336002 (Publication Type: Journal Article)
Chemical References	Gastrointestinal Hormones Triglycerides Glucagon-Like Peptide 1 Dgat1 protein, mouse Diacylglycerol O-Acyltransferase Dipeptidyl Peptidase 4
Topics	Animals Base Sequence Diacylglycerol O-Acyltransferase (deficiency, genetics, metabolism) Diet Dipeptidyl Peptidase 4 (genetics, metabolism) Dogs Enzyme Activation Female Gastric Emptying (genetics) Gastrointestinal Hormones (metabolism) Gastrointestinal Tract (metabolism) Gene Dosage Gene Expression Regulation Gene Order Genotype Glucagon-Like Peptide 1 (metabolism) Lipid Metabolism Male Mice Mice, Knockout Molecular Sequence Data Postprandial Period Triglycerides (blood)

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