Role of MGAT2 and DGAT1 in the release of gut peptides after triglyceride ingestion.
Triglyceride ingestion releases gut peptides from enteroendocrine cells located in the intestinal epithelia and provides feedback regulations of gastrointestinal function. The precise mechanisms sensing lipids in the intestinal wall, however, are not well characterized. In the current study, we investigated the release of gut peptides following oral triglyceride loading in mice deficient for monoacylglycerol acyltransferase 2 (MGAT2KO) and diacylglycerol acyltransferase 1 (DGAT1KO), enzymes that sequentially re-synthesize triglyceride to secrete as chylomicron at the small intestine. In wild-type (Wt) mice, oral triglyceride loading resulted in hypertriglycemia. In addition, plasma glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) were significantly increased 30 min after triglyceride loading, before decaying in 2h. In MGAT2KO and DGAT1KO mice, oral triglyceride loading did not result in hypertriglycemia and the increase in GIP was significantly suppressed in both KO mouse strains. In contrast, the increases in plasma GLP-1 and PYY in both KO mouse strains were comparable to Wt mice 30 min after triglyceride loading, however, they remained elevated in DGAT1KO mice even 2h after triglyceride loading. In parallel to the changes in GLP-1 and PYY, gastric emptying was delayed after oral triglyceride loading in MGAT2KO mice comparably to Wt type mice and was further delayed in DGAT1KO mice. STC-1 and GLUTag, GLP-1-producing intestinal endocrine L-cell lines, displayed a significant level of DGAT1 activity but not MGAT activity. These findings suggest that synthesis and/or secretion of triglyceride-rich lipoproteins play an important role in the release of GIP. Moreover, DGAT1 may directly regulate the release of GLP-1 and PYY in L-cells.
Okawa
Mayumi
M
Tsukuba Research Institute, Banyu Pharmaceutical Company, Ltd, Tsukuba, Ibaraki 300-2611, Japan.
Fujii
Kenji
K
Ohbuchi
Katsuya
K
Okumoto
Mayumi
M
Aragane
Katsumi
K
Sato
Hiromu
H
Tamai
Yoshitaka
Y
Seo
Toru
T
Itoh
Yoshiki
Y
Yoshimoto
Ryo
R
D000217:Acyltransferases / Q000235:genetics / Q000502:physiology*; D000818:Animals; D051048:Diacylglycerol O-Acyltransferase / Q000235:genetics / Q000502:physiology*; D004435:Eating; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D008074:Lipoproteins / Q000096:biosynthesis; D051379:Mice; D018345:Mice, Knockout; D014280:Triglycerides / Q000008:administration & dosage / Q000378:metabolism*
D008074:Lipoproteins; D014280:Triglycerides; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D000217:Acyltransferases; C494882:Dgat1 protein, mouse; D051048:Diacylglycerol O-Acyltransferase; C021802:2-acylglycerol O-acyltransferase