MGAT2-IN-1是一种可口服的单酰甘油酰基转移酶(MGAT2)抑制剂，对人和小鼠MGAT2的IC50值分别为7.8和2.4nM。
MGAT2-IN-1 is an orally active inhibitor of monoacylglycerol acyltransferase (MGAT2) with IC50 of 7.8 and 2.4 nM for human and mouse MGAT2, respectively.
MGAT2-IN-1 (3, 10 mg/kg, p.o.) dose-dependently suppresses plasma TG elevation, and plasma CM/TG AUC in mice. MGAT2-IN-1 does not decrease MG absorption but inhibits MGAT2-dependent TG/DG resynthesis. In the lipid utilization analysis, MGAT2-IN-1 significantly increases free fatty acid (FFA) and acylcarnitine levels. MGAT2-IN-1 (30 mg/kg) also significantly reduces food intake dose dependently, suppresses BW gains. MGAT2-IN-1 shows anti-diabetic effects in mice[1].
[1]. Take K, et al. Pharmacological Inhibition of Monoacylglycerol O-Acyltransferase 2 Improves Hyperlipidemia, Obesity, and Diabetes by Change in Intestinal Fat Utilization. PLoS One. 2016 Mar 3;11(3):e0150976.
Animal experiment: | Mice: Overnight-fasted mice undergo MTT in the morning. First, they are orally administered vehicle (0.5% methylcellulose solution) or MGAT2-IN-1 suspended in 0.5% methylcellulose. Six or 16 h after dosing, they are intraperitoneally injected 500 mg/kg Pluronic F-127 to inhibit plasma TG hydrolysis by lipoprotein lipase (LPL). Thirty minutes after injection, the mice are given an oral liquid meal (10 mL/kg) comprising an admixture of corn oil and Ensure-H (3:17 v/v). Blood samples are collected at 0, 2 and 4 h after oral gavage of the liquid meal. Area under the curve (AUC) of chylomicron TG (CM/TG), which is synthesised from dietary fat in the small intestine, is calculated by subtracting plasma TG levels of a liquid meal-untreated group from plasma TG levels of each treated group. |
参考文献: [1]. Take K, et al. Pharmacological Inhibition of Monoacylglycerol O-Acyltransferase 2 Improves Hyperlipidemia, Obesity, and Diabetes by Change in Intestinal Fat Utilization. PLoS One. 2016 Mar 3;11(3):e0150976. | |
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