JTT-553, a novel Acyl CoA:diacylglycerol acyltransferase (DGAT) 1 inhibitor, improves glucose metabolism in diet-induced obesity and genetic T2DM mice

JTT-553 reduced body weight gain and fat weight in diet-induced obesity mice.

• JTT-553 decreased insulin, non-esterified fatty acid, total cholesterol, and liver triglyceride levels in non-fasting DIO mice.
• In DIO mice, JTT-553 improved insulin-dependent glucose uptake in adipose tissues and alleviated glucose intolerance.
• In KK-A(y) mice, JTT-553 lowered glucose, non-esterified fatty acid, total cholesterol, and liver triglyceride levels in both fasting and non-fasting conditions.
• JTT-553 reduced TNF-α mRNA levels while increasing GLUT4 mRNA levels in adipose tissues of KK-A(y) mice.
• These findings indicate potential improvements in insulin resistance and glucose metabolism associated with JTT-553.

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