Concerted elevation of acyl-coenzyme A:diacylglycerol acyltransferase (DGAT) activity through independent stimulation of mRNA expression of DGAT1 and DGAT2 by carbohydrate and insulin.
Glucose and insulin are anabolic signals which upregulate the transcriptions of a series of lipogenic enzymes to convert excess carbohydrate into triglycerides for efficient energy storage. These enzymes include ATP-citrate lyase (ACL), acetyl-coenzyme A carboxylase (ACC), fatty acid synthase (FAS), and glycerol-3-phosphate acyltransferase (G3PA). Acyl-coenzyme A:diacylglycerol acyltransferase (DGAT) is important to synthesize fatty acids into triglycerides. Two DGATs from different gene families have recently been identified. In the current study, we report that glucose preferentially enhances DGAT1 mRNA expression, whereas insulin specifically increases the level of DGAT2 mRNA. Treatment of adipocytes with glucose and insulin together results in higher DGAT activity in the membrane than cells treated with either of the agents alone, indicating that glucose and insulin have additive effect on DGAT activation. In mice treated with fast/refeeding protocol, DGAT2 mRNA decreased upon fasting and was replenished upon refeeding in adipose tissue and liver. This pattern of change was not observed for DGAT1. Inasmuch as DGAT1 mRNA is less abundant in liver, we suggest that DGAT1 is more involved in fat absorption in the intestine and in basal level triglyceride synthesis in adipose tissue where it is more highly expressed. In contrast, DGAT2 is more likely to play important roles in assembly of de novo synthesized fatty acids into VLDL particles in the liver.
Meegalla
Rupalie L
RL
Department of Central Nervous System Diseases, Bristol-Myers Squibb Company, Experimental Station, E400/5269, Rt. 141 & Henry Clay Road, Wilmington, DE 19880, USA.
Billheimer
Jeffrey T
JT
Cheng
Dong
D
D016475:3T3 Cells; D000214:Acyl Coenzyme A / Q000378:metabolism*; D000217:Acyltransferases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002241:Carbohydrates / Q000494:pharmacology*; D051048:Diacylglycerol O-Acyltransferase; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D007328:Insulin / Q000494:pharmacology*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D014280:Triglycerides / Q000096:biosynthesis
D000214:Acyl Coenzyme A; D002241:Carbohydrates; D007328:Insulin; D007527:Isoenzymes; D014280:Triglycerides; D000217:Acyltransferases; C494882:Dgat1 protein, mouse; D051048:Diacylglycerol O-Acyltransferase