Regulation of mitochondrial sn-glycerol-3-phosphate acyltransferase activity: Response to feeding status is unique in various rat tissues and is discordant with protein expression

Triacylglycerol plays a critical role in an organism's ability to withstand fuel deprivation, and dysregulation of triacylglycerol synthesis is import ant in the development of diseases such as obesity and diabetes. Glycerol-3 -phosphate acyltransferase (GPAT) catalyzes the initial and committed step of glycerolipid synthesis and is therefore a potential site for regulation of triacylglycerol synthesis. Because several studies suggest that triacylg lycerol synthesis is linked to the mitochondrial isoform, we studied mitoch ondrial GPAT expression and the effect of feeding status on the regulation of mitochondrial GPAT in various rat tissues. Liver, adipose, and soleus mu scle have high levels of GPAT mRNA, but low protein expression, whereas hea rt and adrenal, tissues with low GPAT mRNA abundance, have the highest GPAT protein expression. In addition, heart, which has the highest expression o f mitochondrial GPAT protein, has low mitochondrial GPAT specific activity (0.02 nmol/min/ mg). Liver and adipose have the highest mitochondrial GPAT specific activity (0.17 nmol/min/mg), but very low protein expression. Disc repancies between GPAT protein expression and activity suggest that mitocho ndrial GPAT may be regulated acutely. In response to a 48-h fast, liver and adipose mitochondrial GPAT protein expression and activity decrease 30-50% . After 24-h refeeding of either chow or high-sucrose diet, mitochondrial G PAT protein expression and activity overshoot normal levels 30-60%. In kidn ey, mitochondrial GPAT protein and activity increase 65 and 30%, respective ly, with refeeding, whereas in the heart, mitochondrial GPAT activity incre ases 2.3-fold after a fast, with no change in protein expression. We also f ound that hepatic mitochondrial GPAT activity in the neonatal rat constitut es a lower percentage of the total GPAT activity than in the adult. We post ulate that GPAT expression is modulated uniquely in each tissue according t o specific needs for triacylglycerol storage. (C) 2001 Elsevier Science.