VANADATE INDUCES NORMOLIPIDEMIA AND A REDUCTION IN THE LEVELS OF HEPATIC LIPOGENIC ENZYMES IN OBESE ZUCKER RAT

The effects of vanadate administration on the plasma lipids and hepati c lipogenic enzymes were investigated in Zucker (fa/fa) rat, a model f or obesity and non insulin-dependent diabetes. These animals were admi nistered sodium orthovanadate through drinking water for a period of f our months. The plasma levels of insulin, triacylglycerols and total c holesterol were significantly (p < 0.001) elevated in untreated obese control rats as compared to the lean animals. In the livers of obese r ats, the number of insulin receptors decreased by 60% and the activiti es of lipogenic enzymes acetyl-CoA carboxylase and ATP-citrate lyase i ncreased by 4.7- and 5.6-folds, respectively. The messenger RNA for AT P-citrate lyase as measured by Northern blot analysis showed a paralle l increase in obese control rats. Treatment of these rats with vanadat e caused 56-77% decreases in the plasma levels of insulin, triacylglyc erols and total cholesterol. The insulin receptor numbers in vanadate- treated obese rats increased (119%) compared to levels in untreated ob ese animals. The elevated activities of acetyl-CoA carboxylase and ATP -citrate lyase observed in livers of obese rats were significantly red uced by vanadate. The messenger RNA for ATP-citrate lyase also decreas ed in vanadate-treated obese rats back to the lean control levels. Thi s study demonstrates that vanadate exerts potent actions on lipid meta bolism in diabetic animals in addition to the recognized effects on gl ucose homeostasis.