HEPATIC PROTEIN-KINASE-C IS NOT ACTIVATED DESPITE HIGH INTRACELLULAR 1,2-SN-DIACYLGLYCEROL IN OBESE ZUCKER RATS

High intracellular 1,2,-sn-diacylglycerol (DAG) usually activates prot ein kinase C (PKC). In choline-deficient Fischer 344 rats. we previous ly showed that fatty liver was associated with elevated hepatic DAG an d sustained activation of PKC. Steatosis is a sequelae of many liver t oxins, and we wanted to determine whether fatty liver is always associ ated with accumulation of DAG with activation of PKC. Obese Zucker rat s had 1 I-fold more triacylglycerol in their livers and 2-fold more DA G in their hepatic plasma membrane than did lean control Zucker rats. However, this increased diacylglycerol was not associated with translo cation or activation of PKC in hepatic plasma membrane (activity in ob ese rats was 897 pmol/mg protein X min(-1) vs. 780 pmol/mg protein X m in(-1) in lean rats). No differences in PKC isoform expression were de tected between obese and lean rats. In additional studies, we found th at choline deficiency in the Zucker rat did not result in activation o f PKC in liver, unlike our earlier observations in the choline deficie nt Fischer rat. This dissociation between fatty liver, DAG accumulatio n and PKC activation in Zucker rats supports previous reports of abnor malities in PKC signaling in this strain of rats. (C) 1997 Elsevier Sc ience B.V.