Dietary modulation of epidermal protein kinase C: mediation by diacylglycerol

Studies on the mechanism of dietary fat and energy modulation of skin carcinogenesis suggest that these diets may act through the cellular binding site of the phorbol ester tumor promoters, protein kinase C (PKC). High-fat diets increase the activity of PKC but have no impact on the steady-state protein levels. Energy restriction reduces the activity of PKC, presumably through reduction in the steady-state levels of particular isoenzymes (PKC alpha and PKC zeta). Phorbol-binding studies with epidermal cells from mice fed energy-restricted diets indicated a reduction of phorbol-binding sites in these cells. Investigations into lipid metabolism showed that both dietary fat and energy restriction increased epidermal cell diacylglycerol (DAG). The increase in DAG in cells from energy-restricted mice may be due to increased turnover of phosphatidylinositol, as was evident in the reduced phosphatidylinositol-4-phosphate and phosphatidylinositol-4,5-biphosphate and elevated inositol biphosphate and inositol triphosphate in these cells.