Dietary fat alters HIV protease inhibitor-induced metabolic changes in mice

Human immunodeficiency virus (HIV) protease inhibitors (PI) may alter lipid metabolism in patients with acquired immunodeficiency syndrome (AIDS). How ever, the influence of dietary fat on the metabolic effects of PI therapy r emains unknown. AKR/J mice were fed high or low fat diets and treated with the PI indinavir (IDV), nelfinavir (NFV), saquinavir (SQV) or amprenavir (A PV) by subcutaneous delivery for 2 wk. Serum concentrations of glucose, ins ulin, triglyceride, free fatty acid, glycerol, pancreatic lipase, bilirubin , alkaline phosphatase, blood urea nitrogen and PI, and interscapular and e pididymal fat weights were determined. Some metabolic effects of PI were de pendent on diet. IDV- and NFV-treated mice had greater serum glucose concen tration and body weight; IDV-treated mice had lower serum insulin; NFV-trea ted mice had greater interscapular fat mass; and SQV treated mice had lower serum triglyceride concentration than control mice fed the low but not the high fat diet. In contrast, NFV- and IDV-treated mice had greater triglyce ride concentration and blood urea nitrogen, and SQV treated mice had greate r serum cholesterol than control mice fed the high but not the low fat diet . The serum concentration of SQV was lower in mice fed the high fat compare d with the low fat diet. Other effects were not dependent on diet. IDV- and NFV-treated mice had greater fatty acids, and IDV-treated mice had greater pancreatic lipase, bilirubin and alkaline phosphatase than control mice fe d either diet. APV treatment had little effect on these serum measurements. Thus, changes in dietary fat can influence some but not all of the effects of PI on metabolism. Furthermore, each PI produces different effects in vi vo, indicating that various PI affect distinct metabolic pathways.