Use of arginine to reduce the severity of retinoid-induced hypertriglyceridemia

Previous research with an animal model of retinoid-induced hypertriglyceridemia, rats fed a 13-cis retinoic acid-containing diet in which casein was the dietary protein, has demonstrated that replacement of dietary casein with soy protein isolate can reduce the severity of this condition. A depressant action of soy protein vs. that of casein on serum triglyceride concentration has also been demonstrated in rats fed purified diets without supplemental retinoid. Because this action of soy protein appears to be due to its having a higher arginine-to-lysine ratio than casein, a study was done to determine how feeding a casein-containing diet supplemented with sufficient arginine, to give a dietary arginine-to-lysine ratio equivalent to that of soy protein, would affect the development of retinoid-induced hypertriglyceridemia. Groups of five-week-old male Fischer 344 rats (n = 7/group) were fed a control diet containing casein or one of three 13-cis retinoic acid-containing diets in which dietary nitrogen was provided as casein, casein + arginine, or soy protein. Incorporation of dietary 13-cis retinoic acid resulted in hypertriglyceridemia, with serum triglyceride concentrations of 2.00 and 7.23 mmol/l, or 177 and 640 mg/dl, for groups fed the control and casein + 13-cis retinoic acid diets, respectively. For animals fed the 13-cis retinoic acid-containing diets, serum triglyceride levels for the casein + arginine and soy protein diet groups (4.75 and 2.92 mmol/l, or 421 and 258 mg/dl, respectively) were significantly lower than for the casein group (p < 0.05); however, the value was significantly lower for the group fed the soy protein diet than for the group fed the casein + arginine diet. Serum and dietary arginine-to-lysine ratios were highly correlated (r = 0.93, p < 0.0001). Thus, supplementing dietary casein with arginine reduced the severity of retinoid-induced hypertriglyceridemia, but not as effectively as replacing casein with soy protein.