DIETARY POLYUNSATURATED TO SATURATED FATTY-ACID RATIO ALTERS HEPATIC LDL TRANSPORT IN CYNOMOLGUS MACAQUES FED LOW CHOLESTEROL DIETS

To determine effect of interaction between dietary cholesterol and triglyceride, i.e., polyunsaturated to saturated (P:S) fatty acid ratio, on LDL metabolism, male cynomolgus macaques were fed purified diets for 83 wk with cholesterol levels of 0.01, 0.06 and 0.50 mg/kJ and P:S ratios of 0.5 and 0.9, oleic acid constant. There were six groups of five animals each (cholesterol, mg/kJ-P:S ratio): Group 1, 0.01-0.5; Group 2, 0.01-0.9; Group 3, 0.06-0.5; Group 4, 0.06-0.9; Group 5, 0.50-0.5; Group 6, 0.50-0.9. LDL (1.019 < d < 1.063 kg/L) and glucosylated LDL were iodinated for turnover studies. Hepatic LDL transport was determined using I-125-tyramine-cellobiose-LDL as tracer. Plasma cholesterol increased in proportion to dietary cholesterol, and concentrations (mmol/L) at 77-78 wk were (mean +/-SEM): Group 1, 434 +/- 0.3 1; Group 2, 3.03 +/- 0.14; Group 3, 8.28 +/- 1.48; Group 4, 7.34 +/- 1.31; Group 5, 15.54 +/-1.44; Group 6, 15.54 +/- 1.41. LDL cholesterol was 45% higher in Group 1 (2.43 mmol/L) than in Group 2 (1.68 mmol/L). In vivo studies showed that LDL clearance was suppressed by excess dietary cholesterol; receptor-independent LDL clearance was relatively constant. Hepatic LDL protein transport was greater in Group 2 (P: S 0.9) compared with Group 1 (P:S 0.5). The LDL protein synthetic rate was lower in Groups 2, 4 and 6 (P: S 0.9) relative to Groups 1, 3 and 5 (P:S 0.5). We conclude that in this model hepatic LDL receptor activity is altered by degree of saturation in dietary triglycerides when dietary cholesterol is minimal, and that saturated dietary triglycerides enhance LDL protein secretion when dietary cholesterol is ample.