Evidence of circadian rhythm in low-density lipoprotein apoB catabolism and its impact on the estimation of kinetic parameters

Background. Compartmental models with constant parameters are commonly used in kinetic analysis of low-density lipoproteins (LDLs). Recent studies in animals have demonstrated the existence of circadian rhythms (CRs) in cholesterol synthesis and LDL catabolism. In this study, we investigated the possible existence of a CR in the fractional catabolic rate (FCR) of LDL apoB in man. Materials and methods. Radioactivity data from 45 turnover studies using ¹²⁵I-labelled LDL apoB were analysed. In a preliminary analysis the pattern of radioactivity decay was investigated. Kinetic analysis was performed by using one- and two-compartment models with constant parameters (steady-state, SS, analysis). Parameters were estimated by the use of the whole data set, which included frequent sampling during the first day of the turnover study, or the once-a-day data, taken at 08.00 h. The selection of once-a-day data allowed elimination of the impact of a CR on parameter evaluation. Furthermore, non-steady-state (NSS) analysis was performed in which the FCR of LDL apoB was calculated as a function of time. In one additional subject, the FCR of LDL apoB was calculated separately for the day and the night using the urine-to-plasma (U/P) radioactivity ratio. Results. The presence of a CR in LDL apoB catabolism, with higher FCR values during the day than during the morning, was demonstrated by the NSS analysis and confirmed by LDL apoB calculation from the U/P ratio. The SS analysis with the whole and the once-a-day data sets resulted in similar average FCR of apoB values (0.329 ± 0.076 and 0.321 ± 0.071 respectively) when the two-compartment model was used. Thus, a CR appeared to have little impact on the average FCR of apoB estimation. However, frequent sampling used in the hope of improving parameter estimation accuracy actually resulted in deterioration of the intercompartmental parameter estimators. Conclusion. The fractional catabolic rate of LDL apoB exhibited a circadian rhythm with higher FCR values during the day than during the morning. The presence of a CR had, however, a limited impact on the overall FCR of apoB values.