Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 291-300 |
| Number of pages | 10 |
| Journal | European Journal of Clinical Investigation |
| Volume | 29 |
| Issue number | 4 |
| DOIs | |
| State | Published - 1999 |
| Externally published | Yes |
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Keywords
- Circadian rhythm
- Compartmental model
- Fractional catabolic rate
- Kinetic analysis
- Low-density lipoprotein
- Low-density lipoprotein apoB turnover
ASJC Scopus subject areas
- Medicine(all)
Cite this
Evidence of circadian rhythm in low-density lipoprotein apoB catabolism and its impact on the estimation of kinetic parameters. / Weryński, A.; Nahorski, Z.; Berglund, Lars; Ericsson, S.; Angelin, B.; Eriksson, M.
In: European Journal of Clinical Investigation, Vol. 29, No. 4, 1999, p. 291-300.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Evidence of circadian rhythm in low-density lipoprotein apoB catabolism and its impact on the estimation of kinetic parameters
AU - Weryński, A.
AU - Nahorski, Z.
AU - Berglund, Lars
AU - Ericsson, S.
AU - Angelin, B.
AU - Eriksson, M.
PY - 1999
Y1 - 1999
N2 - 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.
AB - 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.
KW - Circadian rhythm
KW - Compartmental model
KW - Fractional catabolic rate
KW - Kinetic analysis
KW - Low-density lipoprotein
KW - Low-density lipoprotein apoB turnover
UR - http://www.scopus.com/inward/record.url?scp=0032896251&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032896251&partnerID=8YFLogxK
U2 - 10.1046/j.1365-2362.1999.00453.x
DO - 10.1046/j.1365-2362.1999.00453.x
M3 - Article
C2 - 10231341
AN - SCOPUS:0032896251
VL - 29
SP - 291
EP - 300
JO - European Journal of Clinical Investigation
JF - European Journal of Clinical Investigation
SN - 0014-2972
IS - 4
ER -