Plasma markers of cholesterol homeostasis and apolipoprotein B-100 kinetics in the metabolic syndrome.
OBJECTIVE
The metabolic syndrome is characterized by defective hepatic apolipoprotein B-100 (apoB) metabolism. Hepato-intestinal cholesterol metabolism may contribute to this abnormality.


METHODS
We examined the association of cholesterol absorption and synthesis with the kinetics of apoB in 35 obese subjects with the metabolic syndrome. Plasma ratios of campesterol and lathosterol to cholesterol were used to estimate cholesterol absorption and synthesis, respectively. Very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein apoB kinetics were studied using stable isotopy and mass spectrometry. Kinetic parameters were derived using multicompartmental modeling.


RESULTS
Compared with controls, the obese subjects had significantly lower plasma ratios of campesterol, but higher plasma ratios of lathosterol (p < 0.05 in both). This was associated with elevated VLDL-apoB secretion rate (p < 0.05) and delayed fractional catabolism of IDL and low-density lipoprotein-apoB (p < 0.01). In the obese group, plasma ratios of campesterol correlated inversely with VLDL-apoB secretion (r = -0.359, p < 0.05), VLDL-apoB (r = -0.513, p < 0.01) and IDL-apoB (r = -0.511, p < 0.01) pool size, and plasma lathosterol ratio (r = -0.366, p < 0.05). Subjects with low cholesterol absorption had significantly higher VLDL-apoB secretion, VLDL-apoB and IDL-apoB pool size, and plasma lathosterol ratio (p < 0.05 in both) than those with high cholesterol absorption.


CONCLUSIONS
Subjects with the metabolic syndrome have oversecretion of VLDL-apoB and decreased catabolism of apoB-containing particles and low absorption and high synthesis rates of cholesterol. These changes in cholesterol homeostasis may contribute to the kinetic defects in apoB metabolism in the metabolic syndrome.
Chan
Dick C
DC
School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia.
Watts
Gerald F
GF
Barrett
P Hugh R
PH
O'Neill
Frans H
FH
Thompson
Gilbert R
GR
D000328:Adult; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000097:blood*; D015415:Biomarkers / Q000097:blood*; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000097:blood*; D006706:Homeostasis; D006801:Humans; D007700:Kinetics; D008074:Lipoproteins / Q000097:blood; D053419:Lipoproteins, IDL; D008077:Lipoproteins, LDL / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood*; D008875:Middle Aged; D010840:Phytosterols
D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D015415:Biomarkers; D008074:Lipoproteins; D053419:Lipoproteins, IDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D010840:Phytosterols; C021273:campesterol; C001521:lathosterol; D002784:Cholesterol