© 2000 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Leptin, Peroxisome Proliferator-Activated Receptor-
, and CCAAT/Enhancer Binding Protein-
mRNA Expression in Adipose Tissue of Humans and Their Relation to Cardiovascular Risk Factors
From the Departments of Internal Medicine (F.K.) and Surgery (E.H.), Krankenhaus Hallein; and the Departments of Laboratory Medicine (D.B., H.O., H.E., W.P.) and Internal Medicine (B.P.), Landeskrankenanstalten, Salzburg, Austria.
Correspondence to Franz Krempler, MD, Department of Internal Medicine, Krankenhaus Hallein, Bürgermeisterstraße 34, A-5400 Hallein, Austria. E-mail w.patsch{at}lkasbg.gv.at
Abstract—Obesity is a prevalent
disorder that increases the risk for premature
cardiovascular disease. The adipose tissue itself plays
an active role in the regulation of fuel metabolism and
energy homeostasis by expressing a number of regulatory genes, such as
leptin, peroxisome proliferator–activated receptor-
(PPAR), and CCAAT/enhancer binding protein-
(C/EBP). To study
the in vivo relationships among these genes and their associations with
cardiovascular risk factors, plasma levels of leptin,
lipids, apolipoproteins (apo), insulin, and glucose were measured in
216 obese, 165 nonobese, and 36 weight-losing postobese subjects. mRNA
expression of leptin, PPAR, and C/EBP in the extraperitoneal and
intraperitoneal adipose tissue was quantified in
subsets of subjects. In obese individuals, plasma leptin was associated
with apoA-I (r=0.2346, P<0.001) and
insulin (r=0.2125, P<0.002). Leptin and
C/EBP mRNA expression in extraperitoneal and
intraperitoneal adipose tissue of obese patients
was higher than in the respective tissues of nonobese or postobese
subjects. No significant differences among the study groups were found
for PPAR mRNA expression. Leptin, PPAR, and C/EBP mRNA levels
correlated with each other in the intraperitoneal
and extraperitoneal fat of obese subjects, but
multivariate analysis revealed that only
C/EBP was a predictor of leptin expression in extraperitoneal tissue
(partial r=0.6096, P<0.001).
Intraperitoneal PPAR expression was inversely
related to fasting insulin (r=-0.2888,
P<0.017) and a fasting insulin resistance index
(r=-0.2814, P<0.021) in obese subjects.
In postobese patients, intraperitoneal PPAR
expression was associated with plasma HDL cholesterol
(r=0.5695, P<0.018) and apoA-I
(r=0.6216, P<0.008) but was inversely
related to LDL cholesterol (r=-0.5101,
P<0.03) and apoB (r=-0.6331,
P<0.007). These findings suggest a relationship between
plasma leptin and HDL metabolism as well as adipose-tissue
site–dependent associations among leptin, C/EBP-, and PPAR- mRNA
expression. Furthermore, our results suggest that C/EBP- enhances
leptin expression in vivo and that PPAR mRNA expression is inversely
associated with cardiovascular risk factors.
Key Words: leptin • peroxisome proliferator–activated receptor- • CCAAT • enhancer binding protein- • obesity • cardiovascular risk
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