High molecular weight adiponectin reduces apolipoprotein B and E release in human hepatocytes.
Low circulating levels of high molecular weight adiponectin (HMW-Apm) have been linked to dyslipidaemia and systemic HMW-Apm negatively correlates with very low density lipoprotein (VLDL), apolipoprotein B (ApoB), and ApoE and is positively associated with ApoA-I. Therefore, it was investigated whether HMW-Apm alters the hepatic synthesis of ApoB, ApoE, and ApoA-I or the activity of the hepatic ATP-binding cassette transporter A1 (ABCA1), as the main determinant of plasma HDL. HMW-Apm reduces hepatic ApoB and ApoE release whereas ABCA1 protein, activity and ApoA-I were not altered. Global gene expression analysis revealed that hepatic nuclear factor 4-alpha (HNF4-alpha) and HNF4-alpha regulated genes like ApoB are downregulated by HMW-Apm and this was confirmed at the mRNA and protein level. Therefore it is concluded that HMW-adiponectin may ameliorate dyslipidaemia by reducing the hepatic release of ApoB and ApoE, whereas ABCA1 function and ApoA-I secretion are not influenced.
Neumeier
Markus
M
Department of Internal Medicine I, Regensburg University Medical Center, D-93042 Regensburg, Germany.
Sigruener
Alexander
A
Eggenhofer
Elke
E
Weigert
Johanna
J
Weiss
Thomas S
TS
Schaeffler
Andreas
A
Schlitt
Hans J
HJ
Aslanidis
Charalampos
C
Piso
Pompiliu
P
Langmann
Thomas
T
Schmitz
Gerd
G
Schölmerich
Jürgen
J
Buechler
Christa
C
D052242:Adiponectin / Q000008:administration & dosage / Q000737:chemistry; D001055:Apolipoproteins B / Q000378:metabolism*; D001057:Apolipoproteins E / Q000378:metabolism*; D002478:Cells, Cultured; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008970:Molecular Weight
C499918:ADIPOQ protein, human; D052242:Adiponectin; D001055:Apolipoproteins B; D001057:Apolipoproteins E