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Lipid synthesis and secretion in HepG2 cells is not affected by ACTH

Skoog, Maria LU ; Berggren Söderlund, Maria LU ; Nilsson-Ehle, Peter LU and Xu, Ning LU (2010) In Lipids in Health and Disease 9.
Abstract
Apolipoprotein B (apoB) containing lipoproteins, i.e. VLDL, LDL and Lp(a), are consequently lowered by ACTH treatment in humans. This is also seen as reduced plasma apoB by 20-30% and total cholesterol by 30-40%, mostly accounted for by a decrease in LDL-cholesterol. Studies in hepatic cell line (HepG2) cells showed that apoB mRNA expression is reduced in response to ACTH incubation and is followed by a reduced apoB secretion, which may hypothesize that ACTH lowering apoB containing lipoproteins in humans may be mediated by the inhibition of hepatic apoB synthesis. This was recently confirmed in vivo in a human postprandial study, where ACTH reduced transient apoB48 elevation from the small intestine, however, the exogenic lipid turnover... (More)
Apolipoprotein B (apoB) containing lipoproteins, i.e. VLDL, LDL and Lp(a), are consequently lowered by ACTH treatment in humans. This is also seen as reduced plasma apoB by 20-30% and total cholesterol by 30-40%, mostly accounted for by a decrease in LDL-cholesterol. Studies in hepatic cell line (HepG2) cells showed that apoB mRNA expression is reduced in response to ACTH incubation and is followed by a reduced apoB secretion, which may hypothesize that ACTH lowering apoB containing lipoproteins in humans may be mediated by the inhibition of hepatic apoB synthesis. This was recently confirmed in vivo in a human postprandial study, where ACTH reduced transient apoB48 elevation from the small intestine, however, the exogenic lipid turnover seemed unimpaired. In the present study we investigated if lipid synthesis and/or secretion in HepG2 cells were also affected by pharmacological levels of ACTH to accompany the reduced apoB output. HepG2 cells were incubated with radiolabelled precursors ([C-14] acetate and [H-3] glycerol) either before or during ACTH stimuli. Cellular and secreted lipids were extracted with chloroform: methanol and separated by the thin layer chromatography (TLC), and [C-14] labelled cholesterol and cholesteryl ester and [H-3] labelled triglycerides and phospholipids were quantitated by the liquid scintillation counting. It demonstrated that ACTH administration did not result in any significant change in neither synthesis nor secretion of the studied lipids, this regardless of presence or absence of oleic acid, which is known to stabilize apoB and enhance apoB production. The present study suggests that ACTH lowers plasma lipids in humans mainly mediated by the inhibition of apoB synthesis and did not via the reduced lipid synthesis. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Lipids in Health and Disease
volume
9
publisher
BioMed Central
external identifiers
  • wos:000278383100001
  • scopus:77952139372
ISSN
1476-511X
DOI
10.1186/1476-511X-9-48
language
English
LU publication?
yes
id
0d26bd9f-f405-4f0a-a5ef-c506fde6ac57 (old id 1631834)
date added to LUP
2010-07-21 10:50:24
date last changed
2018-05-29 11:38:58
@article{0d26bd9f-f405-4f0a-a5ef-c506fde6ac57,
  abstract     = {Apolipoprotein B (apoB) containing lipoproteins, i.e. VLDL, LDL and Lp(a), are consequently lowered by ACTH treatment in humans. This is also seen as reduced plasma apoB by 20-30% and total cholesterol by 30-40%, mostly accounted for by a decrease in LDL-cholesterol. Studies in hepatic cell line (HepG2) cells showed that apoB mRNA expression is reduced in response to ACTH incubation and is followed by a reduced apoB secretion, which may hypothesize that ACTH lowering apoB containing lipoproteins in humans may be mediated by the inhibition of hepatic apoB synthesis. This was recently confirmed in vivo in a human postprandial study, where ACTH reduced transient apoB48 elevation from the small intestine, however, the exogenic lipid turnover seemed unimpaired. In the present study we investigated if lipid synthesis and/or secretion in HepG2 cells were also affected by pharmacological levels of ACTH to accompany the reduced apoB output. HepG2 cells were incubated with radiolabelled precursors ([C-14] acetate and [H-3] glycerol) either before or during ACTH stimuli. Cellular and secreted lipids were extracted with chloroform: methanol and separated by the thin layer chromatography (TLC), and [C-14] labelled cholesterol and cholesteryl ester and [H-3] labelled triglycerides and phospholipids were quantitated by the liquid scintillation counting. It demonstrated that ACTH administration did not result in any significant change in neither synthesis nor secretion of the studied lipids, this regardless of presence or absence of oleic acid, which is known to stabilize apoB and enhance apoB production. The present study suggests that ACTH lowers plasma lipids in humans mainly mediated by the inhibition of apoB synthesis and did not via the reduced lipid synthesis.},
  author       = {Skoog, Maria and Berggren Söderlund, Maria and Nilsson-Ehle, Peter and Xu, Ning},
  issn         = {1476-511X},
  language     = {eng},
  publisher    = {BioMed Central},
  series       = {Lipids in Health and Disease},
  title        = {Lipid synthesis and secretion in HepG2 cells is not affected by ACTH},
  url          = {http://dx.doi.org/10.1186/1476-511X-9-48},
  volume       = {9},
  year         = {2010},
}