Author:
Skoog Maria,Berggren-Söderlund Maria,Nilsson-Ehle Peter,Xu Ning
Abstract
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 ([14C]acetate and [3H]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 [14C]labelled cholesterol and cholesteryl ester and [3H]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.
Publisher
Springer Science and Business Media LLC
Subject
Biochemistry, medical,Clinical Biochemistry,Endocrinology,Endocrinology, Diabetes and Metabolism
Reference28 articles.
1. Boggaram V, Funkenstein B, Waterman MR, Simpson ER: Lipoproteins and the regulation of adrenal steroidogenesis. Endocr Res. 1984, 10 (3-4): 387-409. 10.1080/07435808409036508
2. Alfano J, Pedersen RC, Kramer RE, Brownie AC: Cholesterol metabolism in the rat adrenal cortex: acute temporal changes following stress. Can J Biochem Cell Biol. 1983, 61 (7): 708-713. 10.1139/o83-089
3. Brunson KL, Avishai-Eliner S, Baram TZ: ACTH treatment of infantile spasms: mechanisms of its effects in modulation of neuronal excitability. Int Rev Neurobiol. 2002, 49: 185-197. full_text
4. Filippini G, Brusaferri F, Sibley WA, Citterio A, Ciucci G, Midgard R, Candelise L: Corticosteroids or ACTH for acute exacerbations in multiple sclerosis. Cochrane Database Syst Rev. 2000, CD001331-4,
5. Berg AL, Nilsson-Ehle P: Direct effects of corticotropin on plasma lipoprotein metabolism in man--studies in vivo and in vitro. Metabolism. 1994, 43 (1): 90-97. 10.1016/0026-0495(94)90162-7
Cited by
3 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献