scholarly journals Tissue-Specific Ablation of ACSL4 Results in Disturbed Steroidogenesis

Endocrinology ◽  
2019 ◽  
Vol 160 (11) ◽  
pp. 2517-2528 ◽  
Author(s):  
Wei Wang ◽  
Xiao Hao ◽  
Lina Han ◽  
Zhe Yan ◽  
Wen-Jun Shen ◽  
...  

Abstract ACSL4 is a member of the ACSL family that catalyzes the conversion of long-chain fatty acids to acyl-coenzyme As, which are essential for fatty-acid incorporation and utilization in diverse metabolic pathways, including cholesteryl ester synthesis. Steroidogenic tissues such as the adrenal gland are particularly enriched in cholesteryl esters of long-chain polyunsaturated fatty acids, which constitute an important pool supplying cholesterol for steroid synthesis. The current studies addressed whether ACSL4 is required for normal steroidogenesis. CYP11A1 promoter‒mediated Cre was used to generate steroid tissue‒specific ACSL4 knockout (KO) mice. Results demonstrated that ACSL4 plays an important role in adrenal cholesteryl ester formation, as well as in determining the fatty acyl composition of adrenal cholesteryl esters, with ACSL4 deficiency leading to reductions in cholesteryl ester storage and alterations in cholesteryl ester composition. Statistically significant reductions in corticosterone and testosterone production, but not progesterone production, were observed in vivo, and these deficits were accentuated in ex vivo and in vitro studies of isolated steroid tissues and cells from ACSL4-deficient mice. However, these effects on steroid production appear to be due to reductions in cholesteryl ester stores rather than disturbances in signaling pathways. We conclude that ACSL4 is dispensable for normal steroidogenesis.

2018 ◽  
Vol 5 (12) ◽  
pp. 181483 ◽  
Author(s):  
Lauren E. Jamieson ◽  
Angela Li ◽  
Karen Faulds ◽  
Duncan Graham

Raman spectroscopy has been used extensively for the analysis of biological samples in vitro , ex vivo and in vivo . While important progress has been made towards using this analytical technique in clinical applications, there is a limit to how much chemically specific information can be extracted from a spectrum of a biological sample, which consists of multiple overlapping peaks from a large number of species in any particular sample. In an attempt to elucidate more specific information regarding individual biochemical species, as opposed to very broad assignments by species class, we propose a bottom-up approach beginning with a detailed analysis of pure biochemical components. Here, we demonstrate a simple ratiometric approach applied to fatty acids, a subsection of the lipid class, to allow the key structural features, in particular degree of saturation and chain length, to be predicted. This is proposed as a starting point for allowing more chemically and species-specific information to be elucidated from the highly multiplexed spectrum of multiple overlapping signals found in a real biological sample. The power of simple ratiometric analysis is also demonstrated by comparing the prediction of degree of unsaturation in food oil samples using ratiometric and multivariate analysis techniques which could be used for food oil authentication.


2011 ◽  
Vol 70 (OCE3) ◽  
Author(s):  
C. J. Harden ◽  
A. N. Jones ◽  
T. Maya-Jimenez ◽  
M. E. Barker ◽  
N. J. Hepburn ◽  
...  

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Mariya Misheva ◽  
Konstantinos Kotzamanis ◽  
Luke C. Davies ◽  
Victoria J. Tyrrell ◽  
Patricia R. S. Rodrigues ◽  
...  

AbstractOxylipins are potent biological mediators requiring strict control, but how they are removed en masse during infection and inflammation is unknown. Here we show that lipopolysaccharide (LPS) dynamically enhances oxylipin removal via mitochondrial β-oxidation. Specifically, genetic or pharmacological targeting of carnitine palmitoyl transferase 1 (CPT1), a mitochondrial importer of fatty acids, reveal that many oxylipins are removed by this protein during inflammation in vitro and in vivo. Using stable isotope-tracing lipidomics, we find secretion-reuptake recycling for 12-HETE and its intermediate metabolites. Meanwhile, oxylipin β-oxidation is uncoupled from oxidative phosphorylation, thus not contributing to energy generation. Testing for genetic control checkpoints, transcriptional interrogation of human neonatal sepsis finds upregulation of many genes involved in mitochondrial removal of long-chain fatty acyls, such as ACSL1,3,4, ACADVL, CPT1B, CPT2 and HADHB. Also, ACSL1/Acsl1 upregulation is consistently observed following the treatment of human/murine macrophages with LPS and IFN-γ. Last, dampening oxylipin levels by β-oxidation is suggested to impact on their regulation of leukocyte functions. In summary, we propose mitochondrial β-oxidation as a regulatory metabolic checkpoint for oxylipins during inflammation.


1985 ◽  
Vol 226 (1) ◽  
pp. 319-322 ◽  
Author(s):  
D C K Roberts ◽  
N E Miller ◽  
S G L Price ◽  
D Crook ◽  
C Cortese ◽  
...  

A simple method has been developed for labelling human plasma lipoproteins to high specific radioactivity with radioactive cholesteryl esters in vitro. After isolation by preparative ultracentrifugation, the selected lipoprotein was incubated for 30 min at 4 degrees C in human serum (d greater than 1.215) that had been prelabelled with [4-14C]cholesteryl oleate or [1,2-3H]cholesteryl linoleate, and was then re-isolated by ultracentrifugation. All major lipoprotein classes were labelled by the procedure. Specific radioactivities of up to 18 d.p.m. pmol-1 (46 d.p.m. ng-1) were achieved. When radiolabelled high-density lipoprotein was infused intravenously, the radioactive cholesteryl ester behaved in vivo indistinguishably from endogenous cholesteryl esters produced by the lecithin (phosphatidylcholine): cholesterol acyltransferase reaction.


1997 ◽  
Vol 1997 ◽  
pp. 129-129
Author(s):  
M.D. Carro ◽  
E.L. Miller ◽  
O.C. Fabb

In one in vitro study Ashes et al. (1992) reported that C20 and C22 fatty acids (FA) from fish oil were not hydrogenated to any significant extent by rumen microorganisms. However, to our knowledge, no measurement on hydrogenation has been performed on fishmeal (FM) FA. The aim of this experiment was to study the in vivo and in situ rumen hydrogenation of long-chain FA of two different FM: FMl (60 g FA/g DM) and FM2 (85 g FA/g DM).Six sheep fitted with rumen cannulae and single duodenal cannulae were fed every 2 hours, receiving 1 kg/d of a 60:40 hay:concentrate diet, either alone (Control; C) or supplemented with 40 g FM/d (FMl and FM2). The experiment was carried out over four periods (two sheep received one of the diets in each period) and Cr-NDF was used as a marker to estimate duodenal flow. Data were subjected to analysis of variance using the ANOVA procedure of the Statistical Analysis Systems (SAS, 1994).


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