scholarly journals Measurement of Steroid Fatty Acyl Esters in Blood and Brain

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A811-A812
Author(s):  
Sofia L Gray ◽  
Cecilia Jalabert ◽  
Chunqi Ma ◽  
Kiran K Soma

Abstract Steroid fatty acyl esters (FAEs) are a class of steroid conjugates that are abundant in circulation, have long half-lives, and are stored in lipid-rich tissues. Steroid-FAEs are present in many species, but their functions are poorly understood. They can be metabolized to active, unconjugated steroids and therefore may act as a reservoir of steroids. Dehydroepiandrosterone (DHEA) is an androgen precursor that can be conjugated to various fatty acids. DHEA also modulates aggression in several species, including songbirds, rodents and humans. Recent studies suggest that DHEA-FAEs might be present in songbird blood and/or brain, in part, to regulate aggression. Here, we (1) investigated the abundance of multiple fatty acids in songbird blood and (2) developed an indirect method to measure DHEA-FAEs in songbird blood and brain. First, preliminary work demonstrated high circulating levels of total (esterified and non-esterified) fatty acids, especially oleic, linoleic, and palmitic acids. These data, in conjunction with previous research, suggest that these fatty acids might be conjugated to steroids, including DHEA. Second, we successfully developed a saponification technique to indirectly measure DHEA-FAEs. Saponification cleaves the bond between the steroid molecule and the fatty acid, and we then measure the unconjugated steroid. DHEA-FAEs were incubated in 0.5M potassium hydroxide in ethanol for 30 min at room temperature, and steroids were subsequently extracted twice with dichloromethane. Unconjugated DHEA was quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS), the gold standard in steroid measurement. DHEA recovery was 88% using reference standards in neat solution. We validated this method with song sparrow plasma and chicken serum and obtained recoveries of 94-105% with intra-assay variation of 2.6%. Future research will directly measure specific DHEA-FAEs (e.g. DHEA-oleate) in blood and brain using LC-MS/MS. This research will elucidate the possible roles of steroid-FAEs in brain function and the regulation of steroid-dependent behavior. This work may also clarify the identities, levels and functions of steroid-FAEs in other species, including rodent models and humans. These data have implications for basic and clinical neuroendocrinology, offering insights into a possible storage system for steroids that may influence social behaviour.

1984 ◽  
Vol 62 (11) ◽  
pp. 1134-1150 ◽  
Author(s):  
P. M. Macdonald ◽  
B. D. Sykes ◽  
R. N. McElhaney

The orientational order parameters of monofluoropalmitic acids biosynthetically incorporated into membranes of Acholeplasma laidlawii B in the presence of a large excess of a variety of structurally diverse fatty acids have been determined via 19F nuclear magnetic resonance (19F NMR) spectroscopy. It is demonstrated that these monofluoropalmitic acids are relatively nonperturbing membrane probes based upon physical (differential scanning calorimetry), biochemical (membrane lipid analysis), and biological (growth studies) criteria. 19F NMR is shown to convey the same qualitative and quantitative picture of membrane lipid order provided by 2H-NMR techniques and to be sensitive to the structural characteristics of the membrane fatty acyl chains, as well as to the lipid phase transition. Representatives of each naturally occurring class of fatty acyl chain structures, including straight-chain saturated, methyl-branched, monounsaturated, and alicyclic-ring-substituted fatty acids, were studied and the 19F-NMR order parameters were correlated with the lipid phase transitions (determined calorimetrically). The lipid phase transition was the prime determinant of overall orientational order regardless of fatty acid structure. Effects upon orientational order attributable to specific structural substituents were discernible, but were secondary to the effects of the lipid phase transition. In the gel state, relative overall order was directly proportional to the temperature of the particular lipid phase transition. Not only the overall order, but also the order profile across the membrane was sensitive to the presence of particular structural substituents. In particular, in the gel state specific fatty acyl structures demonstrated a characteristic disordering effect in the membrane order profile. These various observations can be merged to provide a unified picture of the manner in which fatty acyl chain chemistry modulates the physical state of membrane lipids.


2007 ◽  
Vol 70 (5) ◽  
pp. 1206-1212 ◽  
Author(s):  
CLELIA ALTIERI ◽  
DANIELA CARDILLO ◽  
ANTONIO BEVILACQUA ◽  
MILENA SINIGAGLIA

The antifungal activity of three fatty acids (lauric, myristic, and palmitic acids) and their monoglycerides (monolaurin, monomyristic acid, and palmitin, respectively) against Aspergillus and Penicillium species in a model system was investigated. Data were modeled through a reparameterized Gompertz equation. The maximum colony diameter attained within the experimental time (30 days), the maximal radial growth rate, the lag time (i.e., the number of days before the beginning of radial fungal growth), and the minimum detection time (MDT; the number of days needed to attain 1 cm colony diameter) were evaluated. Fatty acids and their monoglycerides inhibited mold growth by increasing MDT and lag times. The effectiveness of the active compounds seemed to be strain and genus dependent. Palmitic acid was the most effective chemical against aspergilli, whereas penicilli were strongly inhibited by myristic acid. Aspergilli also were more susceptible to fatty acids than were penicilli, as indicated by the longer MDT.


2016 ◽  
Vol 9 ◽  
pp. NMI.S39043 ◽  
Author(s):  
Salma A. Abdelmagid ◽  
Jessica L. MacKinnon ◽  
Sarah M. Janssen ◽  
David W.L. Ma

Diet and exercise are recognized as important lifestyle factors that significantly influence breast cancer risk. In particular, dietary n-3 polyunsaturated fatty acids (PUFAs) have been shown to play an important role in breast cancer prevention. Growing evidence also demonstrates a role for exercise in cancer and chronic disease prevention. However, the potential synergistic effect of n-3 PUFA intake and exercise is yet to be determined. This review explores targets for breast cancer prevention that are common between n-3 PUFA intake and exercise and that may be important study outcomes for future research investigating the combined effect of n-3 PUFA intake and exercise. These lines of evidence highlight potential new avenues for research and strategies for breast cancer prevention.


2001 ◽  
Vol 281 (6) ◽  
pp. G1333-G1339 ◽  
Author(s):  
Janardan K. Reddy

Peroxisomes are involved in the β-oxidation chain shortening of long-chain and very-long-chain fatty acyl-CoAs, long-chain dicarboxylyl-CoAs, the CoA esters of eicosanoids, 2-methyl-branched fatty acyl-CoAs, and the CoA esters of the bile acid intermediates, and in the process, they generate H2O2. There are two complete sets of β-oxidation enzymes present in peroxisomes, with each set consisting of three distinct enzymes. The classic PPARα-regulated and inducible set participates in the β-oxidation of straight-chain fatty acids, whereas the second noninducible set acts on branched-chain fatty acids. Long-chain and very-long-chain fatty acids are also metabolized by the cytochrome P-450 CYP4A ω-oxidation system to dicarboxylic acids that serve as substrates for peroxisomal β-oxidation. Evidence derived from mouse models of PPARα and peroxisomal β-oxidation deficiency highlights the critical importance of the defects in PPARα-inducible β-oxidation in energy metabolism and in the development of steatohepatitis.


2013 ◽  
Vol 16 (2) ◽  
pp. 160-174 ◽  
Author(s):  
Debra Lyon ◽  
Lynne Elmore ◽  
Noran Aboalela ◽  
Jacqueline Merrill-Schools ◽  
Nancy McCain ◽  
...  

Due to recent treatment advances, there have been improvements in the proportion of women surviving a diagnosis of breast cancer (BC). However, many of these survivors report persistent adverse side effects following treatment, such as cognitive dysfunction, depressive symptoms, anxiety, fatigue, sleep disturbances, and pain. Investigators have examined circulating levels of inflammatory markers, particularly serum cytokines, for a potential causal relationship to the development/persistence of these psychoneurological symptoms (PNS). While inflammatory activation, resulting from perceived stress or other factors, may directly contribute to the development of PNS, we offer an alternative hypothesis, suggesting that these symptoms are an early step in a cascade of biological changes leading to epigenetic alterations at the level of deoxyribonucleic acid (DNA) methylation, histone modifications, and/or chromatin structure/chromosomal instability. Given that epigenetic patterns have plasticity, if this conjectured relationship between epigenomic/acquired genomic alterations and the development/persistence of PNS is confirmed, it could provide foundational knowledge for future research leading to the recognition of predictive markers and/or treatments to alleviate PNS in women with BC. In this article, we discuss an evolving theory of the biological basis of PNS, integrating knowledge related to inflammation and DNA repair in the context of genetic and epigenetic science to expand the paradigm for understanding symptom acquisition/persistence following chemotherapy.


Blood ◽  
1996 ◽  
Vol 87 (4) ◽  
pp. 1377-1384 ◽  
Author(s):  
PK Schick ◽  
J Walker

The acylation of megakaryocyte proteins was studied with special emphasis on the myristoylation and palmitoylation of the glycoprotein (GP) Ib complex. Guinea pig megakaryocytes were purified and separated into subpopulations at different phases of maturation. Cells were incubated with [3H]myristate, [3H]palmitate, or [3H]acetate to study endogenous protein acylation. Cycloheximide was used to distinguish between cotranslational and posttranslational acylation and hydroxylamine to distinguish between thioester and amide linkages. After incubations, delipidated proteins or GPIb complex subunits, immunoprecipitated with PG-1, AN-51 or FMC-25 monoclonal antibody, were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and assessed by fluorography. Radiolabeled fatty acids bound to GPIX and GPIb were also analyzed by high pressure liquid chromatography (HPLC) and scintillation spectrometry. With [3H]myristic acid and [3H]acetate, GPIX was found to be a major myristoylated protein in megakaryocytes and CHRF-288 cells. Myristic acid was linked to GPIX by an amide bond, and this process occurred cotranslationally. With [3H]acetate, GPIb was primarily palmitoylated, but with [3H]myristate, GPIb was acylated with about equal mounts of myristic acid and palmitic acids. Both fatty acids were linked to GPIb by thioester bonds, and acylation was posttranslational. The myristoylation of GPIX while the palmitoylation of GPIb occurred throughout megakaryocyte maturation. Myristoylation and palmitoylation may have different functions relevant to the assembly of the GPIb complex in megakaryocytes.


Sign in / Sign up

Export Citation Format

Share Document