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Frontiers in Physiology 2022Acyl-ghrelin (AG) is an orexigenic hormone that has a unique octanoyl modification on its third serine residue. It is often referred to as the "hunger hormone" due to... (Review)
Review
Acyl-ghrelin (AG) is an orexigenic hormone that has a unique octanoyl modification on its third serine residue. It is often referred to as the "hunger hormone" due to its involvement in stimulating food intake and regulating energy homeostasis. The discovery of the enzyme ghrelin-O-acyltransferase (GOAT), which catalyses ghrelin acylation, provided further insights into the relevance of this lipidation process for the activation of the growth hormone secretagogue receptor (GHS-R) by acyl-ghrelin. Although acyl-ghrelin is predominantly linked with octanoic acid, a range of saturated fatty acids can also bind to ghrelin possibly leading to specific functions. Sources of ghrelin acylation include beta-oxidation of longer chain fatty acids, with contributions from fatty acid synthesis, the diet, and the microbiome. In addition, both acyl-ghrelin and unacyl-ghrelin (UAG) have feedback effects on lipid metabolism which in turn modulate their levels. Recently we showed that whilst acyl-ghrelin promotes adult hippocampal neurogenesis and enhances memory function, UAG inhibits these processes. As a result, we postulated that the circulating acyl-ghrelin:unacyl-ghrelin (AG:UAG) ratio might be an important regulator of neurogenesis and cognition. In this review, we discuss emerging evidence behind the relevance of ghrelin acylation in the context of brain physiology and pathology, as well as the current challenges of identifying the provenance of the acyl moiety.
PubMed: 35845996
DOI: 10.3389/fphys.2022.831641 -
Scientific Reports Mar 2021Octanoic acid is a medium-chained saturated fatty acid found abundantly in the ketogenic dietary supplements containing medium chained triglycerides (MCT) along with...
Octanoic acid is a medium-chained saturated fatty acid found abundantly in the ketogenic dietary supplements containing medium chained triglycerides (MCT) along with decanoic acid. The MCT ketogenic diet is commonly consumed for weight loss but has also showcased neuroprotective potential against neurodegenerative disorders. However, recent clinical findings have reported a critical disadvantage with the long-term consumption of ketogenic diet i.e. bone loss. The following study was employed to investigate whether the two major components of MCT diet also possess bone loss potential as observed with classical ketogenic diet. Swiss albino mice aged between 10 and 12 weeks, were divided into 3 treatment groups that were administered with oral suspensions of octanoic acid, decanoic acid and a combination of both for 4 weeks. Bone specific markers, microarchitectural parameters, using micro computed tomography, and biomechanical strength were analyzed. Remarkably deleterious alterations in the trabecular bone microarchitecture, and on bone markers were observed in the octanoic acid treated groups. Our results suggest significant negative effects on bone health by octanoic acid. These findings require further investigation and validation in order to provide significant clinically relevant data to possibly modify dietary composition of the MCT ketogenic diet.
Topics: Animals; Biomechanical Phenomena; Bone Density; Bone Resorption; Cancellous Bone; Caprylates; Decanoic Acids; Diet, High-Protein Low-Carbohydrate; Diet, Ketogenic; Dietary Supplements; Femur; Ketone Bodies; Male; Mice; Neuroprotective Agents; Osteoclasts; Random Allocation; Tibia; Triglycerides
PubMed: 33772066
DOI: 10.1038/s41598-021-86468-9 -
BMC Biology Feb 2022In insects, airborne chemical signals are mainly detected by two receptor families, odorant receptors (ORs) and ionotropic receptors (IRs). Functions of ORs have been...
BACKGROUND
In insects, airborne chemical signals are mainly detected by two receptor families, odorant receptors (ORs) and ionotropic receptors (IRs). Functions of ORs have been intensively investigated in Diptera and Lepidoptera, while the functions and evolution of the more ancient IR family remain largely unexplored beyond Diptera.
RESULTS
Here, we identified a repertoire of 26 IRs from transcriptomes of female and male antennae, and ovipositors in the moth Agrotis segetum. We observed that a large clade formed by IR75p and IR75q expansions is closely related to the acid-sensing IRs identified in Diptera. We functionally assayed each of the five AsegIRs from this clade using Xenopus oocytes and found that two receptors responded to the tested ligands. AsegIR75p.1 responded to several compounds but hexanoic acid was revealed to be the primary ligand, and AsegIR75q.1 responded primarily to octanoic acid, and less so to nonanoic acid. It has been reported that the C-C medium-chain fatty acids repel various insects including many drosophilids and mosquitos. We show that the C-C medium-chain fatty acids elicited antennal responses of both sexes of A. segetum, while only octanoic acid had repellent effect to the moths in a behavioral assay. In addition, using fluorescence in situ hybridization, we demonstrated that the five IRs and their co-receptor AsegIR8a are not located in coeloconic sensilla as found in Drosophila, but in basiconic or trichoid sensilla.
CONCLUSIONS
Our results significantly expand the current knowledge of the insect IR family. Based on the functional data in combination with phylogenetic analysis, we propose that subfunctionalization after gene duplication plays an important role in the evolution of ligand specificities of the acid-sensing IRs in Lepidoptera.
Topics: Animals; Arthropod Antennae; Brassica napus; Caprylates; Diptera; Female; In Situ Hybridization, Fluorescence; Insect Proteins; Ligands; Male; Moths; Phylogeny; Receptors, Odorant
PubMed: 35130883
DOI: 10.1186/s12915-022-01235-0 -
Nutrients Dec 2022Medium-chain fatty acids contain 6-12 carbon atoms and are absorbed directly into the blood vessels, proceeding to the portal vein and, finally, to the liver, where...
Medium-chain fatty acids contain 6-12 carbon atoms and are absorbed directly into the blood vessels, proceeding to the portal vein and, finally, to the liver, where they are immediately utilized for energy. We aimed to determine the medium-chain fatty acid levels in women with and without breast cancer. A total of 200 women (100 breast cancer subjects and 100 control subjects) were recruited for the study as per the inclusion and exclusion criteria. Blood samples were collected for biochemical estimations. Fatty acid methyl esters were isolated, and medium-chain fatty acid levels in plasma were analyzed using gas chromatography (GC-FID). Statistical analysis was performed using SPSS 20.0 software; ≤ 0.05 was considered statistically significant. The fatty acid analysis revealed a significant decrease in the levels of caprylic acid (C:8) and lauric acid (C:12) and a significant increase in the level of capric acid (C:10) in the breast cancer subjects when compared to the control group. The level of caproic acid (C:6) was not significantly increased in the breast cancer subjects. In particular, the HER2- and ER-positive breast cancer subjects showed a decrease in their caprylic acid and lauric acid levels compared to other receptors. The results of the current study imply that lower levels of caprylic and lauric acid may be associated with a higher risk of breast cancer. The relevance of medium-chain fatty acids for preventive and therapeutic interventions will be amplified by further research on the possibility that alteration in a patient's medium-chain fatty acid composition may mechanistically contribute to disease progression or breast cancer risk.
Topics: Humans; Female; Caprylates; Breast Neoplasms; Fatty Acids; Lauric Acids
PubMed: 36558514
DOI: 10.3390/nu14245351 -
Stem Cells and Development Jun 2022Lowest observable adverse effects level (LOAEL) is a standard point-of-departure dose in toxicology. However, first observable adverse effects level (FOAEL) was recently...
Using Live Imaging and Fluorescence Ubiquitinated Cell Cycle Indicator Embryonic Stem Cells to Distinguish G1 Cell Cycle Delays for General Stressors like Perfluoro-Octanoic Acid and Hyperosmotic Sorbitol or G2 Cell Cycle Delay for Mutagenic Stressors like Benzo(a)pyrene.
Lowest observable adverse effects level (LOAEL) is a standard point-of-departure dose in toxicology. However, first observable adverse effects level (FOAEL) was recently reported and is used, in this study, as one criterion to detect a mutagenic stimulus in a live imager. Fluorescence ubiquitinated cell cycle indicator (FUCCI) embryonic stem cells (ESC) are green in the S-G2-M phase of the cell cycle and not green in G1-phase. Standard media change here is a mild stress that delays G1-phase and media change increases green 2.5- to 5-fold. Since stress is mild, media change rapidly increases green cell number, but higher stresses of environmental toxicants and positive control hyperosmotic stress suppress increased green after media change. Perfluoro-octanoic acid (PFOA) and diethyl phthalate (DEP) previously suppressed progression of nongreen to green cell cycle progression. Here, bisphenol A (BPA), cortisol, and positive control hyperosmotic sorbitol also suppress green fluorescence, but benzo(a)pyrene (BaP) at high doses (10 μM) increases green fluorescence throughout the 74-h exposure. Since any stress can affect many cell cycle phases, messenger RNA (mRNA) markers are best interpreted in ratios as dose-dependent mutagens increase in G2/G1 and nonmutagens increase G1/G2. After 74-h exposure, RNAseq detects G1 and G2 markers and increasing BaP doses increase G2/G1 ratios but increasing hyperosmotic sorbitol and PFOA doses increase G1/G2 marker ratios. BaP causes rapid green increase in FOAEL at 2 h of stimulus, whereas retinoic acid caused significant green fluorescence increases only late in culture. Using a live imager to establish FOAEL and G2 delay with FUCCI ESC is a new method to allow commercial and basic developmental biologists to detect drugs and environmental stimuli that are mutagenic. Furthermore, it can be used to test compounds that prevent mutations. In longitudinal studies, uniquely provided by this viable reporter and live imager protocol, follow-up can be done to test whether the preventative compound itself causes harm.
Topics: Benzo(a)pyrene; Caprylates; Cell Cycle; Cell Division; Embryonic Stem Cells; Fluorescence; Mutagens; Sorbitol
PubMed: 35678645
DOI: 10.1089/scd.2021.0330 -
The Journal of Physical Chemistry... Apr 2021Perfluorinated acids (PFAs) are widely used synthetic chemical compounds, highly resistant to environmental degradation. The widespread PFA contamination in remote...
Perfluorinated acids (PFAs) are widely used synthetic chemical compounds, highly resistant to environmental degradation. The widespread PFA contamination in remote regions such as the High Arctic implies currently not understood long-range atmospheric transport pathways. Here, we report that perfluorooctanoic acid (PFOA) initiates heterogeneous ice nucleation at temperatures as high as -16 °C. In contrast, the eight-carbon octanoic acid, perfluorooctanesulfonic acid, and deprotonated PFOA showed poor ice nucleating capabilities. The ice nucleation ability of PFOA correlates with the formation of a PFOA monolayer at the air-water interface, suggesting a mechanism in which the aligned hydroxyl groups of the carboxylic acid moieties provide a lattice matching to ice. The ice nucleation capabilities of fluorinated compounds like PFOA might be relevant for cloud glaciation in the atmosphere and the removal of these persistent pollutants by wet deposition.
PubMed: 33789043
DOI: 10.1021/acs.jpclett.1c00604 -
International Journal of Molecular... May 2022The food flavour additive octanoic acid (C8:0) is also a metabolite of the entomopathogenic fungus , which efficiently infects and rapidly kills . GC-MS analysis...
The food flavour additive octanoic acid (C8:0) is also a metabolite of the entomopathogenic fungus , which efficiently infects and rapidly kills . GC-MS analysis confirmed the presence of C8:0 in insecticidal fraction FR3 extracted from filtrate. Topical administration of C8:0 had a dose-dependent effect on survival rates of larvae but not on pupation or adult eclosion times of the survivors. Topically applied C8:0 was more toxic to adults than larvae (LD100 for adults 18.33 ± 2.49 vs. 33.56 ± 2.57 µg/mg of body mass for larvae). The administration of C8:0 on the cuticle of larvae and adults, in amounts corresponding to their LD50 and LD100 doses, had a considerable impact on the two main defense systems engaged in protecting against pathogens, causing serious changes in the developmental-stage-specific profiles of free fatty acids (FFAs) covering the cuticle of larvae and adults and damaging larval hemocytes. In vitro cultures of hemocytes, either directly treated with C8:0 or taken from C8:0 treated larvae, revealed deformation of hemocytes, disordered networking, late apoptosis, and necrosis, as well as caspase 1-9 activation and elevation of 8-OHdG level. C8:0 was also confirmed to have a cytotoxic effect on the SF-9 insect cell line, as determined by WST-1 and LDH tests.
Topics: Animals; Antifungal Agents; Caprylates; Conidiobolus; Hemocytes; Insecticides; Larva; Lepidoptera; Moths
PubMed: 35563592
DOI: 10.3390/ijms23095204 -
Angewandte Chemie (International Ed. in... Oct 2022The production of L-lactide from L-lactic acid involves a substantial formation of meso-lactide as an impurity, and, upon polymerization with the industrial catalyst tin...
The production of L-lactide from L-lactic acid involves a substantial formation of meso-lactide as an impurity, and, upon polymerization with the industrial catalyst tin octanoate, results in poly(L-lactic acid) of reduced crystallinity due to stereoerrors randomly distributed along the polymer chains. We describe a new approach wherein, instead of avoiding stereoerrors by removing the meso-lactide prior to polymerization, the stereoerrors in the polymer are tolerated, by crowding them in a stereogradient copolymer. A zirconium complex of an amine tris(phenolate) ligand is found to exhibit very high syndioselectivity in the ring opening polymerization catalysis of meso-lactide at room temperature, and gives rise to stereogradient copolymers in the polymerization of mixtures of meso-lactide/L-lactide in the melt at 180 °C. Relative to the stereo-random copolymers obtained with tin octanoate, the stereogradient copolymers exhibit enhanced crystallinities manifested in lower solubilities and higher melting temperatures and enthalpies.
Topics: Amines; Caprylates; Dioxanes; Lactic Acid; Ligands; Polyesters; Polymers; Tin; Zirconium
PubMed: 35789524
DOI: 10.1002/anie.202207652 -
The Laryngoscope Aug 2019The purpose of this study was to determine the effects of octanoic acid on acoustic, perceptual, and functional aspects of essential voice tremor (EVT). (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES/HYPOTHESIS
The purpose of this study was to determine the effects of octanoic acid on acoustic, perceptual, and functional aspects of essential voice tremor (EVT).
STUDY DESIGN
Prospective, double-blind, placebo-controlled, crossover study.
METHODS
Sixteen participants with a diagnosis of EVT were randomized to a 3-week dosing condition of octanoic acid or placebo, followed by a 2-week washout period and crossover to the other condition for an additional 3 weeks. Baseline and post-testing sessions were completed before and at the completion of each condition. Primary outcome measures were the magnitude of amplitude and frequency tremor, measured from the acoustic signal. Secondary outcomes were auditory-perceptual ratings of tremor severity and self-ratings of voice handicap.
RESULTS
Magnitude of amplitude and frequency tremor were significantly lower after 3 weeks of octanoic acid dosing as compared to the placebo condition. Auditory-perceptual ratings of tremor severity did not show significant differences between conditions. A trend toward better voice was seen for the sustained vowel ratings, but not the sentence-level ratings. No significant differences between conditions were seen on self-reported voice disability as assessed on the Voice Handicap Index-10.
CONCLUSIONS
The results of this controlled investigation support the potential utility of octanoic acid for reducing the magnitude of tremor in people with EVT. Further research is needed to determine whether different dosing or treatment combinations can improve functional communication in EVT.
LEVEL OF EVIDENCE
1 Laryngoscope, 129:1882-1890, 2019.
Topics: Aged; Caprylates; Cross-Over Studies; Double-Blind Method; Essential Tremor; Female; Humans; Male; Middle Aged; Prospective Studies; Severity of Illness Index; Treatment Outcome; Voice; Voice Disorders
PubMed: 30585335
DOI: 10.1002/lary.27695 -
Brain Sciences Oct 2017This review focuses on biomarkers associated with the outcome of traumatic brain injury (TBI) patients, such as caspase-3; total antioxidant capacity; melatonin; S100B... (Review)
Review
This review focuses on biomarkers associated with the outcome of traumatic brain injury (TBI) patients, such as caspase-3; total antioxidant capacity; melatonin; S100B protein; glial fibrillary acidic protein (GFAP); glutamate; lactate; brain-derived neurotrophic factor (BDNF); substance P; neuron-specific enolase (NSE); ubiquitin carboxy-terminal hydrolase L-1 (UCH-L1); tau; decanoic acid; and octanoic acid.
PubMed: 29076989
DOI: 10.3390/brainsci7110142