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Prostaglandins, Leukotrienes, and... Aug 2020High grade glial tumors (HGGs) including anaplastic astrocytoma (WHO Grade-III) and glioblastoma multiforme (GBM, WHO Grade-IV) are among the most malignant cancers... (Review)
Review
High grade glial tumors (HGGs) including anaplastic astrocytoma (WHO Grade-III) and glioblastoma multiforme (GBM, WHO Grade-IV) are among the most malignant cancers known to man. Due to their defective mitochondria, HGG cells consume glucose via glycolysis even in the presence of oxygen. Overall survival is worse in HGG patients that are hyperglycemic. Unlike normal neural cells, HGG cells cannot efficiently metabolize ketone bodies for energy. Thus, a metabolic treatment based on therapeutic ketosis (reduced glucose with elevated ketone bodies) was proposed to treat GBM and was supoported from preclinical studies. Caprylic (octanoic) acid, a monocarboxylated saturated fatty acid, is among the best producers of ketone bodies and induces necrosis of experimental tumors at high dose. Caprylic acid is enriched in coconut and in goat's milk. It is also a posttranslational modifier of the ghrelin hormone and is produced in trace amounts in human tissues. Caprylic acid is a straight-chain isomer of the antiepileptic valproic acid, which is used in treatment of HGG-associated seizures and which may increase survival in GBM patients according to epidemiological observations. Among the valproic acids analogs tested, caprylic acid is the most potent molecule to block C6 astrocytoma cell growth in vitro and accumulates selectively within glial cells as shown by Positron Emission Tomography in vivo. Caprylic acid blocks glycolysis both in healthy liver and in malignant liver cells, which is more prominent in the latter and also lowers blood glucose. Noteworthy, caprylic acid exerts neuroprotective- and mitochondria-protective effects in several models of neurodegenerative diseases. Boost injections of caprylic acid at non-toxic levels during classical ketogenic metabolic therapy may fortify antitumor actions and reduce systemic toxicity by differential programming of mitochondrial and other metabolic pathways.
Topics: Animals; Antineoplastic Agents; Brain Neoplasms; Caprylates; Glioblastoma; Humans
PubMed: 32512365
DOI: 10.1016/j.plefa.2020.102142 -
Lipids Jul 2022Gastric emptying (GE) is the process of food being processed by the stomach and delivered to the small intestine where nutrients such as lipids are absorbed into the... (Review)
Review
Gastric emptying (GE) is the process of food being processed by the stomach and delivered to the small intestine where nutrients such as lipids are absorbed into the blood circulation. The combination of an easy and inexpensive method to measure GE such as the CO breath test using the stable isotope [ C]octanoic acid with semi-mechanistic modeling could foster a wider application in nutritional studies to further understand the metabolic response to food. Here, we discuss the use of the [ C]octanoic acid breath test to label the solid phase of a meal, and the factors that influence GE to support mechanistic studies. Furthermore, we give an overview of existing mathematical models for the interpretation of the breath test data and how much nutritional studies could benefit from a physiological based pharmacokinetic model approach.
Topics: Breath Tests; Caprylates; Carbon Isotopes; Gastric Emptying
PubMed: 35799422
DOI: 10.1002/lipd.12352 -
Food and Chemical Toxicology : An... Apr 2020
Review
Topics: Animals; Caprylates; Humans; Perfume; Registries; Risk Assessment; Toxicity Tests; Volatile Organic Compounds
PubMed: 32199972
DOI: 10.1016/j.fct.2020.111271 -
European Review For Medical and... 2013Digestion is a complex process regulated by several factors. Among these, one of the most important is the time of gastric emptying. A delayed gastric emptying time can... (Review)
Review
Digestion is a complex process regulated by several factors. Among these, one of the most important is the time of gastric emptying. A delayed gastric emptying time can be caused by several factors and can generate considerable discomfort in humans. It ranges from mild to real debilitating disorders. Until now, different tests are suggested to study the gastric emptying time. The present review presents the mayor cause and the main symptoms linked to delayed gastric emptying and will focus on the (13)C-octanoid acid breath test, as a good candidate for studying solid gastric emptying time.
Topics: Biomarkers; Breath Tests; Caprylates; Carbon Dioxide; Carbon Isotopes; Gases; Gastric Emptying; Gastroparesis; Humans; Predictive Value of Tests; Time Factors
PubMed: 24443070
DOI: No ID Found -
JPEN. Journal of Parenteral and Enteral... Aug 2022Acute liver injury (ALI) is an essential component of sepsis associated with poor outcomes. Octanoic acid (OA), a medium-chain fatty acid, has a protective effect on...
BACKGROUND
Acute liver injury (ALI) is an essential component of sepsis associated with poor outcomes. Octanoic acid (OA), a medium-chain fatty acid, has a protective effect on sepsis-induced organ damage, and autophagy is an adaptive response to sepsis. However, the underlying mechanism by which OA prevents ALI remains unknown. Therefore, we investigated whether OA-rich enteral nutrition (EN) prevented lipopolysaccharide (LPS)-induced ALI through the c-Jun N-terminal kinase (JNK)-dependent autophagy.
METHODS
Firstly, Sprague Dawley rats were randomly divided into four groups (sham, LPS, LPS + EN, and LPS + EN + OA) to detect the effect of OA-rich EN on LPS-induced ALI. Then, rats were randomly divided into five groups (sham, LPS, LPS + EN + OA, LPS + EN + OA + anisomycin (AN), and LPS + SP600125) to explore the mechanism by which OA-rich EN prevented ALI. EN and OA-rich EN were conducted through gastric tubes for 3 days. The liver protective effects were measured by liver histopathological changes, enzymes, inflammatory cytokines of serum and liver, the levels of autophagy, and JNK activity.
RESULTS
OA-rich EN inhibited JNK activity, up-regulated autophagy and prevented LPS-induced ALI. Inhibition of JNK activity conferred by SP promoted autophagy and prevented LPS-induced ALI. Moreover, the protective effect of autophagy and inhibition of JNK activity conferred by OA-rich EN on ALI was counteracted by AN.
CONCLUSION
OA-rich EN prevented LPS-induced ALI through JNK-dependent autophagy. This result suggested that OA-rich EN may be a therapeutic potential for ALI in patients with sepsis.
Topics: Acute Lung Injury; Animals; Autophagy; Caprylates; Enteral Nutrition; JNK Mitogen-Activated Protein Kinases; Lipopolysaccharides; Liver; Rats; Rats, Sprague-Dawley; Sepsis
PubMed: 34719794
DOI: 10.1002/jpen.2297 -
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 -
FEMS Yeast Research Mar 2021The medium-chain fatty acid octanoic acid is an important platform compound widely used in industry. The microbial production from sugars in Saccharomyces cerevisiae is...
The medium-chain fatty acid octanoic acid is an important platform compound widely used in industry. The microbial production from sugars in Saccharomyces cerevisiae is a promising alternative to current non-sustainable production methods, however, titers need to be further increased. To achieve this, it is essential to have in-depth knowledge about the cell physiology during octanoic acid production. To this end, we collected the first RNA-Seq data of an octanoic acid producer strain at three time points during fermentation. The strain produced higher levels of octanoic acid and increased levels of fatty acids of other chain lengths (C6-C18) but showed decreased growth compared to the reference. Furthermore, we show that the here analyzed transcriptomic response to internally produced octanoic acid is notably distinct from a wild type's response to externally supplied octanoic acid as reported in previous publications. By comparing the transcriptomic response of different sampling times, we identified several genes that we subsequently overexpressed and knocked out, respectively. Hereby we identified RPL40B, to date unknown to play a role in fatty acid biosynthesis or medium-chain fatty acid tolerance. Overexpression of RPL40B led to an increase in octanoic acid titers by 40%.
Topics: Biosynthetic Pathways; Caprylates; Fermentation; Gene Expression Profiling; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins
PubMed: 33599754
DOI: 10.1093/femsyr/foab011 -
Molecular Metabolism Apr 2020Nutrient sensing by hypothalamic neurons is critical for the regulation of food intake and energy expenditure. We aimed to identify long- and medium-chain fatty acid...
OBJECTIVES
Nutrient sensing by hypothalamic neurons is critical for the regulation of food intake and energy expenditure. We aimed to identify long- and medium-chain fatty acid species transported into the brain, their effects on energy balance, and the mechanisms by which they regulate activity of hypothalamic neurons.
METHODS
Simultaneous blood and cerebrospinal fluid (CSF) sampling was undertaken in rats and metabolic analyses using radiolabeled fatty acid tracers were performed on mice. Electrophysiological recording techniques were used to investigate signaling mechanisms underlying fatty acid-induced changes in activity of pro-opiomelanocortin (POMC) neurons.
RESULTS
Medium-chain fatty acid (MCFA) octanoic acid (C8:0), unlike long-chain fatty acids, was rapidly transported into the hypothalamus of mice and almost exclusively oxidized, causing rapid, transient reductions in food intake and increased energy expenditure. Octanoic acid differentially regulates the excitability of POMC neurons, activating these neurons directly via GPR40 and inducing inhibition via an indirect non-synaptic, purine, and adenosine receptor-dependent mechanism.
CONCLUSIONS
MCFA octanoic acid is a central signaling nutrient that targets POMC neurons via distinct direct and indirect signal transduction pathways to instigate changes in energy status. These results could explain the beneficial health effects that accompany MCFA consumption.
Topics: Animals; Caprylates; Energy Metabolism; Male; Neurons; Rats; Rats, Wistar
PubMed: 32180560
DOI: 10.1016/j.molmet.2020.01.002 -
In Vivo (Athens, Greece) 2023Acute liver injury is the hallmark of organ failure in sepsis. Enteral nutrition (EN) is an important clinical therapeutic measure in septic patients. However, the...
BACKGROUND/AIM
Acute liver injury is the hallmark of organ failure in sepsis. Enteral nutrition (EN) is an important clinical therapeutic measure in septic patients. However, the therapeutic effect of EN alone is not obvious. Here, we investigated whether octanoic acid (OA)-rich EN alleviated acute liver injury through PPARγ/STAT-1/MyD88 pathway in endotoxemic rats.
MATERIALS AND METHODS
First, rats were randomly divided into four groups: Sham, Lipopolysaccharide (LPS), LPS+EN and LPS+EN+OA groups to investigate the effect of OA-rich EN on LPS-induced acute liver injury in endotoxemic rats. Then rats were randomly divided into five groups: Sham, LPS, LPS+EN+OA, LPS+EN+OA+SR202 (SR) and LPS+ pioglitazone (PI) groups to examine whether OA-rich EN alleviated acute liver injury through the PPARγ/STAT-1/MyD88 pathway. Rats received nutrition support via a gastric tube for 3 days. We evaluated the liver histology, apoptosis, liver enzymes and inflammatory cytokine levels in the liver and serum. PPARγ/STAT-1/MyD88 pathway was also measured.
RESULTS
OA-rich EN inhibited the phosphorylation of STAT-1 and the activity of MyD88 by activating PPARγ and alleviating LPS-induced acute liver injury more effectively than EN alone in endotoxemic rats. The use of SR counteracted the effect of OA-rich EN on acute liver injury. Meanwhile, PI showed effects similar to OA-rich EN in endotoxemic rats.
CONCLUSION
OA-rich EN alleviated acute liver injury through PPARγ/STAT-1/MyD88 pathway in endotoxemic rats.
Topics: Rats; Animals; Enteral Nutrition; Lipopolysaccharides; Myeloid Differentiation Factor 88; PPAR gamma; Liver
PubMed: 37369501
DOI: 10.21873/invivo.13246 -
European Review For Medical and... 2005Non invasive evaluation of gastric emptying is generally performed by scintigraphy which is, however, difficult to perform and not suitable to children and childbearing... (Review)
Review
Non invasive evaluation of gastric emptying is generally performed by scintigraphy which is, however, difficult to perform and not suitable to children and childbearing women. A new method based on stable isotope breath testing analysis has been introduced in clinical practice: the 13C-octanoic acid breath test. In this paper, an overview of the current knowledge on this technique is given with special emphasis on the principle of the test, the mathematics used to analyse the results, and the physiological, pathological, and pharmacological aspects of gastric emptying studied with this new method.
Topics: Breath Tests; Caprylates; Carbon Isotopes; Gastric Emptying; Humans; Models, Theoretical; Stomach Diseases
PubMed: 16457123
DOI: No ID Found