Medium-chain Fatty Acids Research Articles

Parenteral nutrition at home/long-term parenteral nutrition.

Some diseases require that patients receive parenteral nutrition (PN) over a prolonged time period. Long-term administration of PN can further complicate an already complex therapy, posing additional risk of potential complications. This article is based on presentations and discussions held at the International Safety and Quality of PN Summit, providing insights into aspects of home PN (HPN) and examples of good HPN practice. One critical step in the HPN process is when patients transition from a hospital to a home setting, and vice versa. Generally, electronic PN ordering is not feasible in an HPN setting, leading to potential difficulties in communication and coordination. HPN requires that patients (or their home caregivers) administer PN, and thus their education and competency are crucial. Likewise, the choice of PN formulation is of great importance. For example, using more modern intravenous lipid emulsions containing medium-chain triglycerides, olive oil, and/or fish oil can provide benefits in terms of liver function during long-term HPN. Internationally, there are wide variations in delivery of HPN, with compounded PN dominating in some countries while others make greater use of market-authorized multichamber bags (MCBs). Patient-related factors, institutional considerations, and the availability of different MCB formulations, are also contributing factors guiding formulation and delivery system preferences. Education and communication remain key components of a successful HPN process. The information shared here may help to motivate efforts to improve HPN processes and to consider the often-differing perspectives of patients and their healthcare professionals.

10-hydroxy decanoic acid, trans-10-hydroxy-2-decanoic acid, and sebacic acid: Source, metabolism, and potential health functionalities and nutraceutical applications.

The popularity of royal jelly (RJ) as a functional food has attracted attention from various industries, especially nutraceuticals, due to the increasing demand from health enthusiasts. Sebacic acid, 10-hydroxy decanoic acid, and trans-10-hydroxy-2-decanoic acid are the primary medium-chain fatty acids (MCFAs) within RJ responsible for their health benefits. This review aims to consolidate information on these MCFAs' metabolic relationship and health functionalities in nutraceutical applications. We also investigated the natural characteristics mediated by these MCFAs and their metabolism in organisms. Finally, the production of these MCFAs using conventional (from castor oil) and alternative (from RJ) pathways was also discussed. This review can be a reference for using them as functional ingredients in nutraceutical industries.

Feedback of chain elongation microorganisms on iron-based conductive materials: Enhanced microbial functions and biotoxicity adaptation mechanisms

Despite the increased research efforts aimed at understanding iron-based conductive materials (CMs) for facilitating chain elongation (CE) to produce medium chain fatty acids (MCFAs), the impact of these materials on microbial community functions and the adaptation mechanisms to their biotoxicity remain unclear. This study found that the supply of zero-valent iron (ZVI) and magnetite enhanced the MCFAs carbon-flow distribution by 26 % and 52 %, respectively. Metagenomic analysis revealed the upregulation of fatty acid metabolism, pyruvate metabolism and ABC transporters with ZVI and magnetite. The predominant functional microorganisms were Massilibacterium and Tidjanibacter with ZVI, and were Petrimonas and Candidatus_Microthrix with magnetite. Furthermore, it was demonstrated that CE microorganisms respond and adapt to the biotoxicity of iron-based CMs by adjusting Two-component system and Quorum sensing for the first time. In summary, this study provided a new deep-insight on the feedback mechanisms of CE microorganisms on iron-based CMs.

Critical Role of Mitochondrial Fatty Acid Metabolism in Normal Cell Function and Pathological Conditions.

There is a "popular" belief that a fat-free diet is beneficial, supported by the scientific dogma indicating that high levels of fatty acids promote many pathological metabolic, cardiovascular, and neurodegenerative conditions. This dogma pressured scientists not to recognize the essential role of fatty acids in cellular metabolism and focus on the detrimental effects of fatty acids. In this work, we critically review several decades of studies and recent publications supporting the critical role of mitochondrial fatty acid metabolism in cellular homeostasis and many pathological conditions. Fatty acids are the primary fuel source and essential cell membrane building blocks from the origin of life. The essential cell membranes phospholipids were evolutionarily preserved from the earlier bacteria in human subjects. In the past century, the discovery of fatty acid metabolism was superseded by the epidemic growth of metabolic conditions and cardiovascular diseases. The association of fatty acids and pathological conditions is not due to their "harmful" effects but rather the result of impaired fatty acid metabolism and abnormal lifestyle. Mitochondrial dysfunction is linked to impaired metabolism and drives multiple pathological conditions. Despite metabolic flexibility, the loss of mitochondrial fatty acid oxidation cannot be fully compensated for by other sources of mitochondrial substrates, such as carbohydrates and amino acids, resulting in a pathogenic accumulation of long-chain fatty acids and a deficiency of medium-chain fatty acids. Despite popular belief, mitochondrial fatty acid oxidation is essential not only for energy-demanding organs such as the heart, skeletal muscle, and kidneys but also for metabolically "inactive" organs such as endothelial and epithelial cells. Recent studies indicate that the accumulation of long-chain fatty acids in specific organs and tissues support the impaired fatty acid oxidation in cell- and tissue-specific fashion. This work, therefore, provides a basis to challenge these established dogmas and articulate the need for a paradigm shift from the "pathogenic" role of fatty acids to the critical role of fatty acid oxidation. This is important to define the causative role of impaired mitochondrial fatty acid oxidation in specific pathological conditions and develop novel therapeutic approaches targeting mitochondrial fatty acid metabolism.

Octanoic acid mitigates busulfan-induced blood-testis barrier damage by alleviating oxidative stress and autophagy

BackgroundThe management of male infertility continues to encounter an array of challenges and constraints, necessitating an in-depth exploration of novel therapeutic targets to enhance its efficacy. As an eight-carbon medium-chain fatty acid, octanoic acid (OCA) shows promise for improving health, yet its impact on spermatogenesis remains inadequately researched.MethodsMass spectrometry was performed to determine the fatty acid content and screen for a pivotal lipid component in the serum of patients with severe spermatogenesis disorders. The sperm quality was examined, and histopathological analysis and biotin tracer tests were performed to assess spermatogenesis function and the integrity of the blood-testis barrier (BTB) in vivo. Cell-based in vitro experiments were carried out to investigate the effects of OCA administration on Sertoli cell dysfunction. This research aimed to elucidate the mechanism by which OCA may influence the function of Sertoli cells.ResultsA pronounced reduction in OCA content was observed in the serum of patients with severe spermatogenesis disorders, indicating that OCA deficiency is related to spermatogenic disorders. The protective effect of OCA on reproduction was tested in a mouse model of spermatogenic disorder induced by busulfan at a dose 30 mg/kg body weight (BW). The mice in the study were separated into distinct groups and administered varying amounts of OCA, specifically at doses of 32, 64, 128, and 256 mg/kg BW. After evaluating sperm parameters, the most effective dose was determined to be 32 mg/kg BW. In vivo experiments showed that treatment with OCA significantly improved sperm quality, testicular histopathology and BTB integrity, which were damaged by busulfan. Moreover, OCA intervention reduced busulfan-induced oxidative stress and autophagy in mouse testes. In vitro, OCA pretreatment (100 µM) significantly ameliorated Sertoli cell dysfunction by alleviating busulfan (800 µM)-induced oxidative stress and autophagy. Moreover, rapamycin (5 µM)-induced autophagy led to Sertoli cell barrier dysfunction, while OCA administration exerted a protective effect by alleviating autophagy.ConclusionsThis study demonstrated that OCA administration suppressed oxidative stress and autophagy to alleviate busulfan-induced BTB damage. These findings provide a deeper understanding of the toxicology of busulfan and a promising avenue for the development of novel OCA-based therapies for male infertility.

Effect of different inoculation strategies of mixed culture Saccharomyces cerevisiae/Oenococcus oeni on the aroma quality of Chardonnay wine

There has been growing interest in the use of mixed cultures comprised of Oenococcus oeni and Saccharomyces cerevisiae to produce wine with local style and typicality. This study has investigated the influence of the inoculation protocol of O. oeni on the fermentation kinetics and aromatic profile of Chardonnay wine. The one selected autochthonous O. oeni strain (ZX-1) inoculated at different stages of the alcoholic fermentation process successfully completed malolactic fermentation (MLF). Co-inoculum of S. cerevisiae and O. oeni enabled simultaneous alcoholic fermentation and MLF, leading to at least a 30 % reduction in the total fermentation time when compared to the sequential inoculation process, which was attributed to the lower ethanol stress. Meanwhile, co-inoculum stimulated the accumulation of volatile aroma compounds in Chardonnay wine. In particular, the mixed modality where the O. oeni strain ZX-1 was inoculated 48 h after S. cerevisiae allowed higher levels of terpenes, acetates, short-chain, and medium-chain fatty acid ethyl esters to be produced, which may result in the enhanced floral and fruity attributes of wine. Aroma reconstitution and omission models analysis revealed that the accumulation of linalool, geraniol, isoamyl acetate, ethyl hexanoate, and ethyl caprylate during the mixed fermentation process enhanced the stone fruit, tropical fruit, and citrus aromas in Chardonnay wine. Therefore, the simultaneous fermentation of S. cerevisiae and autochthonous O. oeni ZX-1 has a positive effect on MLF and contributes to producing wines with distinctive style.

Obese mice have decreased uterine contractility and altered energy metabolism in the uterus at term gestation†.

Over 35% of reproductive-age women in the USA have obesity, putting them at increased risk for numerous obstetric complications due to abnormal labor. While the association between maternal obesity and abnormal labor has been well documented, the mechanisms responsible for this remain understudied. The uterine smooth muscle, myometrium, has high energy needs in order to fuel regular uterine contractions during parturition. However, the precise mechanisms by which the myometrium meets its energy demands has not been defined. Here, our objective was to define the effects of obesity on energy utilization in the myometrium during labor. We generated a mouse model of maternal diet-induced obesity and found that these mice had a higher rate of dystocia than control chow-fed mice. Moreover, compared to control chow-fed mice, DIO mice at term, both before and during labor had lower in vivo spontaneous uterine contractility. Untargeted transcriptomic and metabolomic analyses suggest that diet-induced obesity is associated with elevated long-chain fatty acid uptake and utilization in the uterus, but also an accumulation of medium-chain fatty acids. Diet-induced obesity uteri also had an increase in the abundance of long chain-specific beta-oxidation enzymes, which may be responsible for the observed increase in long-chain fatty acid utilization. This altered energy substrate utilization may be a contributor to the observed contractile dysfunction.

Continuous chain elongation process for carbon resource recovery from excess sludge: Enhanced n-caprylate production and specific microbial functionalities

Thermal hydrolyzed sludge (THS) exhibits considerable promise in generating medium-chain fatty acids (MCFAs) through chain elongation (CE) technology. This study developed a novel continuous CE process using THS as the substrate, achieving an optimal ethanol loading rate (5.8 g COD/L/d) and stable MCFA production at 10.9 g COD/L, with a rate of 3.6 g COD/L/d. The MCFAs primarily comprised n-caproate and n-caprylate, representing 41.5 % and 54.3 % of the total MCFAs, respectively. Utilization efficiencies for ethanol and acetate were nearly complete at 100 % and 92.8 %, respectively. Key microbial taxa identified under these optimal conditions included Alcaligenes, SRB2, Sporanaerobacter, and Kurthia, which were instrumental in critical pathways such as the generation of acetyl-CoA, the initial carboxylation of acetyl-CoA, the fatty acid biosynthesis cycle, and energy metabolism. This research provides a theoretical and technical blueprint for converting waste sludge into valuable MCFAs, promoting sustainable waste-to-resource strategies.

The artificial intelligence and design of experiment assisted in the development of progesterone-loaded solid-lipid nanoparticles for transdermal drug delivery

The application of Artificial Intelligence (AI) has the potential to revolutionize the formulation development of nanomedicine. This study investigated the physicochemical characteristics of progesterone-loaded solid-lipid nanoparticles (PG-SLNs) produced through an emulsification–ultrasonication process, with a focus on demonstrating the efficacy of this controlled preparation method via the Design of Experiments (DoE) and Artificial Neural Networks (ANN). Critical quality factors, including stearic acid, medium chain triglycerides (MCT), Pluronic F-127, and the amount of propylene glycol (PG), were explored using DoE to streamline experimental setups. The concentration of stearic acid was identified as a crucial factor influencing PG-SLN physicochemical properties, impacting particle size (PS), polydispersity index (PDI), zeta potential (ZP), and %drug loading (%DL). Optimal conditions for PS, PDI, ZP, and %DL were identified. DoE revealed acceptable values across multiple runs, and the ANN model demonstrates high prediction accuracy, surpassing Response Surface Methodology (RSM). The selected PG-SLN formulation was tested for transdermal drug delivery, showing improved permeation compared to PG suspension. Loading with limonene further enhances transdermal drug delivery, attributed to limonene’s role as a penetration enhancer. Moreover, the selected PG-SLN formulation was found to be safe and non-toxic to neuronal cells. The combination of DoE and ANN was proposed to enhance predictive ability. This research highlights the potential of PG-SLNs in transdermal drug delivery, emphasizing the role of limonene as a safe and effective enhancer. The study contributes to the growing interest in applying AI tools in pharmaceutical and biomedical fields for improved predictive modeling.

Structural basis for expanded substrate specificities of human long chain acyl-CoA dehydrogenase and related acyl-CoA dehydrogenases

Crystal structures of human long-chain acyl-CoA dehydrogenase (LCAD) and the catalytically inactive Glu291Gln mutant, have been determined. These structures suggest that LCAD harbors functions beyond its historically defined role in mitochondrial β-oxidation of long and medium-chain fatty acids. LCAD is a homotetramer containing one FAD per 43 kDa subunit with Glu291 as the catalytic base. The substrate binding cavity of LCAD reveals key differences which makes it specific for longer and branched chain substrates. The presence of Pro132 near the start of the E helix leads to helix unwinding that, together with adjacent smaller residues, permits binding of bulky substrates such as 3α, 7α, l2α-trihydroxy-5β-cholestan-26-oyl-CoA. This structural element is also utilized by ACAD11, a eucaryotic ACAD of unknown function, as well as bacterial ACADs known to metabolize sterol substrates. Sequence comparison suggests that ACAD10, another ACAD of unknown function, may also share this substrate specificity. These results suggest that LCAD, ACAD10, ACAD11 constitute a distinct class of eucaryotic acyl CoA dehydrogenases.

In Vitro Predictive Model for Intestinal Lymphatic Uptake: Exploration of Additional Enhancers and Inhibitors.

Drug absorption via chylomicrons holds significant implications for both pharmacokinetics and pharmacodynamics. However, a mechanistic understanding of predicting in vivo intestinal lymphatic uptake remains largely unexplored. This study aimed to delve into the intestinal lymphatic uptake of drugs, investigating both enhancement and inhibition using various excipients through our previously established in vitro model. It also examined the applicability of the model by assessing the lymphatic uptake enhancement of a lymphotropic formulation with linoleoyl polyoxyl-6 glycerides using the same model. The model successfully differentiated among olive, sesame, and peanut oils in terms of lymphatic uptake. However, it did not distinguish between oils containing long-chain fatty acids and coconut oil. Coconut oil, known for its abundance of medium-chain fatty acids, outperformed other oils. This heightened uptake was attributed to the superior emulsification of this oil in artificial chylomicron media due to its high content of medium-chain fatty acids. Additionally, the enhanced uptake of the tested formulation with linoleoyl polyoxyl-6 glycerides underscored the practical applicability of this model in formulation optimization. Moreover, data suggested that increasing the zeta potential of Intralipid® using sodium lauryl sulfate (SLS) and decreasing it using (+/-) chloroquine led to enhanced and reduced uptake in the in vitro model, respectively. These findings indicate the potential influence of the zeta potential on intestinal lymphatic uptake in this model, though further research is needed to explore the possible translation of this mechanism in vivo.

Sourdough bread enriched with exopolysaccharides and gazpacho by-products modulates in vitro the microbiota dysbiosis

Sourdough bread enriched with soluble fiber (by in-situ exopolysaccharides production) and insoluble fiber (by gazpacho by-products addition) showed prebiotic effects an in vitro dynamic colonic fermentation performance with obese volunteer's microbiota. Bifidobacterium population was maintained whereas Lactobacillus increased throughout the colonic sections. Conversely, Enterobacteriaceae and Clostridium groups clearly decreased.Specific bacteria associated with beneficial effects increased in the ascending colon (Lactobacillus fermentum, Lactobacillus paracasei, Bifidobacterium longum and Bifidobacterium adolescentis) whereas Eubacterium eligens, Alistipes senegalensis, Prevotella copri and Eubacterium desmolans increased in the transversal and descending colon. Additionally, Blautia faecis and Ruminococcus albus increased in the transversal colon, and Bifidobacterium longum, Roseburia faecis and Victivallis vadensis in the descending colon.Bifidobacterium and Lactobacillus fermented the in-situ exopolysaccharides and released pectins from gazpacho by-products, as well as cellulosic degraded bacteria. This increased the short and medium chain fatty acids. Acetic acid, as well as butyric acid, increased throughout the colonic tract, which showed greater increases only in the transversal and descending colonic segments. Conversely, propionic acid was slightly affected by the colonic fermentation.These results show that sourdough bread is a useful food matrix for the enrichment of vegetable by-products (or other fibers) in order to formulate products with microbiota modulatory capacities.

Enhanced medium-chain fatty acid production from sewage sludge by combined electro-fermentation and anaerobic fermentation

Electro-fermentation (EF) was combined with anaerobic fermentation (AF) to promote medium-chain fatty acid (MCFA) from sewage sludge. Results showed that EF at acidification process significantly increased short-chain fatty acid (SCFA) production of by 0.5 times (82.4 mmol C/L). AF facilitated the chain elongation (CE) process by enhancing the SCFA conversion. Combined EF at acidification and AF at CE (EF-AF) achieved the highest MCFA production of 27.9 mmol C/L, which was 20 %-866 % higher than the other groups. Electrochemical analyses showed that enhanced SCFA and MCFA production was accompanied with good electrochemical performance at acidification and CE. Microbial analyses showed that EF-AF promoted MCFA production by enriching electrochemically active bacteria (EAB, Bacillus sp.). Enzyme analyses indicated that EF-AF promoted MCFA production by enriching the functional enzymes involved in Acetyl-CoA formation and the fatty acid biosynthesis (FAB) pathway. This study provided new insights into the production of MCFA from enhanced sewage sludge.

Towards natural care products: Structural and deposition studies of bio-based polymer and surfactant mixtures

Oppositely charged polymer-surfactant systems are expected to interact with formation of coacervate complexes near composition of charge-neutrality. Such behaviour is widely used in formulated products (e.g. household and personal care), where the co-deposition of coacervates and active ingredients on various surfaces is triggered by dilution. A transition towards the use of more sustainable ingredients is currently ongoing as a response to the need of more environmentally conscious choices in production, albeit slowed down by the often more complex and not fully understood bulk and interfacial behaviour of new ingredients. In this work, mixtures of a medium-chain fatty acid (sodium decanoate) and two grades of bio-based cationic modified inulin were studied. The phase behaviour was determined in a wide composition matrix. The formation of coacervate complexes was observed for the mixture with the higher charge density polymer at a surfactant concentration of 1–3 wt%, close to the surfactant critical micellar concentration in pure water. Such behaviour was confirmed by DLS and SAXS data, suggesting surfactant-polymer complexation in a concentrated phase of packed micelles with a micelle-to-micelle distance of ∼4.5 nm. In situ ellipsometry and neutron reflectometry experiments were conducted to study the effect on surface deposition when diluting. The ellipsometry showed an adsorbed mass of ∼1.3–1.9 mg/m2, consistent with the deposition of a coacervate layer, and considerably higher than the neat, adsorbed polymer layer of ∼0.3 mg/m2. In the case of the neutron reflectometry experiments, dilution was performed before contact with the surface (pre-mixing), and no adsorption of coacervates was observed, but rather the adsorption of a polymer layer (0.49–0.85 mg/m2). The different results obtained with the different techniques highlight the kinetic nature of bulk coacervate formation and deposition, and the competition between these two phenomena. Maximal deposition can be achieved if one can control this time window either by tuning the composition of the system or the experimental set-up, to mimic the conditions of a specific application.

Crystalline Hepatopathy Associated With Bietti Crystalline Dystrophy: A Striking Manifestation of Disordered Fatty Acid Metabolism.

Bietti crystalline dystrophy (BCD) is a rare heritable retinal disease characterized by crystal deposition primarily in the retina. It is associated with atrophy of the retinal pigment epithelium (RPE) and is caused by variants in CYP4V2 , which encodes a cytochrome P450 hemethiolate protein superfamily member. CYP4V2 is involved in the selective hydrolysis of saturated medium chain fatty acids, and patients with BCD demonstrate abnormalities in fatty acid metabolism, including abnormal lipid profiles and the accumulation of the pathogenic crystals within the RPE, which leads to the visual pathologies characteristic of BCD. However, the precise identity of the crystals is currently unknown, and BCD has no established extraocular manifestations. Here, we report granulomatous hepatitis associated with abundant diffuse crystalline clefts in the hepatic parenchyma in 3 patients with retinal dystrophy and dyslipidemia: 2 with pathogenic CYP4V2 variants and 1 patient with clinical ophthalmologic findings suggestive of BCD but without available genetic testing. The unique and striking histologic features unifying the liver biopsies in all 3 patients strongly support a process related to abnormal fatty acid metabolism underlying the genetic disease of BCD, expanding the spectrum of BCD and shedding light on the importance of CYP4V2 in systemic fatty acid metabolism.

Novel milk fat fractions for health and functionality obtained by short-path distillation

Medium-chain fatty acids (MCFA) are associated with various health benefits, such as enhanced insulin sensitivity and reduced appetite. The study explored the potential of combining dry or solvent fractionation with short-path distillation (SPD) to obtain milk fat (MF) fractions enriched in MCFA. By using only SPD, a 2-fold increase in MCFA and an 18-fold increase in α-tocopherol in distillates was obtained compared to native MF. The distillate has a lower melting temperature than does MF. Pre-fractionation processes before SPD did not lead to an additional increase in MCFA. The study demonstrates the potential of SPD to produce MF fraction (distillate) with significant enrichment in MCFA, differed thermal behavior, and increased α-tocopherol content while keeping the FA composition and thermal properties of the remaining fraction (retentate) similar to MF as only 10% of the milk fat have been removed.

Characterizations on a GRAS Electrospun Lipid-Polymer Composite Loaded with Tetrahydrocurcumin.

Electrospun/sprayed fiber films and nanoparticles were broadly studied as encapsulation techniques for bioactive compounds. Nevertheless, many of them involved using non-volatile toxic solvents or non-biodegradable polymers that were not suitable for oral consumption, thus rather limiting their application. In this research, a novel electrospun lipid-polymer composite (ELPC) was fabricated with whole generally recognized as safe (GRAS) materials including gelatin, medium chain triglyceride (MCT) and lecithin. A water-insoluble bioactive compound, tetrahydrocurcumin (TC), was encapsulated in the ELPC to enhance its delivery. Confocal laser scanning microscopy (CLSM) was utilized to examine the morphology of this ELPC and found that it was in a status between electrospun fibers and electrosprayed particles. It was able to form self-assembled emulsions (droplets visualized by CLSM) to deliver active compounds. In addition, this gelatin-based ELPC self-assembled emulsion was able to form a special emulsion gel. CLSM observation of this gel displayed that the lipophilic contents of the ELPC were encapsulated within the cluster of the hydrophilic gelatin gel network. The FTIR spectrum of the TC-loaded ELPC did not show the fingerprint pattern of crystalline TC, while it displayed the aliphatic hydrocarbon stretches from MCT and lecithin. The dissolution experiment demonstrated a relatively linear release profile of TC from the ELPC. The lipid digestion assay displayed a rapid digestion of triglycerides in the first 3-6 min, with a high extent of lipolysis. A Caco-2 intestinal monolayer transport study was performed. The ELPC delivered more TC in the upward direction than downwards. MTT study results did not report cytotoxicity for both pure TC and the ELPC-encapsulated TC under 15 μg/mL. Caco-2 cellular uptake was visualized by CLSM and semi-quantified to estimate the accumulation rate of TC in the cells over time.

The addition of Citrus aurantium leaves and tomato pomace in the diet of Awassi ewes and the impact on milk composition and matured cheese

The purpose of this study was to use concentrated feed alternatives with other less expensive feed alternatives in feeding the Awassi ewes and the impact on milk composition and matured cheese. A total of twenty Awassi ewes were used, they were selected in the middle of lactation and divided into two homogeneous groups with weights (47±1.7 kg) and aged 3-4 years, given two different servings of feed (1.5 kg/sheep/day) Milk composition was measured weekly, to make cheese, raw milk control (CON) and Citrus aurantium leaves and tomato pomace (CALTP) is kept separately and chilled. Results indicated that fat and total solid content were high in milk and cheese manufactured in the diet that contained CALTP; the proportion of medium-chain fatty acids (c10-c16) and free fatty acids was lower compared to the diet (CON). While the proportion of unsaturated fatty acids (UFA) in the diet increased CALTP. Therefore, the inclusion of CALTP in the diet is helpful because it has a positive impact on the composition of milk and mature cheese, reduces the cost of the diet and helps recycle byproducts.

A novel hepatocyte ketone production assay to help the selection of nutrients for the ketogenic diet treatment of epilepsy

The classic ketogenic diet is an effective treatment option for drug-resistant epilepsy, but its high fat content challenges patient compliance. Optimizing liver ketone production guided by a method comparing substrates for their ketogenic potential may help to reduce the fat content of the diet without loss in ketosis induction. Here, we present a liver cell assay measuring the β-hydroxybutyrate (βHB) yield from fatty acid substrates. Even chain albumin-conjugated fatty acids comprising between 4 and 18 carbon atoms showed a sigmoidal concentration-βHB response curve (CRC) whereas acetate and omega-3 PUFAs produced no CRC. While CRCs were not distinguished by their half-maximal effective concentration (EC50), they differed by maximum response, which related inversely to the carbon chain length and was highest for butyrate. The assay also suitably assessed the βHB yield from fatty acid blends detecting shifts in maximum response from exchanging medium chain fatty acids for long chain fatty acids. The assay further detected a dual role for butyrate and hexanoic acid as ketogenic substrate at high concentration and ketogenic enhancer at low concentration, augmenting the βHB yield from oleic acid and a fatty acid blend. The assay also found propionate to inhibit ketogenesis from oleic acid and a fatty acid blend at low physiological concentration. Although the in vitro assay shows promise as a tool to optimize the ketogenic yield of a fat blend, its predictive value requires human validation.

Comparative Analysis of Chemical Descriptors by Machine Learning Reveals Atomistic Insights into Solute-Lipid Interactions.

This study explores the research area of drug solubility in lipid excipients, an area persistently complex despite recent advancements in understanding and predicting solubility based on molecular structure. To this end, this research investigated novel descriptor sets, employing machine learning techniques to understand the determinants governing interactions between solutes and medium-chain triglycerides (MCTs). Quantitative structure-property relationships (QSPR) were constructed on an extended solubility data set comprising 182 experimental values of structurally diverse drug molecules, including both development and marketed drugs to extract meaningful property relationships. Four classes of molecular descriptors, ranging from traditional representations to complex geometrical descriptions, were assessed and compared in terms of their predictive accuracy and interpretability. These include two-dimensional (2D) and three-dimensional (3D) descriptors, Abraham solvation parameters, extended connectivity fingerprints (ECFPs), and the smooth overlap of atomic position (SOAP) descriptor. Through testing three distinct regularized regression algorithms alongside various preprocessing schemes, the SOAP descriptor enabled the construction of a superior performing model in terms of interpretability and accuracy. Its atom-centered characteristics allowed contributions to be estimated at the atomic level, thereby enabling the ranking of prevalent molecular motifs and their influence on drug solubility in MCTs. The performance on a separate test set demonstrated high predictive accuracy (RMSE = 0.50) for 2D and 3D, SOAP, and Abraham Solvation descriptors. The model trained on ECFP4 descriptors resulted in inferior predictive accuracy. Lastly, uncertainty estimations for each model were introduced to assess their applicability domains and provide information on where the models may extrapolate in chemical space and, thus, where more data may be necessary to refine a data-driven approach to predict solubility in MCTs. Overall, the presented approaches further enable computationally informed formulation development by introducing a novel in silico approach for rational drug development and prediction of dose loading in lipids.