Combined administration of lauric acid and glucose improved cancer-derived cardiac atrophy in a mouse cachexia model.

Cancer-derived myocardial damage is an important cause of death in cancer patients. However, the development of dietary interventions for treating such damage has not been advanced. Here, we investigated the effect of dietary intervention with lauric acid (LAA) and glucose, which was effective against skeletal muscle sarcopenia in a mouse cachexia model, on myocardial damage. Treatment of H9c2 rat cardiomyoblasts with lauric acid promoted mitochondrial respiration and increased ATP production by Seahorse flux analysis, but did not increase oxidative stress. Glycolysis was also promoted by LAA. In contrast, mitochondrial respiration and ATP production were suppressed, and oxidative stress was increased in an in vitro cachexia model in which cardiomyoblasts were treated with mouse cachexia ascites. Ascites-treated H9c2 cells with concurrent treatment with LAA and high glucose showed that mitochondrial respiration and glycolysis were promoted more than that of the control, and ATP was restored to the level of the control. Oxidative stress was also reduced by the combined treatment. In the mouse cachexia model, myocardiac atrophy and decreased levels of a marker of muscle maturity, SDS-soluble MYL1, were observed. When LAA in CE-2 diet was orally administered alone, no significant rescue was observed in the cancer-derived myocardial disorder. In contrast, combined oral administration of LAA and glucose recovered myocardial atrophy and MYL1 to levels observed in the control without increase in the cancer weight. Therefore, it is suggested that dietary intervention using a combination of LAA and glucose for cancer cachexia might improve cancer-derived myocardial damage.

Effects of intraduodenal coadministration of lauric acid and leucine on gut motility, plasma cholecystokinin, and energy intake in healthy men.

The fatty acid, lauric acid (C12), and the amino acid, leucine (Leu) stimulate gut hormones, including CCK, associated with suppression of energy intake. In our recent study, intraduodenal infusion of a combination of C12 and l-tryptophan, at loads that individually did not affect energy intake, reduced energy intake substantially, associated with much greater stimulation of CCK. We have now investigated whether combined administration of C12 and Leu would enhance the intake-suppressant effects of each nutrient, when given at loads that each suppress energy intake individually. Sixteen healthy, lean males (age: 23 ± 2 yr) received, in randomized, double-blind fashion, 90-min intraduodenal infusions of control (saline), C12 (0.4 kcal/min), Leu (0.45 kcal/min), or C12+Leu (0.85 kcal/min). Antropyloroduodenal pressures were measured continuously and plasma CCK at 15-min intervals, and energy intake from a standardized buffet-meal, consumed immediately postinfusion, was quantified. All nutrient infusions stimulated plasma CCK compared with control (P < 0.05). Moreover, C12 and C12+Leu stimulated CCK compared with Leu (P < 0.05) (mean concentration, pmol/L; control: 2.3 ± 0.3, C12: 3.8 ± 0.3, Leu: 2.7 ± 0.3, and C12+Leu: 4.0 ± 0.4). C12+Leu, but not C12 or Leu, stimulated pyloric pressures (P < 0.05). C12+Leu and C12 reduced energy intake (P < 0.05), and there was a trend for Leu to reduce (P = 0.06) energy intake compared with control, with no differences between the three nutrient treatments (kcal; control: 1398 ± 84, C12: 1226 ± 80, Leu: 1260 ± 92, and C12+Leu: 1208 ± 83). In conclusion, combination of C12 and Leu, at the loads given, did not reduce energy intake beyond their individual effects, possibly because maximal effects had been evoked.

Giving combined medium-chain fatty acids and glucose protects against cancer-associated skeletal muscle atrophy.

Skeletal muscle volume is associated with prognosis of cancer patients. Maintenance of skeletal muscle is an essential concern in cancer treatment. In nutritional intervention, it is important to focus on differences in metabolism between tumor and skeletal muscle. We examined the influence of oral intake of glucose (0%, 10%, 50%) and 2% medium-chain fatty acid (lauric acid, LAA, C12:0) on tumor growth and skeletal muscle atrophy in mouse peritoneal metastasis models using CT26 mouse colon cancer cells and HT29 human colon cancer cells. After 2 weeks of experimental breeding, skeletal muscle and tumor were removed and analyzed. Glucose intake contributed to prevention of skeletal muscle atrophy in a sugar concentration-dependent way and also promoted tumor growth. LAA ingestion elevated the level of skeletal muscle protein and suppressed tumor growth by inducing tumor-selective oxidative stress production. When a combination of glucose and LAA was ingested, skeletal muscle mass increased and tumor growth was suppressed. Our results confirmed that although glucose is an important nutrient for the prevention of skeletal muscle atrophy, it may also foster tumor growth. However, the ingestion of LAA inhibited tumor growth, and its combination with glucose promoted skeletal muscle integrity and function, without stimulating tumor growth. These findings suggest novel strategies for the prevention of skeletal muscle atrophy.

Early postnatal treatment with soluble epoxide hydrolase inhibitor or 15-deoxy-Δ(12,14)-prostagandin J2 prevents prenatal dexamethasone and postnatal high saturated fat diet induced programmed hypertension in adult rat offspring.

Prenatal dexamethasone (DEX) exposure, postnatal high-fat (HF) intake, and arachidonic acid pathway are closely related to hypertension. We tested whether a soluble epoxide hydrolase (SEH) inhibitor, 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) or 15-deoxy-Δ(12,14)-prostagandin J2 (15dPGJ2) therapy can rescue programmed hypertension in the DEX+HF two-hit model. Four groups of Sprague Dawley rats were studied: control, DEX+HF, AUDA, and 15dPGJ2. Dexamethasone (0.1mg/kg body weight) was intraperitoneally administered to pregnant rats from gestational day 16-22. Male offspring received high-fat diet (D12331, Research Diets) from weaning to 4 months of age. In AUDA group, mother rats received 25mg/L in drinking water during lactation. In the 15dPGJ2 group, male offspring received 15dPGJ2 1.5mg/kg BW by subcutaneous injection once daily for 1 week after birth. We found postnatal HF diet aggravated prenatal DEX-induced programmed hypertension, which was similarly prevented by early treatment with AUDA or 15dPGJ2. The beneficial effects of AUDA and 15d-PGJ2 therapy include inhibition of SEH, increases of renal angiotensin converting enzyme-2 (ACE2) and angiotensin II type 2 receptor (AT2R) protein levels, and restoration of nitric oxide bioavailability. Better understanding of the impact of arachidonic acid pathway in the two-hit model will help prevent programmed hypertension in children exposed to corticosteroids and postnatal HF intake.

Different oral sensitivities to and sensations of short-, medium-, and long-chain fatty acids in humans.

Fatty acids that vary in chain length and degree of unsaturation have different effects on metabolism and human health. As evidence for a "taste" of nonesterified fatty acids (NEFA) accumulates, it may be hypothesized that fatty acid structures will also influence oral sensations. The present study examined oral sensitivity to caproic (C6), lauric (C12), and oleic (C18:1) acids over repeated visits. Analyses were also conducted on textural properties of NEFA emulsions and blank solutions. Oral thresholds for caproic acid were lower compared with oleic acid. Lauric acid thresholds were intermediate but not significantly different from either, likely due to lingering irritating sensations that prevented accurate discrimination. From particle size analysis, larger droplets were observed in blank solutions when mineral oil was used, leading to instability of the emulsion, which was not observed when emulsions contained NEFA or when mineral oil was removed from the blank. Rheological data showed no differences in viscosity among samples except for a slightly higher viscosity with oleic acid concentrations above 58 mM. Thus, texture was unlikely to be the property used to distinguish between the samples. Differences in oral detection and sensation of caproic, lauric, and oleic acids may be due to different properties of the fatty acid alkyl chains.

Attenuation of responses to endotoxin by the triggering receptor expressed on myeloid cells-1 inhibitor LR12 in nonhuman primate.

BACKGROUND: The triggering receptor expressed on myeloid cells-1 is an immunoreceptor that amplifies the inflammatory response mediated by toll-like receptors engagement. Triggering receptor expressed on myeloid cells-1 inhibitory peptides such LR12 have been shown to prevent hyperresponsiveness and death in several experimental models of septic shock. METHODS: Twelve adult male Cynomolgus (Macaca fascicularis) monkeys exposed to an intravenous bolus of endotoxin (10 µg/kg) were randomized to receive LR12 or placebo (n = 6 per group) as an initial intravenous bolus followed by an 8-h continuous intravenous infusion. An additional group of four only received vehicle infusion. Vital signs were monitored for 8 h. Blood was sampled at H0, 1, 2, 4, and 8 for analysis of clinical chemistries, leukocyte count, coagulation parameters, and cytokine plasma concentration. RESULTS: LR12 showed no effect on heart rate and body temperature. By contrast to the placebo group, which experienced a 25 to 40% blood pressure decrease after endotoxin administration, LR12-treated monkeys remained normotensive. Endotoxin induced leukopenia at 2 h (mean leukocyte count, 7.62 g/l vs. 21.1 at H0), which was attenuated by LR12. LR12 also attenuated cytokine production. CONCLUSIONS: The triggering receptor expressed on myeloid cells-1 inhibitor LR12 is able to mitigate endotoxin-associated clinical and biological alterations, with no obvious side effects. This study paves the way for future phases Ia and Ib trials in humans.

Effects of feeding lauric acid or coconut oil on ruminal protozoa numbers, fermentation pattern, digestion, omasal nutrient flow, and milk production in dairy cows.

The objectives of this study were to evaluate the feeding of coconut oil (CO), in which lauric acid (La) comprises about 50% of the fatty acid composition, as a practical rumen protozoa (RP) suppressing agent, to assess whether the source of La affects ruminal fermentation and animal performance and to test whether suppressing RP improves N utilization, nutrient digestion, nutrient flow at the omasal canal, and milk production. Fifteen multiparous Holstein cows (3 fitted with ruminal cannulas) and 15 primiparous Holstein cows (3 fitted with ruminal cannulas) were used in a replicated 3×3 Latin square experiment with 14d of adaptation and 14d of sample collection. Diets were fed as total mixed ration and contained (dry matter basis) 10% corn silage, 50% alfalfa silage, and 40% concentrate. The control diet contained 3% (dry matter basis) calcium soaps of palm oil fatty acids (Megalac, Church & Dwight Co. Inc., Princeton, NJ) as a ruminally inert fat source and had no added La or CO. Diets with La and CO were formulated to contain equal amounts of La (1.3%, dry matter basis). Dry matter intake was not affected by treatment. Both CO and La reduced RP numbers by about 40%. Lauric acid reduced yield of milk and milk components; however, CO did not affect yield of milk and yields of milk components. Both La and CO caused small reductions in total VFA concentration; CO increased molar proportion of ruminal propionate, reduced ruminal ammonia and branched-chain volatile fatty acids, suggesting reduced protein degradation, and reduced milk urea N and blood urea N concentrations, suggesting improved protein efficiency. Lauric acid reduced total-tract apparent digestibility of neutral detergent fiber and acid detergent fiber as well as ruminal apparent digestibility of neutral detergent fiber and acid detergent fiber as measured at the omasal canal; however, CO did not alter fiber digestion. Microbial protein flow at the omasal canal, as well as the flow of N fractions at the omasal canal, did not differ among treatments. Results from this experiment have confirmed that dietary La is not a practical agent for suppressing RP population in dairy cows, mainly because of its negative effects on fiber digestion and ruminal fermentation. Intake of CO appeared to reduce ruminal and improve protein efficiency, but did not improve milk production, milk composition, or increase microbial outflow from the rumen. Based on the results of this study, a 40% reduction of RP population is not sufficient to improve N utilization in dairy cows.

Topical surfactant-induced pruritus: involvement of histamine released from epidermal keratinocytes.

Surfactants, an important component of cleansers, often cause itch in humans. Topical application of sodium laurate and N-lauroylsarcosine sodium salt to the skin of mice immediately (for 1-1.5 hours) increased scratching, and the former increased scratching again between 2 and 3 hours after application. Thus, we examined the mechanisms of sodium laurate-induced delayed scratching. Sodium laurate (0.1%-10%) increased delayed scratching and skin surface pH in a concentration-dependent manner. N-lauroylsarcosine sodium salt had no effect on these parameters, and sodium hydroxide solution did not increase delayed scratching. Sodium laurate-induced delayed scratching was markedly inhibited by the H(1) histamine receptor antagonist terfenadine, but it was not affected by mast cell deficiency. Sodium laurate application had no effect on the number of total and degranulated mast cells, and did not induce plasma extravasation or the infiltration of inflammatory cells in the skin. Sodium laurate application increased the histamine content of the epidermis, but not that of the dermis, in normal and mast cell-deficient mice. Sodium laurate application increased the ratio of 53-kDa l-histidine decarboxylase (HDC, a key enzyme for histamine production) to 74-kDa HDC in the mouse epidermis and in a human keratinocyte culture. Sodium laurate increased histamine in the human keratinocyte culture, without affecting cell viability. The present results suggest that sodium laurate induced delayed scratching at an alkaline pH through the increased production of histamine in keratinocytes, which may be due to enhanced processing of 74-kDa to 53-kDa HDC.

Prevention of topical surfactant-induced itch-related responses by chlorogenic acid through the inhibition of increased histamine production in the epidermis.

Effects of chlorogenic acid on surfactant-induced itching were studied in mice. Topical application of sodium laurate increased hind-paw scratching, an itch-related response, 2 h after application, which was inhibited by topical post-treatment with chlorogenic acid. Sodium laurate increased the histamine content and 53-kDa L-histidine decarboxylase in the epidermis, which were also inhibited by post-treatment with chlorogenic acid. These results suggest that topical chlorogenic acid is effective in the prevention of itching induced by anionic surfactants. The inhibitory activity of chlorogenic acid may be due to the inhibition of an increase in histamine in the epidermis.

Soluble epoxide hydrolase inhibition improves myocardial perfusion and function in experimental heart failure.

The study addressed the hypothesis that soluble epoxide hydrolase (sEH) inhibition, which increases cardiovascular protective epoxyeicosatrienoic acids (EETs), exerts beneficial effects in an established chronic heart failure (CHF) model. In CHF rats, left ventricular (LV) function, perfusion and remodeling were assessed using MRI and invasive hemodynamics after 42-day (starting 8 days after coronary ligation) and delayed 3-day (starting 47 days after coronary ligation) treatments with the sEH inhibitor AUDA (twice 0.25 mg/day). Delayed 3-day and 42-day AUDA increased plasma EETs demonstrating the effective inhibition of sEH. Delayed 3-day and 42-day AUDA enhanced cardiac output without change in arterial pressure, thus reducing total peripheral resistance. Both treatment periods increased the slope of the LV end-systolic pressure-volume relation, but only 42-day AUDA decreased LV end-diastolic pressure, relaxation constant Tau and the slope of the LV end-diastolic pressure-volume relation, associated with a reduced LV diastolic volume and collagen density. Delayed 3-day and, to a larger extent, 42-day AUDA increased LV perfusion associated with a decreased LV hypoxia-inducible factor-1alpha. Both treatment periods decreased reactive oxygen species level and increased reduced-oxidized glutathione ratio. Finally, MSPPOH, an inhibitor of the EET-synthesizing enzyme cytochrome epoxygenases, abolished the beneficial effects of 3-day AUDA on LV function and perfusion. Augmentation of EET availability by pharmacological inhibition of sEH increases LV diastolic and systolic functions in established CHF. This notably results from short-term processes, i.e. increased LV perfusion, reduced LV oxidative stress and peripheral vasodilatation, but also from long-term effects, i.e. reduced LV remodeling.

Link between lipid metabolism and voluntary food intake in rainbow trout fed coconut oil rich in medium-chain TAG.

We examined the long-term effect of feeding coconut oil (CO; rich in lauric acid, C12) on voluntary food intake and nutrient utilisation in rainbow trout (Oncorhynchus mykiss), with particular attention to the metabolic use (storage or oxidation) of ingested medium-chain TAG. Trout were fed for 15 weeks one of the four isoproteic diets containing fish oil (FO) or CO as fat source (FS), incorporated at 5% (low fat, LF) or 15% (high fat, HF). Fat level or FS did not modify food intake (g/kg(0·8) per d), despite higher intestinal cholecystokinin-T mRNA in trout fed the HF-FO diet. The HF diets relative to the LF ones induced higher growth and adiposity, whereas the replacements of FO by CO resulted in similar growth and adiposity. This, together with the substantial retention of C12 (57% of intake), suggests the relatively low oxidation of ingested C12. The down-regulation of carnitine palmitoyl-transferase-1 (CPT-1) confirms the minor dependency of medium-chain fatty acids (MCFA) on CPT-1 to enter the mitochondria. However, MCFA did not up-regulate mitochondrial oxidation evaluated using hepatic hydroxyacyl-CoA dehydrogenase as a marker, in line with their high retention in body lipids. At a low lipid level, MCFA increased mRNA levels of fatty acid synthase, elongase and stearoyl-CoA desaturase in liver, showing the hepatic activation of fatty acid synthesis pathways by MCFA, reflected by increased 16 : 0, 18 : 0, 16 : 1, 18 : 1 body levels. The high capacity of trout to incorporate and transform C12, rather than to readily oxidise C12, contrasts with data in mammals and may explain the absence of a satiating effect of CO in rainbow trout.

Activity of virgin coconut oil, lauric acid or monolaurin in combination with lactic acid against Staphylococcus aureus.

The objective of this study was to investigate the in vitro activities of virgin coconut oil, lauric acid and monolaurin in combination with lactic acid against two strains of Staphylococcus aureus, ATCC 25923 and an isolate from a pig carcass, by determination of Fractional Bactericidal Concentration Index (FBCI), time-kill method, as well as scanning and transmission electron microscopy. Minimum bactericidal concentrations (MBC) of lauric acid, monolaurin and lactic acid were 3.2 mg/ml, 0.1 mg/ml and 0.4% (v/v), respectively. The effects of lauric acid + lactic acid and monolaurin + lactic acid combinations were synergistic against both strains, exhibiting FBCIs of 0.25 and 0.63, respectively. In time-kill studies, lauric acid and monolaurin + lactic acid combinations added at their minimum inhibitory concentrations produced a bactericidal effect. The induction of stress in non-stressed cells was dependent on the type and concentration of antimicrobial. This resulted in a loss and change of the cytoplasm and membrane in cells of the bacterium. In contrast, virgin coconut oil (10%) was not active against S. aureus. The bacterial counts found in pork loin treated with lauric acid and monolaurin alone were significantly higher (p <0.05) than those treated with both lipids in combination with lactic acid at sub-inhibitory concentrations. The color, odor and overall acceptability of the pork loins were adversely affected by treatment with the three lipids and lactic acid alone but when combinations of the agents were used the sensory quality was acceptable.

The chain length of dietary saturated fatty acids affects human postprandial lipemia.

OBJECTIVE: Saturated fats increase total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C) and are linked to coronary artery disease risk. The effect of variance in chain length of saturated fatty acids (SFA) on coronary artery disease in human postprandial lipemia is not well elucidated. METHODS: A total of 20 healthy volunteers were challenged with 3 test meals, similar in fat content (~31% en) but varying in saturated SFA content and polyunsaturated/saturated fatty acid ratios (P/S). The 3 meals were lauric + myristic acid-rich (LM), P/S 0.19; palmitic acid-rich (POL), P/S 0.31; and stearic acid-rich (STE), P/S 0.22. Blood was sampled at fasted baseline and 2, 4, 5, 6, and 8 hours. Plasma lipids (triacylglycerol [TAG]) and lipoproteins (TC, LDL-C, high density lipoprotein-cholesterol [HDL-C]) were evaluated. RESULTS: Varying SFA in the test meal significantly impacted postprandial TAG response (p < 0.05). Plasma TAG peaked at 5 hours for STE, 4 hours for POL, and 2 hours for LM test meals. Area-under-the-curve (AUC) for plasma TAG was increased significantly after STE treatment (STE > LM by 32.2%, p = 0.003; STE > POL by 27.9%, p = 0.023) but was not significantly different between POL and LM (POL > LM by 6.0%, p > 0.05). At 2 hours, plasma HDL-C increased significantly after the LM and POL test meals compared with STE (p < 0.05). In comparison to the STE test meal, HDL-C AUC was elevated 14.0% (p = 0.005) and 7.6% (p = 0.023) by the LM and POL test meals, respectively. The TC response was also increased significantly by LM compared with both POL and STE test meals (p < 0.05). CONCLUSIONS: Chain length of saturates clearly mediated postmeal plasma TAG and HDL-C changes.

Effects of a combination of feed additives on methane production, diet digestibility, and animal performance in lactating dairy cows.

Two experiments were conducted to assess the effects of a mixture of dietary additives on enteric methane production, rumen fermentation, diet digestibility, energy balance, and animal performance in lactating dairy cows. Identical diets were fed in both experiments. The mixture of feed additives investigated contained lauric acid, myristic acid, linseed oil, and calcium fumarate. These additives were included at 0.4, 1.2, 1.5, and 0.7% of dietary dry matter, respectively (treatment ADD). Experimental fat sources were exchanged for a rumen inert source of fat in the control diet (treatment CON) to maintain isolipidic rations. Cows (experiment 1, n=20; experiment 2, n=12) were fed restricted amounts of feed to avoid confounding effects of dry matter intake on methane production. In experiment 1, methane production and energy balance were studied using open-circuit indirect calorimetry. In experiment 2, 10 rumen-fistulated animals were used to measure rumen fermentation characteristics. In both experiments animal performance was monitored. The inclusion of dietary additives decreased methane emissions (g/d) by 10%. Milk yield and milk fat content tended to be lower for ADD in experiment 1. In experiment 2, milk production was not affected by ADD, but milk fat content was lower. Fat- and protein-corrected milk was lower for ADD in both experiments. Milk urea nitrogen content was lowered by ADD in experiment 1 and tended to be lower in experiment 2. Apparent total tract digestibility of fat, but not that of starch or neutral detergent fiber, was higher for ADD. Energy retention did not differ between treatments. The decrease in methane production (g/d) was not evident when methane emission was expressed per kilogram of milk produced. Feeding ADD resulted in increases of C12:0 and C14:0 and the intermediates of linseed oil biohydrogenation in milk in both experiments. In experiment 2, ADD-fed cows tended to have a decreased number of protozoa in rumen fluid when compared with that in control cows. Total volatile fatty acid concentrations were lower for ADD, whereas molar proportions of propionate increased at the expense of acetate and butyrate.

Influence of chemical permeation enhancers on transdermal permeation of alfuzosin: an investigation using response surface modeling.

CONTEXT: A nonoral alternative such as transdermal system is desired to improve bioavailability and to maintain a constant and prolonged drug level with reduced frequency of dosing. OBJECTIVE: The objective of the investigation is to develop a transdermal therapeutic system for alfuzosin hydrochloride and to study the influence of chemical permeation enhancers (CPEs) on the percutaneous permeation pattern. MATERIAL AND METHODS: A D-optimal mixture design was used to study the influence of CPE with oleic acid (OA), lauric acid, and propylene glycol (PG) as mixture components. The influence of chemical enhancers on skin permeation was compared using one-way analysis of variance followed by multiple comparison analysis. Criterion of desirability was used to optimize the therapeutic system. Preclinical studies in rabbits were also carried out to establish an ex vivo-in vivo correlation (EVIVC). RESULTS: The drug permeation pattern suggested Higuchian diffusion as predominant mode followed by case II to super case II transport as drug transport mechanism. The optimized formulation was obtained using 5% (w/w) CPE consisting of a blend of 62.41% OA and 37.59% PG. About twofold increase in alfuzosin permeation was achieved with the optimized transdermal patch. An approximate linear EVIVC was established (R(2) = 0.971). DISCUSSION: The optimized blend of enhancers could improve skin permeation parameters. A higher extent of in vivo skin permeation compared with cadaver skin permeation may be due to more permeable nature of rabbit skin. CONCLUSION: The investigations suggest an effective alternative delivery strategy such as transdermal systems for alfuzosin hydrochloride.

Dietary Saturated Fatty Acids Modulate Pain Behaviour in Trauma-Induced Osteoarthritis in Rats.

Osteoarthritis (OA) is a degenerative condition of joints, causing pain and swelling, and can be caused or worsened by trauma and obesity. The objectives of this study were to determine whether pain behaviour and progression of OA were increased in rats with trauma-induced OA fed dietary saturated fatty acids (SFA). Male Wistar rats were fed either a corn starch diet (C) or high-carbohydrate high-fat diet (H) with either 20% beef tallow or SFA (lauric (HLA), myristic (HMA), palmitic (HPA) or stearic (HSA) acids) for 16 weeks prior to and 8 weeks after excision of the medial meniscus of right knee joint to initiate OA when pain behaviour, glial activity, progression of knee OA, inflammatory mediators and signs of metabolic syndrome were assessed. Rats fed beef tallow, palmitic or stearic acids showed increased pain symptoms characterised by decreased hind paw/limb withdrawal thresholds and grip strengths and increased spinal astrogliosis and microgliosis compared to rats fed lauric or myristic acids. However, the severity of OA joint damage was unchanged by these dietary manipulations. We conclude that pain symptoms of trauma-induced OA in rats worsen with increased dietary beef tallow or palmitic or stearic acids, but improve with lauric or myristic acids, despite unchanged OA cartilage damage.

Dietary Supplementation of Lauric Acid Alleviates the Irregular Estrous Cycle and the Impaired Metabolism and Thermogenesis in Female Mice Fed with High-Fat Diet (HFD).

Lauric acid (LA) has been implicated in the prevention/treatment of obesity. However, the role of LA in modulating an obesity-related female reproductive disorder remains largely unknown. Here, female mice were fed a control diet, high-fat diet (HFD), or HFD supplemented with 1% LA. The results demonstrated that the HFD-induced estrous cycle irregularity and the reduction of serum follicle-stimulating hormone (FSH) were alleviated by LA supplementation. In possible mechanisms, LA supplementation led to significant increase in serum lipid metabolites such as sphingomyelin and lysophosphatidylcholine containing LA (C12:0) and the improvement of glucose metabolism in mice fed HFD. Moreover, impaired body energy metabolism and weakened brown adipose tissue (BAT) thermogenesis of HFD-fed mice were improved by LA supplementation. Together, these findings showed that LA supplementation alleviated HFD-induced estrous cycle irregularity, possibly associated with altered serum lipid metabolites, improved glucose metabolism, body energy metabolism, and BAT thermogenesis. These findings suggested the potential application of LA in alleviating obesity and its related reproductive disorders.

Effects of Medium Chain Fatty Acids on Intestinal Health of Monogastric Animals.

Medium-chain fatty acids (MCFAs) are the main form of Medium Chain Triglycerides (MCTs) utilized by monogastric animals. MCFAs can be directly absorbed and supply rapid energy to promote the renewal and repair of intestinal epithelial cells, maintain the integrity of intestinal mucosal barrier function, and reduce inflammation and stress. In our review, we pay more attention to the role of MCFAs on intestinal microbiota and mucosa immunity to explore MCFA's positive effect. It was found that MCFAs and their esterified forms can decrease pathogens while increasing probiotics. In addition, being recognized via specific receptors, MCFAs are capable of alleviating inflammation to a certain extent by regulating inflammation and immune-related pathways. MCFAs may also have a certain value to relieve intestinal allergy and inflammatory bowel disease (IBD). Unknown mechanism of various MCFA characteristics still causes dilemmas in the application, thus MCFAs are used generally in limited dosages and combined with short-chain organic acids (SOAs) to attain ideal results. We hope that further studies will provide guidance for the practical use of MCFAs in animal feed.

Effects of Duodenal Infusion of Lauric Acid and L-Tryptophan, Alone and Combined, on Fasting Glucose, Insulin and Glucagon in Healthy Men.

The fatty acid, lauric acid ('C12'), and the amino acid, tryptophan ('Trp'), when given intraduodenally at loads that individually do not affect energy intake, have recently been shown to stimulate plasma cholecystokinin, suppress ghrelin and reduce energy intake much more markedly when combined. Both fatty acids and amino acids stimulate insulin secretion by distinct mechanisms; fatty acids enhance glucose-stimulated insulin secretion, while amino acids may have a direct effect on pancreatic ß cells. Therefore, it is possible that, by combining these nutrients, their effects to lower blood glucose may be enhanced. We have investigated the potential for the combination of C12 and Trp to have additive effects to reduce blood glucose. To address this question, plasma concentrations of glucose, insulin and glucagon were measured in 16 healthy, lean males during duodenal infusions of saline (control), C12 (0.3 kcal/min), Trp (0.1 kcal/min), or C12+Trp (0.4 kcal/min), for 90 min. Both C12 and C12+Trp moderately reduced plasma glucose compared with control (p < 0.05). C12+Trp, but not C12 or Trp, stimulated insulin and increased the insulin-to-glucose ratio (p < 0.05). There was no effect on plasma glucagon. In conclusion, combined intraduodenal administration of C12 and Trp reduced fasting glucose in healthy men, and this decrease was driven primarily by C12. The effects of these nutrients on postprandial blood glucose and elevated fasting blood glucose in type 2 diabetes warrant evaluation.

Inhibition of soluble epoxide hydrolase regulates monocyte/macrophage polarization and improves neurological outcome in a rat model of ischemic stroke.

It is generally understood that continuing neuroinflammation after ischemic stroke can exacerbate the brain damage. During the inflammatory hematogenous recruitment process, the monocytes and macrophages are activated into proinflammatory M1 and anti-inflammatory M2 cell types. Inhibition of soluble epoxide hydrolase (sEH) activity has been reported to regulate monocytes/macrophages, and attenuates neuroinflammation. This study aimed to evaluate whether a selective sEH inhibitor, 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), can regulate monocyte/macrophage polarization and improve motor function in the rats with ischemic stroke induced by middle cerebral artery occlusion. We measured the infarct volume with 2,3,5-triphenyltetrazolium chloride staining and used the rotarod test to assess motor performance in rats. The monocyte/macrophage activation and mRNA expression of proinflammatory mediators were measured by flow cytometry and reverse-transcription quantitative PCR, respectively. Our results showed better neurological function and less infarct volume in the rats treated with AUDA. Compared with the vehicle group, the AUDA-treated group showed a reduction in M1 monocyte/macrophage activation and proinflammatory mRNA expressions in the infarct cortex of rats. Our data suggest that the sEH inhibition may regulate monocyte/macrophage polarization and improve neurological outcome after ischemic stroke.