The Inhibition of Metabolic Inflammation by EPA Is Associated with Enhanced Mitochondrial Fusion and Insulin Signaling in Human Primary Myotubes.

BACKGROUND: Sustained fuel excess triggers low-grade inflammation that can drive mitochondrial dysfunction, a pivotal defect in the pathogenesis of insulin resistance in skeletal muscle. OBJECTIVES: This study aimed to investigate whether inflammation in skeletal muscle can be prevented by EPA, and if this is associated with an improvement in mitochondrial fusion, membrane potential, and insulin signaling. METHODS: Human primary myotubes were treated for 24 h with palmitic acid (PA, 500 µM) under hyperglycemic conditions (13 mM glucose), which represents nutrient overload, and in the presence or absence of EPA (100 µM). After the treatments, the expression of peroxisome proliferator-activated receptor γ coactivator 1-α (PPARGC1A) and IL6 was assessed by q-PCR. Western blot was used to measure the abundance of the inhibitor of NF-κB (IKBA), mitofusin-2 (MFN2), mitochondrial electron transport chain complex proteins, and insulin-dependent AKT (Ser473) and AKT substrate 160 (AS 160; Thr642) phosphorylation. Mitochondrial dynamics and membrane potential were evaluated using immunocytochemistry and the JC-1 (tetraethylbenzimidazolylcarbocyanine iodide) dye, respectively. Data were analyzed using 1-factor ANOVA followed by Tukey post hoc test. RESULTS: Nutrient excess activated the proinflammatory NFκB signaling marked by a decrease in IKBA (40%; P < 0.05) and the upregulation of IL6 mRNA (12-fold; P < 0.001). It also promoted mitochondrial fragmentation (53%; P < 0.001). All these effects were counteracted by EPA. Furthermore, nutrient overload-induced drop in mitochondrial membrane potential (6%; P < 0.05) was prevented by EPA. Finally, EPA inhibited fuel surplus-induced impairment in insulin-mediated phosphorylation of AKT (235%; P < 0.01) and AS160 (49%; P < 0.05). CONCLUSIONS: EPA inhibited NFκB signaling, which was associated with an attenuation of the deleterious effects of PA and hyperglycemia on both mitochondrial health and insulin signaling in human primary myotubes. Thus, EPA might preserve skeletal muscle metabolic health during sustained fuel excess but this requires confirmation in human clinical trials.

Effects of Antihypertensive Agents on Intestinal Contractility in the Spontaneously Hypertensive Rat: Angiotensin Receptor System Downregulation by Losartan.

Hypertension is an inflammatory condition controlled by the renin angiotensin system and is linked to kidney disease, diabetes mellitus, and recently to dysfunction of the gut. The aim of this study was to determine what effect antihypertensive drug treatments may have on intestinal function of the spontaneously hypertensive rat (SHR). In the first experiment, SHRs were treated with enalapril, hydralazine, or with no treatment as a control. In the second experiment, SHRs were treated with losartan or with no treatment as a control. All drug treatments led to significant lowering of blood pressure after 16 weeks. At termination, intact tissue sections of the ileum and colon were induced to contract ex vivo by KCl; electrical stimulation; and agonists carbachol, angiotensin II, and prostaglandin E2 (PGE2). There were no differences in ileal or colonic contractility due to hydralazine or enalapril compared with no-treatment SHR control. However, for the ileum, the losartan group responded significantly more to KCl and carbachol while responding less to angiotensin II, with no difference for PGE2 compared with the no-treatment SHR control. In contrast, the colon responded similarly to KCl, electrical stimulation, and PGE2 but responded significantly less to angiotensin II. These results demonstrate that the ileum responds differently (with KCl and carbachol as agonists) to the colon after losartan treatment, whereas there is a reduced contractile response in both the ileum and colon following losartan treatment. Although there are few well documented major contraindications for angiotensin receptor blockers, the modulation of gut contractility by losartan may have wider implications for bowel health.

Microencapsulated krill and tuna oil blend raises plasma long-chain n-3 polyunsaturated fatty acid levels compared to tuna oil with similar increases in ileal contractility in rats.

Long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) may be more bioavailable from krill oil compared to fish oil due to their phospholipid structure. We tested whether a microencapsulated krill and tuna oil blend (ME-TOKO) provided greater LC n-3 PUFA bioavailability, improved blood lipid profiles and increased intestinal contractility compared to microencapsulated tuna oil (ME-TO). Rats were divided into three groups to receive isocaloric diets containing ME-TO, ME-TOKO and microencapsulated olive oil (ME-OO) at 0.3 or 2 g/100 g for 4 weeks. Final body and organ weights, feed intake and waste output were similar. ME-TOKO rats had higher plasma total LC n-3 PUFA levels compared to ME-TO, but liver LC n-3 PUFA levels and plasma triglyceride and cholesterol levels were similar in non-fasted rats. Diets containing 2% ME-TO and ME-TOKO also showed similar increases in ileal contractility. In summary, ME-TO bioavailability of LC n-3 PUFA was similar to ME-TOKO.

Inhibition of Angiotensin Converting Enzyme, Angiotensin II Receptor Blocking, and Blood Pressure Lowering Bioactivity across Plant Families.

Hypertension is a major risk factor for coronary heart disease, kidney disease, and stroke. Interest in medicinal or nutraceutical plant bioactives to reduce hypertension has increased dramatically. The main biological regulation of mammalian blood pressure is via the renin-angiotensin-aldosterone system. The key enzyme is angiotensin converting enzyme (ACE) that converts angiotensin I into the powerful vasoconstrictor, angiotensin II. Angiotensin II binds to its receptors (AT1) on smooth muscle cells of the arteriole vasculature causing vasoconstriction and elevation of blood pressure. This review focuses on the in vitro and in vivo reports of plant-derived extracts that inhibit ACE activity, block angiotensin II receptor binding and demonstrate hypotensive activity in animal or human studies. We describe 74 families of plants that exhibited significant ACE inhibitory activity and 16 plant families with potential AT1 receptor blocking activity, according to in vitro studies. From 43 plant families including some of those with in vitro bioactivity, the extracts from 73 plant species lowered blood pressure in various normotensive or hypertensive in vivo models by the oral route. Of these, 19 species from 15 families lowered human BP when administered orally. Some of the active plant extracts, isolated bioactives and BP-lowering mechanisms are discussed.

Cyanidin-3-rutinoside attenuates methylglyoxal-induced protein glycation and DNA damage via carbonyl trapping ability and scavenging reactive oxygen species.

BACKGROUND: Advanced glycation end-products (AGEs) play a significant role in the development and progression of vascular complication in diabetes. Anthocyanin has been recently reported to possess antiglycating activity. This study aimed to determine whether a naturally occurring anthocyanin, cyanidin-3-rutinoside (C3R) inhibits methylglyoxal (MG) induced protein glycation and oxidative protein and DNA damage. METHODS: C3R (0.125-1 mM) was incubated with bovine serum albumin and MG (1 mM) for 2 weeks. The formation of fluorescent AGEs was measured by using spectrofluorometer and thiol group content were used to detect protein oxidative damage. Gel electrophoresis was used to determine whether C3R (0.125-1 mM) reduced DNA strand breakage in a glycation model comprising lysine, MG and/or Cu(2+). The generation of superoxide anions and hydroxyl radicals were detected by the cytochrome c reduction assay and the thiobarbituric acid reactive substances assay. MG-trapping capacity was assessed by high performance liquid chromatography (HPLC). RESULTS: C3R (0.25-1 mM) reduced the formation of fluorescent AGEs and depleted protein thiol groups in bovine serum albumin mediated by MG. At 1 mM C3R inhibited oxidative DNA damage in the glycation model (p < 0.05) and at 0.5-1 mM prevented Cu(2+) induced DNA strand breakage in the presence of lysine and MG. The findings showed that C3R reduced the formation of superoxide anion and hydroxyl radicals during the glycation reaction of MG with lysine. C3R directly trapped MG in a concentration and time dependent manner (both p < 0.001). CONCLUSIONS: These findings suggest that C3R protects against MG-induced protein glycation and oxidative damage to protein and DNA by scavenging free radicals and trapping MG.

Bioequivalence of n-3 fatty acids from microencapsulated fish oil formulations in human subjects.

Fish oil n-3 fatty acids (FA) have known health benefits. Microencapsulation stabilises and protects fish oil from oxidation, enabling its incorporation into foods. The aim of the present study was to compare the bioavailability of n-3 FA delivered as two microencapsulated fish oil-formulated powders or fish oil gel capsules (FOGC) taken with a flavoured milk in healthy participants. Formulation 1 (F1) composed of a heated mixture of milk protein-sugar as an encapsulant, and formulation 2 (F2) comprised a heated mixture of milk protein-sugar-resistant starch as an encapsulant. Participants consumed 4 g fish oil (approximately 1·0 g EPA and DHA equivalent per dose). Bioavailability was assessed acutely after ingestion of a single dose by measuring total plasma FA composition over a period of 48 h (n 14) using a randomised cross-over design, and over the short term for a period of 4 weeks using an unblinded parallel design (after daily supplementation) by measuring total plasma and erythrocyte FA composition at baseline and at 2 and 4 weeks (n 47). In the acute study, F1 greatly increased (% Δ) plasma EPA and total n-3 FA levels at 2 and 4 h and DHA levels at 4 h compared with FOGC. The time to reach maximal plasma values (T(max)) was shorter for F1 than for FOGC or F2. In the short-term study, increases in plasma and erythrocyte n-3 FA values were similar for all treatments and achieved an omega-3 index in the range of 5·8-6·3 % after 4 weeks. Overall, the results demonstrated human bioequivalence for microencapsulated fish oil powder compared with FOGC.

Resistant starch alters colonic contractility and expression of related genes in rats fed a Western diet.

BACKGROUND AND AIM: Dietary fiber shortens gut transit time, but data on the effects of fiber components (including resistant starch, RS) on intestinal contractility are limited. We have examined RS effects in male Sprague-Dawley rats fed either a high-amylose maize starch (HAMS) or a wholemeal made from high-amylose wheat (HAW) on ileal and colonic contractility ex vivo and expression of genes associated with smooth muscle contractility. METHODS: Rats were fed diets containing 19 % fat, 20 % protein, and either low-amylose maize starch (LAMS), HAMS, wholemeal low-amylose wheat (LAW) or HAW for 11 week. Isolated ileal and proximal colonic sections were induced to contract electrically, or by receptor-independent (KCl) or receptor-dependent agents. Colonic gene expression was assessed using an Affymetrix microarray. RESULTS: Ileal contractility was unaffected by treatment. Maximal proximal colonic contractility induced electrically or by angiotensin II or carbachol was lower for rats fed HAMS and LAW relative to those fed LAMS (P < 0.05). The colonic expression of genes, including cholinergic receptors (Chrm2, Chrm3), serotonin receptors (Htr5a, Htr7), a protease-activated receptor (F2r), a prokineticin receptor (Prokr1), prokineticin (Prok1), and nitric oxide synthase 2 (Nos2), was altered by dietary HAMS relative to LAMS (P < 0.05). HAW did not significantly affect these genes or colonic contractility relative to effects of LAMS. CONCLUSIONS: RS and other fiber components could influence colorectal health through modulation of stool transit time via effects on muscular contractility.

Commentary on a trial comparing krill oil versus fish oil.

Considerable interest exists presently in comparing the performance of krill oil (KO) and fish oil (FO) supplements. Ramprasath et al. (Lipids Health Dis12:178, 2013) have recently compared use of KO and FO in a trial with healthy individuals to examine which oil is more effective in increasing n-3 PUFA, decreasing the n-6:n-3 ratio and improving the omega-3 index. The authors concluded that KO was more effective than FO for all three criteria. However, careful examination of the fatty acid profiles of the oils used showed that the FO used was not a typical FO; it contained linoleic acid as the dominant fatty acid (32%) and an n-6:n-3 ratio of >1. Due to the fatty acid profile being non-representative of typically commercially marketed FO, the conclusions presented by Ramrasath et al. (Lipids Health Dis12:178, 2013) are not justified and misleading. Considerable care is needed in ensuring that such comparative trials do not use inappropriate ingredients.

Molecular size fractions of bay leaf (Laurus nobilis) exhibit differentiated regulation of colorectal cancer cell growth in vitro.

Numerous in vitro studies using solvent or aqueous extracts of raw dietary plant material have demonstrated modulation of colon cancer cell growth and apoptosis and effects on immune and nonimmune pathways of inflammation. We have developed a generic, 3-staged food-compatible process involving heating for conversion of dietary plants into food ingredients and report results on potential colon cancer-regulating properties of processed forms of Bay leaf (Laurus nobilis). In vitro studies demonstrated inhibition of cancer cell growth by processed Bay leaf products in HT-29, HCT-116, Caco-2, and SW-480 human cancer cell lines, which were accompanied by variable levels of elevated apoptosis. Bay leaf also exerted moderate inhibition of cycloxygenase 2 and 5 lipoxygenase enzymatic activity. In addition, these extracts significantly downregulated interferon-γ production in T helper Type 1-stimulated whole blood from healthy donors. Furthermore, size fractionation of the extracts revealed that antiproliferative and proapoptotic activities were associated with low mass (primarily polyphenolics and essential oils) and high mass (primarily proteins including polyphenol oxidase) chemical classes, respectively. Bay leaf exerted in vitro bioactivity that might be relevant to protecting against early events in sporadic colorectal cancer, with potential for further optimization of bioactivity by size-based fractionation.

Dragon Fruit Peel Waste (Hylocereus undatus) as a Potential Ingredient for Reducing Lipid Peroxidation, Dietary Advanced Glycation End Products, and Starch Digestibility in Cookies.

Excessive consumption of cookies has been linked to harmful health outcomes owing to the presence of refined carbohydrates and heat-induced toxicants including end products of lipid peroxidation and dietary advanced glycation end products (dAGEs). To address this issue, this study explores the addition of dragon fruit peel powder (DFP), which is rich in phytochemicals and dietary fibers, to cookies as a potential solution to mitigate their adverse effects. The results indicate that adding DFP at 1%, 2%, and 5% w/w of raw cookie dough significantly improves the total phenolic and betacyanin contents and antioxidant activity, as evidenced by increased ferric-reducing antioxidant power. DFP incorporation also led to reductions in malondialdehyde and dAGEs (p < 0.05). Furthermore, the starch digestibility, hydrolysis index, and predicted glycemic index were all reduced in the presence of DFP, with the latter estimate being due to the higher content of undigested starch. Incorporating DFP in cookies resulted in significant changes in their physical properties, including texture and color. However, sensory evaluation indicates that the overall acceptability of the cookies was not negatively impacted by the addition of up to 2% DFP, suggesting that it is a viable option for enhancing the nutritional value of cookies without compromising their palatability. These findings suggest that DFP is a sustainable and healthier ingredient that can improve the antioxidant capacity of cookies while also mitigating the harmful effects of heat-induced toxins.

Dietary fish oil preserves cardiac function in the hypertrophied rat heart.

Regular fish or fish oil intake is associated with a low incidence of heart failure clinically, and fish oil-induced reduction in cardiac remodelling seen in hypertrophy models may contribute. We investigated whether improved cardiac energy efficiency in non-hypertrophied hearts translates into attenuation of cardiac dysfunction in hypertrophied hearts. Male Wistar rats (n 33) at 8 weeks of age were sham-operated or subjected to abdominal aortic stenosis to produce pressure-overload cardiac hypertrophy. Starting 3 weeks post-operatively to follow initiation of hypertrophy, rats were fed a diet containing 10 % olive oil (control) or 5 % fish oil (ROPUFA® 30 (17 % EPA, 10 % DHA))+5 % olive oil (FO diet). At 15 weeks post-operatively, ventricular haemodynamics and oxygen consumption were evaluated in the blood-perfused, isolated working heart. Resting and maximally stimulated cardiac output and external work were >60 % depressed in hypertrophied control hearts but this was prevented by FO feeding, without attenuating hypertrophy. Cardiac energy efficiency was lower in hypertrophy, but greater in FO hearts for any given cardiac mass. Coronary blood flow, restricted in hypertrophied control hearts, increased with increasing work in hypertrophied FO hearts, revealing a significant coronary vasodilator reserve. Pronounced cardiac dysfunction in hypertrophied hearts across low and high workloads, indicative of heart failure, was attenuated by FO feeding in association with membrane incorporation of n-3 PUFA, principally DHA. Dietary fish oil may offer a new approach to balancing the high oxygen demand and haemodynamic requirements of the failing hypertrophied heart independently of attenuating hypertrophy.

Investigating the Impact of Dragon Fruit Peel Waste on Starch Digestibility, Pasting, and Thermal Properties of Flours Used in Asia.

As a by-product of dragon fruit consumption, dragon fruit peel (DFP) was developed into powder as a natural ingredient. Nevertheless, the effect of DFP on the physicochemical properties of flours used in Asian food processing and cooking remains unknown. In this study, starch digestibility, thermal, pasting, and physicochemical properties of DFP and flours (potato, rice, glutinous rice, and wheat) were characterized. It was found that DFP contained 65.2% dietary fiber together with phenolic compounds, betacyanins, and antioxidant activity. The results demonstrated that DFP (from 125 to 500 mg) reduced starch digestibility of flours, rapidly digestible starch, and slowly digestible starch, along with an increased proportion of undigested starch. A marked increase in phenolic compounds, betacyanins, and antioxidant activity occurred when DFP and flour were incubated for 180 min under simulated gastrointestinal digestion. The results indicate that bioactive compounds in DFP were highly bioaccessible and remained intact after digestion. Moreover, DFP exerted a significantly lower gelatinization enthalpy of flours with increasing peak viscosity and setback with decreasing pasting temperature. FTIR confirmed the decreased ratio at 1047/1022 cm-1, indicating the disruption of short-range orders of starch and DFP. These findings would expand the scope of DFP food applications and provide a knowledge basis for developing DFP flour-based products.

Positive outcomes of oil palm phenolics on degenerative diseases in animal models.

It is well established that plant phenolics elicit various biological activities, with positive effects on health. Palm oil production results in large volumes of aqueous by-products containing phenolics. In the present study, we describe the effects of oil palm phenolics (OPP) on several degenerative conditions using various animal models. OPP reduced blood pressure in a NO-deficient rat model, protected against ischaemia-induced cardiac arrhythmia in rats and reduced plaque formation in rabbits fed an atherogenic diet. In Nile rats, a spontaneous model of the metabolic syndrome and type 2 diabetes, OPP protected against multiple aspects of the syndrome and diabetes progression. In tumour-inoculated mice, OPP protected against cancer progression. Microarray studies on the tumours showed differential transcriptome profiles that suggest anti-tumour molecular mechanisms involved in OPP action. Thus, initial studies suggest that OPP may have potential against several chronic disease outcomes in mammals.

Oil palm vegetation liquor: a new source of phenolic bioactives.

Waste from agricultural products represents a disposal liability, which needs to be addressed. Palm oil is the most widely traded edible oil globally, and its production generates 85 million tons of aqueous by-products annually. This aqueous stream is rich in phenolic antioxidants, which were investigated for their composition and potential in vitro biological activity. We have identified three isomers of caffeoylshikimic acid as major components of oil palm phenolics (OPP). The 2,2-diphenyl-1-picrylhydrazyl assay confirmed potent free radical scavenging activity. To test for possible cardioprotective effects of OPP, we carried out in vitro LDL oxidation studies as well as ex vivo aortic ring and mesenteric vascular bed relaxation measurements. We found that OPP inhibited the Cu-mediated oxidation of human LDL. OPP also promoted vascular relaxation in both isolated aortic rings and perfused mesenteric vascular beds pre-contracted with noradrenaline. To rule out developmental toxicity, we performed teratological studies on rats up to the third generation and did not find any congenital anomalies. Thus, these initial studies suggest that OPP is safe and may have a protective role against free radical damage, LDL oxidation and its attendant negative effects, as well as vascular constriction in mitigating atherosclerosis. Oil palm vegetation liquor thus represents a new source of phenolic bioactives.

Palmitic Acid, but Not Lauric Acid, Induces Metabolic Inflammation, Mitochondrial Fragmentation, and a Drop in Mitochondrial Membrane Potential in Human Primary Myotubes.

The chain length of saturated fatty acids may dictate their impact on inflammation and mitochondrial dysfunction, two pivotal players in the pathogenesis of insulin resistance. However, these paradigms have only been investigated in animal models and cell lines so far. Thus, the aim of this study was to compare the effect of palmitic (PA) (16:0) and lauric (LA) (12:0) acid on human primary myotubes mitochondrial health and metabolic inflammation. Human primary myotubes were challenged with either PA or LA (500 µM). After 24 h, the expression of interleukin 6 (IL-6) was assessed by quantitative polymerase chain reaction (PCR), whereas Western blot was used to quantify the abundance of the inhibitor of nuclear factor κB (IκBα), electron transport chain complex proteins and mitofusin-2 (MFN-2). Mitochondrial membrane potential and dynamics were evaluated using tetraethylbenzimidazolylcarbocyanine iodide (JC-1) and immunocytochemistry, respectively. PA, contrarily to LA, triggered an inflammatory response marked by the upregulation of IL-6 mRNA (11-fold; P < 0.01) and a decrease in IκBα (32%; P < 0.05). Furthermore, whereas PA and LA did not differently modulate the levels of mitochondrial electron transport chain complex proteins, PA induced mitochondrial fragmentation (37%; P < 0.001), decreased MFN-2 (38%; P < 0.05), and caused a drop in mitochondrial membrane potential (11%; P < 0.01) compared to control, with this effect being absent in LA-treated cells. Thus, LA, as opposed to PA, did not trigger pathogenetic mechanisms proposed to be linked with insulin resistance and therefore represents a healthier saturated fatty acid choice to potentially preserve skeletal muscle metabolic health.

Eucaloric diets enriched in palm olein, cocoa butter, and soybean oil did not differentially affect liver fat concentration in healthy participants: a 16-week randomized controlled trial.

BACKGROUND: Effects of dietary fat quality on liver fat remain to be elucidated. Inconsistent evidence may be influenced by fatty acid saturation, chain-length, and regio-specificity within triacylglycerol (TAG) molecules. OBJECTIVES: We aimed to compare eucaloric diets enriched in palm olein (POo), cocoa butter (COB), and soybean oil (SBO) on liver fat concentration in healthy participants. Secondary outcomes included visceral (VAT) and abdominal subcutaneous (aSCAT) adipose tissue, plus other obesity and cardiometabolic health outcomes. METHODS: Eighty-three healthy participants (20-45 y, BMI 18.5-27.5 kg/m2) commenced and 64 completed a 16-wk randomized parallel intervention, preceded by a 2-wk run-in. Participants consumed identical eucaloric background diets differing in test fats [contributing 20% total energy intake (%E)], providing 33%E total fat with the following ratios for PUFAs/SFAs/MUFAs: POo, 4.2/13.5/15%E; SBO, 14.4/8.8/9.4%E; COB, 2.3/19.5/11%E. Liver fat and abdominal adiposity were measured at weeks 0 and 16 using 1H-magnetic resonance spectroscopy/imaging; all other outcomes were measured at 0, 4, 8, 12, and 16 wk. RESULTS: Fat quality did not affect liver fat concentration, VAT, aSCAT, obesity indexes, blood pressure, liver enzymes, leptin, or fasting glucose. Body fat mass decreased with SBO and COB compared with POo. SBO decreased serum total cholesterol (TC), LDL cholesterol, and TC:HDL cholesterol relative to POo [estimated marginal mean (95% CI) differences: -0.57 (-0.94, -0.20) mmol/L; -0.37 (-0.68, -0.07) mmol/L; and -0.42 (-0.73, -0.11) mmol/L, respectively]. No diet differences were observed on HDL cholesterol, TAG, apoA1, apoB, apoB:apoA1, or fecal free fatty acids (FFAs), except for lower FFA pentadecanoic acid (15:0) with COB than with SBO and POo. CONCLUSIONS: In healthy adults, when consumed as part of eucaloric typical Australian diets, 3 different dietary fat sources did not differentially affect liver fat concentration and amounts of adipose tissue. Effects on serum lipids were inconsistent across lipid profiles. The findings must be confirmed in metabolically impaired individuals before recommendations can be made.

Fatty acid regio-specificity of triacylglycerol molecules may affect plasma lipid responses to dietary fats-a randomised controlled cross-over trial.

BACKGROUND/OBJECTIVES: Hypercholesterolaemic effects of saturated fatty acids (SFA) may be influenced not only by the chain length, but also by their specific location within the triacylglycerol (TAG) molecule. We examined the hypothesis that dietary fats rich in SFA, but containing mostly unsaturated fatty acids in the sn-2 position with most SFA in sn-1 and -3 (palm olein [PO] and cocoa butter [CB]) will have similar serum lipid outcomes to unsaturated olive oil (OO). SUBJECTS/METHODS: Thirty-eight participants (20-40 yr, 18.5- ≤ 27.5 kg/m2) completed a 4-week randomised 3 × 3 crossover feeding intervention, preceded by 2-week run-in and separated by 2-week washout periods. Background diet contained 35 percentage of total energy (%E) fat, 18%E protein, 48%E carbohydrates, differing in test fats only (palm olein (PO), CB, OO; 20%E). Total cholesterol (TC)/high density lipoprotein cholesterol (HDL-C) ratio and related variables; TC, HDL-C, low density lipoprotein cholesterol (LDL-C), TAG, apoA1, ApoB, ApoA1 (apolipoprotein A1)/ApoB (apolipoprotein B), lipoprotein (a) (Lp(a)), NEFA, LDL sub-fractions, were assessed pre- and post-intervention. Data were analysed using mixed effects longitudinal models with a P-value < 0.05 considered significant. RESULTS: Changes in plasma fatty acids (P < 0.05) confirmed compliance; C18:1 increased with OO compared to PO and CB; C16:0 decreased with OO and C18:0 increased following CB. No differences were seen for TC/HDL-C (mean [95%CI] change for PO, 0.08[0.00, 0.15] mmol/L; CB, 0.06 [-0.05, 0.16] mmol/L; and OO, -0.01 [-0.15, 0.13] mmol/L; P = 0.53] or any other parameter including LDL sub-fractions. OO decreased IDL-A compared to PO (-2.2 [-4.31, -0.21] mg/dL, P = 0.03). CONCLUSION: In healthy young participants, plasma lipid responses to PO and CB, enriched in SFA but having primarily unsaturated fatty acid in the sn-2 position of TAG, did not differ from OO.

Consumption of an Oil Palm Fruit Extract Promotes Large Bowel Health in Rats.

Oil palm fruit is widely used for edible oils, but the health benefits of other components are relatively unknown. We examined if consuming a polyphenol-rich extract of the fruit, from a vegetation by-product of oil processing, which also contains fibre, has gastro-intestinal benefits in rats on a Western-type diet (WD). The oil palm preparation (OPP) was added to food (OPP-F) or drinking water (OPP-D) to provide 50 mg of gallic acid equivalents (GAE)/d and compared to effects of high amylose maize starch (HAMS; 30%) in the diet or green tea extract (GT; 50 mg GAE/d) in drinking water over 4 wk. OPP treatments induced some significant effects (P < 0.05) compared to WD. OPP-D increased caecal digesta mass, caecal digesta concentrations of total SCFA, acetate and propionate (OPP-F increased caecal butyrate concentration), the numbers of mucus-producing goblet cells per colonic crypt, and caecal digesta abundance of some bacteria which may provide benefit to the host (Faecalibacterium prausnitzii, Akkermansia muciniphila and Ruminococcus gnavus). HAMS induced similar effects but with greater potency and had a broader impact on microbe populations, whereas GT had minimal impacts. These results suggest dietary OPP may benefit the large bowel.

Radioligand binding assays: application of [(125)I]angiotensin II receptor binding.

Angiotensin II (AngII) is an octapeptide hormone with a key role in blood pressure regulation. AngII increases blood pressure by stimulating G protein-coupled receptors in vascular smooth muscle. AngII receptors are therefore an important target in patients with high blood pressure. Strategies to lower high blood pressure (hypertension) include the use of drugs that compete for AngII at the angiotensin II Type 1 receptors (ATR) using ATR antagonists (e.g., irbesartan, valsartan, and losartan). This chapter will demonstrate the subtype specificity of ATR binding and we discuss some of the key experiments that are necessary in optimizing some of the parameters for GPCR screening. The latter protocols include saturation binding to determine K (d) and B (max), as well as competition/inhibition experiments to determine the IC(50) of binding. For these experiments we have used rat liver membranes which express ATR (type 1a) in relatively abundant amounts. Additionally, rat liver membrane preparations can be easily prepared in "bulk," frozen away for extended periods (up to 1 year) and used when necessary with no loss of receptor binding activity using the radiolabeled angiotensin II analogue, [(125)I][Sar(1),I le(8)]AngII.

Site specific delivery of microencapsulated fish oil to the gastrointestinal tract of the rat.

The aim of this study was to design food grade matrices to deliver microencapsulated fish oil to the large bowel of the rat where the potential exists to retard inflammation and cancer development. Digestion in simulated gastric fluid and intestinal fluid demonstrated that only 4-6% of oil was released from the following dried emulsion formulations: 50% fish oil encapsulated in heated casein-glucose-dried glucose syrup (1:1:1) (Cas-Glu-DGS-50); 25% fish oil in casein-modified resistant starch (Hylon VII) (1:1) (Cas-Hylon-25); or 25% fish oil in Cas-Glu-Hylon (1:1:1) (Cas-Glu-Hylon-25). A short-term gavage study (0-12 h) with fish oil and Cas-Glu-DGS-50 demonstrated the appearance of fish oil long chain (LC) n-3 polyunsaturated fatty acids (PUFA) into the plasma indicating specific small intestinal absorption with little LC n-3 PUFA reaching the large bowel. In a 2-week-long term, daily gavage study, the bioavailability of fish oil and fish oil in Cas-Glu-DGS-50 or Cas-Hylon-25 demonstrated that fish oil and Cas-Glu-DGS-50 LC n-3 PUFA were incorporated into the tissue of the small intestine and colon, whereas Cas-Hylon-25 was resistant to degradation in the small intestine. The use of modified Hylon VII for targeted colonic delivery was confirmed in the final short-term gavage study (0-14 h) using Cas-Glu-Hylon-25 with [(14)C]-trilinolenin as a marker incorporated into the microcapsules, where up to 60% of the labeled oil reached the large bowel. Depending on the microencapsulating matrix employed, fish oil can be delivered selectively to the small intestine or to a high degree to the large bowel.