Deleterious Effects of Lard-enriched Diet on Tissues Fatty Acids Composition and Hypothalamic Insulin Actions

Altered tissue fatty acid (FA) composition may affect mechanisms involved in the control of energy homeostasis, including central insulin actions. In rats fed either standard chow or a lard-enriched chow (high in saturated/low in polyunsaturated FA, HS-LP) for eight weeks, we examined the FA composition of blood, hypothalamus, liver, and retroperitoneal, epididymal and mesenteric adipose tissues. Insulin-induced hypophagia and hypothalamic signaling were evaluated after intracerebroventricular insulin injection. HS-LP feeding increased saturated FA content in adipose tissues and serum while it decreased polyunsaturated FA content of adipose tissues, serum, and liver. Hypothalamic C20:5n-3 and C20:3n-6 contents increased while monounsaturated FA content decreased. HS-LP rats showed hyperglycemia, impaired insulin-induced hypophagia and hypothalamic insulin signaling. The results showed that, upon HS-LP feeding, peripheral tissues underwent potentially deleterious alterations in their FA composition, whist the hypothalamus was relatively preserved. However, hypothalamic insulin signaling and hypophagia were drastically impaired. These findings suggest that impairment of hypothalamic insulin actions by HS-LP feeding was not related to tissue FA composition.

Long Chain Saturated Fatty Acids Increase Haptoglobin Gene Expression in C57BL/6J Mice Adipose Tissue and 3T3-L1 Cells

Background Dietary lipids are directly related to the composition of adipose tissue, aetiology of obesity and arousal of obesity-related pathologies, like chronic inflammation states. Haptoglobin is an acute phase protein secreted by the liver and white adipose tissue, and its blood levels vary according to the volume of fat in the body. Aim of the study To investigate the effect of diets enriched with large amounts of dietary fats, which differ in their fatty acid composition, on the haptoglobin gene expression by visceral and subcutaneous adipose tissue of mice fed for 2 days or 8 weeks. 3T3-L1 cells were treated with fatty acids that are found in those types of dietary fats. Methods Mice were treated acutely (for 2 days) or chronically (for 8 weeks) with diets enriched with soybean oil, fish oil, coconut oil or lard. 3T3-L1 cells were treated with six different fatty acids. Haptoglobin gene expression was quantified by northern blotting. Results Both chronic and acute treatment with lard, which is rich in long chain saturated fatty acids, increased the haptoglobin mRNA expression in the retroperitoneal and epidydimal white adipose tissues. Chronic treatment with coconut oil, which is rich in medium chain saturated fatty acids, increased the haptoglobin expression in the epidydimal and subcutaneous depots. In 3T3-L1, palmitic acid increased the haptoglobin gene expression. Conclusion The type of lipids in the diet can differently modulate the white adipose tissue gene expression of haptoglobin, and saturated fatty acids play a major role in promoting a pro-inflammatory environment. This response is fat pad specific and dependant on the duration of treatment.

Low- vs. high-glycemic load diets: effects on postprandial plasma free fatty acids

Thesis (Master's)--University of Washington, 2016-06

New N-acylamino acids and derivatives from renewable fatty acids: gelation of hydrocarbons and thermal properties

This work reports the synthesis of new fatty N-acylamino acids and N-acylamino esters from the C16:0, C18:0, C18:1, and C18:1(OH) fatty acid families and demonstrates the activity of these compounds as organogel agents. Compounds were heated and dissolved in various solvents (n-hexane, toluene, and gasoline). Only saturated C16:0 and C18:0 derived from alanine were able to form gels in toluene, and saturated C16:0 derived from phenylalanine showed gelation in n-hexane. This is the first evidence that fatty N-acylamino esters and N-acylamino acid derivatives of l-serine and fatty acids C16:0, C18:0, and C18:1 are able to form gels with hexane. This observation confirms the importance of the hydroxyl group in the segment derivative of l-serine in forming good gels.

EFFECT OF INTERMITTENT FRYING ON FATTY ACIDS, VITAMIN E, LIPID OXIDATION AND ACRYLAMIDE IN OILS AND PLANTAIN CHIPS COLLECTED FROM SMALL- SCALE PRODUCERS IN CAMEROON

Deep-fat frying is susceptible to induce the formation of undesirable products as lipid oxidation products and acrylamide in fried foods. Plantain chips produced by small-scale producers are sold to consumers without any control. The objective of this study was to evaluate the quality of plantain chips from local producers in relation to production process parameters and oils, and to identify the limiting factors for the production of acrylamide in plantain chips. Samples of frying oils and plantain chips prepared with either palm olein or soybean oil were collected from 10 producers in Yaoundé. Quality parameters determined in this study were: fatty acid composition of the oils, determined by gas chromatography (GC) of free acid methyl ester; trans fatty acids, determined by Fourier transform infra-red spectroscopy; Tocopherols and tocotrienols as markers of nutritional quality were analyzed by High Performance Liquid Chromatography in isocratic mode. Free fatty acids and acylglycerols as markers of lipid hydrolysis were analyzed by GC of trimethylsilyl derivatives of glycerides. Conjugated dienes, Anisidine value and viscosity as markers of lipid oxidation and thermal decomposition of the oils; acrylamide which is formed through Maillard reaction and identified as a toxic compound in various fried products. Asparagine content of the raw fresh plantain powder was also determined. Fatty acid composition of palm oleins was stable within a day of intermittent frying. In soybean oils, about 57% and 62.5% of linoleic and linolenic acids were lost but trans fatty acids were not detected. Soybean oils were partly hydrolysed leading to the formation of free fatty acids, monoacylglycerols and diacylglycerols. In both oils, tocopherols and tocotrienols contents decreased significantly by about 50%. Anisidine value (AV) and polymers contents increased slightly in fried palm oleins while conjugated hydroperoxides, AV and polymers greatly increased in soybean oils. Acrylamide was not detected in the chips. This is explained by the absence of asparagine in the raw plantains, the other acrylamide precursors being present. This study shows that the plantain chips prepared at the small-scale level in Yaounde with palm olein are of good quality regarding oxidation and hydrolysis parameters and the absence of acrylamide. In contrast, oxidation developed with soybean oil whose usage for frying should be questioned. Considering that asparagine is the limiting factor for the formation of acrylamide in plantain chips, its content depending on several factors such as production parameters and maturity stage should be explored.

Enhancing bioactive fatty acids of the meat from lambs reared in intensive systems through nutritional modulation

Tese de Doutoramento em Ciências Veterinárias, especialidade de Produção Animal

Quality of polyunsaturated fatty acids in Nile tilapias (Oreochromis niloticus) fed with vitamin E supplementation

Freshwater fish are an important source of protein, but they also contain other highly nutritive components such as fats. Polyunsaturated fatty acids (PUFAs) are essential for normal growth, development and reproduction of vertebrates. The antioxidant role of vitamin E in cell membranes prevents fatty acid and cholesterol oxidation, thereby promoting PUFA and subcellular particle stabilization. The effects of vitamin E supplementation on the quality of Nile tilapia (Oreochromis niloticus) carcass were investigated. The experiments were carried out in an experimental laboratory over 106 d. After sex reversal, 400 early juvenile O. niloticus were tested in a completely randomized experiment with 5 treatments (4 repetitions each), consisting of vitamin E monophosphate supplementation at 0, 50, 100, 150 or 200 mg/kg of a base diet. Treatment diets contained equal amounts of protein and energy. Tilapias supplemented with vitamin E contained arachidonic acid (20:4 omega-6; AA) which participates in inflammatory response. Nile tilapia carcasses that received vitamin E at 100 and 150 mg/kg diet had improved carcass quality by increasing the PUFA:SFA ratio and had the highest levels of polyunsaturated fatty acids from the omega-3 (linolenic acid; 18:3 omega-3) and omega-6 (linoleic acid; 18:2 omega-6) series. (C) 2012 Elsevier Ltd. All rights reserved.

Forms of n-3 (ALA, C18:3n-3 or DHA, C22:6n-3) fatty acids affect carcass yield, blood lipids, muscle n-3 fatty acids and liver gene expression in lambs

The effects of supplementing diets with n-3 alpha-linolenic acid (ALA) and docosahexaenoic acid (DHA) on plasma metabolites, carcass yield, muscle n-3 fatty acids and liver messenger RNA (mRNA) in lambs were investigated. Lambs (n = 120) were stratified to 12 groups based on body weight (35 ± 3.1 kg), and within groups randomly allocated to four dietary treatments: basal diet (BAS), BAS with 10.7 % flaxseed supplement (Flax), BAS with 1.8 % algae supplement (DHA), BAS with Flax and DHA (FlaxDHA). Lambs were fed for 56 days. Blood samples were collected on day 0 and day 56, and plasma analysed for insulin and lipids. Lambs were slaughtered, and carcass traits measured. At 30 min and 24 h, liver and muscle samples, respectively, were collected for determination of mRNA (FADS1, FADS2, CPT1A, ACOX1) and fatty acid composition. Lambs fed Flax had higher plasma triacylglycerol, body weight, body fat and carcass yield compared with the BAS group (P < 0.001). DHA supplementation increased carcass yield and muscle DHA while lowering plasma insulin compared with the BAS diet (P < 0.01). Flax treatment increased (P < 0.001) muscle ALA concentration, while DHA treatment increased (P < 0.001) muscle DHA concentration. Liver mRNA FADS2 was higher and CPT1A lower in the DHA group (P < 0.05). The FlaxDHA diet had additive effects, including higher FADS1 and ACOX1 mRNA than for the Flax or DHA diet. In summary, supplementation with ALA or DHA modulated plasma metabolites, muscle DHA, body fat and liver gene expression differently.

Hydroxyoctadecadienoic acids: Oxidised derivatives of linoleic acid and their role in inflammation associated with metabolic syndrome and cancer

Linoleic acid (LA) is a major constituent of low-density lipoproteins. An essential fatty acid, LA is a polyunsaturated fatty acid, which is oxidised by endogenous enzymes and reactive oxygen species in the circulation. Increased levels of low-density lipoproteins coupled with oxidative stress and lack of antioxidants drive the oxidative processes. This results in synthesis of a range of oxidised derivatives, which play a vital role in regulation of inflammatory processes. The derivatives of LA include, hydroxyoctadecadienoic acids, oxo-​octadecadienoic acids, epoxy octadecadecenoic acid and epoxy-keto-octadecenoic acids. In this review, we examine the role of LA derivatives and their actions on regulation of inflammation relevant to metabolic processes associated with atherogenesis and cancer. The processes affected by LA derivatives include, alteration of airway smooth muscles and vascular wall, affecting sensitivity to pain, and regulating endogenous steroid hormones associated with metabolic syndrome. LA derivatives alter cell adhesion molecules, this initial step, is pivotal in regulating inflammatory processes involving transcription factor peroxisome proliferator-activated receptor pathways, thus, leading to alteration of metabolic processes. The derivatives are known to elicit pleiotropic effects that are either beneficial or detrimental in nature hence making it difficult to determine the exact role of these derivatives in the progress of an assumed target disorder. The key may lie in understanding the role of these derivatives at various stages of development of a disorder. Novel pharmacological approaches in altering the synthesis or introduction of synthesised LA derivatives could possibly help drive processes that could regulate inflammation in a beneficial manner. Chemical Compounds: Linoleic acid (PubChem CID: 5280450), 9- hydroxyoctadecadienoic acid (PubChem CID: 5312830), 13- hydroxyoctadecadienoic acid (PubChem CID: 6443013), 9-oxo-​octadecadienoic acid (PubChem CID: 3083831), 13-oxo-​octadecadienoic acid (PubChem CID: 4163990), 9,10-epoxy-12-octadecenoate (PubChem CID: 5283018), 12,13-epoxy-9-keto-10- trans -octadecenoic acid (PubChem CID: 53394018), Pioglitazone (PubChem CID: 4829).

Eicosapentaenoic acid, arachidonic acid and eicosanoid metabolism in juvenile barramundi Lates calcarifer

A two part experiment was conducted to assess the response of barramundi (Lates calcarifer; initial weight = 10.3 ± 0.03 g; mean ± S.D.) fed one of five diets with varying eicosapentaenoic acid (diets 1, 5, 10, 15 and 20 g/kg) or one of four diets with varying arachidonic acid (1, 6, 12, 18 g/kg) against a fish oil control diet. After 6 weeks of feeding, the addition of EPA or ARA did not impact on growth performance or feed utilisation. Analysis of the whole body fatty acids showed that these reflected those of the diets. The ARA retention demonstrated an inversely related curvilinear response to either EPA or ARA. The calculated marginal utilisation efficiencies of EPA and ARA were high (62.1 and 91.9 % respectively) and a dietary ARA requirement was defined (0.012 g/kg(0.796)/day). The partial cDNA sequences of genes regulating eicosanoid biosynthesis were identified in barramundi tissues, namely cyclooxygenase 1 (Lc COX1a, Lc COX1b), cyclooxygenase 2 (Lc COX2) and lipoxygenase (Lc ALOX-5). Both Lc COX2 and Lc ALOX-5 expression in the liver tissue were elevated in response to increasing dietary ARA, meanwhile expression levels of Lc COX2 and the mitochondrial fatty acid oxidation gene carnitine palmitoyltransferase 1 (Lc CPT1a) were elevated in the kidney. A low level of EPA increased the expression of Lc COX1b in the liver. Consideration should be given to the EPA to ARA balance for juvenile barramundi in light of nutritionally inducible nature of the cyclooxygenase and lipoxygenase enzymes.

Increased erythrocyte eicosapentaenoic acid and docosahexaenoic acid are associated with improved attention and behavior in children with ADHD in a randomized controlled three-way crossover trial

OBJECTIVE: To investigate effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on attention, literacy, and behavior in children with ADHD.

METHOD: Ninety children were randomized to consume supplements high in EPA, DHA, or linoleic acid (control) for 4 months each in a crossover design. Erythrocyte fatty acids, attention, cognition, literacy, and Conners' Parent Rating Scales (CPRS) were measured at 0, 4, 8, 12 months.

RESULTS: Fifty-three children completed the treatment. Outcome measures showed no significant differences between the three treatments. However, in children with blood samples (n = 76-46), increased erythrocyte EPA + DHA was associated with improved spelling (r = .365, p < .001) and attention (r = -.540, p < .001) and reduced oppositional behavior (r = -.301, p < .003), hyperactivity (r = -.310, p < .001), cognitive problems (r = -.326, p < .001), Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) hyperactivity (r = -.270, p = .002) and DSM-IV inattention (r = -.343, p < .001).

CONCLUSION: Increasing erythrocyte DHA and EPA via dietary supplementation may improve behavior, attention, and literacy in children with ADHD.

Divergent shifts in lipid mediator profile following supplementation with n-3 docosapentaenoic acid and eicosapentaenoic acid

In contrast to the well-characterized effects of specialized proresolving lipid mediators (SPMs) derived from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), little is known about the metabolic fate of the intermediary long-chain (LC) n-3 polyunsaturated fatty acid (PUFA) docosapentaenoic acid (DPA). In this double blind crossover study, shifts in circulating levels of n-3 and n-6 PUFA-derived bioactive lipid mediators were quantified by an unbiased liquid chromatography-tandem mass spectrometry lipidomic approach. Plasma was obtained from human subjects before and after 7 d of supplementation with pure n-3 DPA, n-3 EPA or placebo (olive oil). DPA supplementation increased the SPM resolvin D5n-3DPA (RvD5n-3DPA) and maresin (MaR)-1, the DHA vicinal diol 19,20-dihydroxy-DPA and n-6 PUFA derived 15-keto-PG E2 (15-keto-PGE2). EPA supplementation had no effect on any plasma DPA or DHA derived mediators, but markedly elevated monohydroxy-eicosapentaenoic acids (HEPEs), including the e-series resolvin (RvE) precursor 18-HEPE; effects not observed with DPA supplementation. These data show that dietary n-3 DPA and EPA have highly divergent effects on human lipid mediator profile, with no overlap in PUFA metabolites formed. The recently uncovered biologic activity of n-3 DPA docosanoids and their marked modulation by dietary DPA intake reveals a unique and specific role of n-3 DPA in human physiology.-Markworth, J. F., Kaur, G., Miller, E. G., Larsen, A. E., Sinclair, A. J., Maddipati, K. R., Cameron-Smith, D. Divergent shifts in lipid mediator profile following supplementation with n-3 docosapentaenoic acid and eicosapentaenoic acid.

Apicoplast-localized lysophosphatidic acid precursor assembly is required for bulk phospholipid synthesis in toxoplasma gondii and relies on an algal/plant-like glycerol 3-phosphate acyltransferase

Most apicomplexan parasites possess a non-photosynthetic plastid (the apicoplast), which harbors enzymes for a number of metabolic pathways, including a prokaryotic type II fatty acid synthesis (FASII) pathway. In Toxoplasma gondii, the causative agent of toxoplasmosis, the FASII pathway is essential for parasite growth and infectivity. However, little is known about the fate of fatty acids synthesized by FASII. In this study, we have investigated the function of a plant-like glycerol 3-phosphate acyltransferase (TgATS1) that localizes to the T. gondii apicoplast. Knock-down of TgATS1 resulted in significantly reduced incorporation of FASII-synthesized fatty acids into phosphatidic acid and downstream phospholipids and a severe defect in intracellular parasite replication and survival. Lipidomic analysis demonstrated that lipid precursors are made in, and exported from, the apicoplast for de novo biosynthesis of bulk phospholipids. This study reveals that the apicoplast-located FASII and ATS1, which are primarily used to generate plastid galactolipids in plants and algae, instead generate bulk phospholipids for membrane biogenesis in T. gondii.

Real-time quartz crystal microbalance monitoring of free docosahexaenoic acid interactions with supported lipid bilayers.

Docosahexaenoic acid (DHA) is the most abundant polyunsaturated omega-3 fatty acid found in mammalian neuronal cell membranes. Although DHA is known to be important for neuronal cell survival, little is know about how DHA interacts with phospholipid bilayers. This study presents a detailed quartz crystal microbalance with dissipation monitoring (QCM-D) analysis of free DHA interactions with individual and mixed phospholipid supported lipid bilayers (SLB). DHA incorporation and subsequent changes to the SLBs viscoelastic properties were observed to be concentration-dependent, influenced by the phospholipid species, the headgroup charge, and the presence or absence of calcium ions. It was observed that 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) SLBs incorporated the greatest amount of DHA concentration, whereas the presence of phospholipids, phosphatidylserine (PS), and phosphatidylinositol (PI) in a POPC SLB significantly reduced DHA incorporation and changed the SLBs physicochemical properties. These observations are hypothesized to be due to a substitution event occurring between DHA and phospholipid species. PS domain formation in POPC/PS 8:2 SLBs was observed in the presence of calcium ions, which favored DHA incorporation to a similar level as for a POPC only SLB. The changes in SLB thickness observed with different DHA concentrations are also presented. This work contributes to an understanding of the physical changes induced in a lipid bilayer as a consequence of its exposure to different DHA concentrations (from 50 to 200 μM). The capacity of DHA to influence the physical properties of SLBs indicates the potential for dietary DHA supplementation to cause changes in cellular membranes in vivo, with subsequent physiological consequences for cell function.

Effects of different forms of docosahexaenoic acid supplementations on human neuronal cells

My study showed that Docosahexaenoic Acid (DHA), a major dietary omega-3 polyunsaturated fatty acid, inhibited cell death and promoted electro-physiological activity in cultured neuronal cells. The free fatty acid form was more effective than DHA-phospholipids and DHA-nanoliposomes. This study provides insights into the beneficial effects of dietary omega-3 fatty acids.