A new integrated strategy for high purity pinolenic acid production from Pinus koraiensis Sieb. et Zucc seed oil and evaluation of its hypolipidemic activity in vivo.

Pinolenic acid is a polyunsaturated fatty acid present only in Pinus koraiensis Sieb. et Zucc seed oil. In order to solve the structural instability problem of polyunsaturated fatty acids, pinolenic acid of P. koraiensis seed oil was effectively isolated and purified by the integrated strategy of ethyl esterification followed by urea inclusion for the first time. Under the optimal conditions after the Box-Benhnken Design experimental, ethyl pinolenate with high purity 94.95% could be obtained, and the average content of PNAEE can still reach 86.18%. Then ethyl pinolenate was characterized by Gas chromatography-mass spectrometry, Fourier transform infrared, and Nuclear magnetic resonance spectra, results showed that ethyl pinolenate was successfully prepared. In addition, the hypolipidemic activity of ethyl pinolenate had been tested in vivo and showed that ethyl pinolenate had obvious hypolipidemic activity. The new strategy for high purity ethyl pinolenate production from P. koraiensis seed oil possesses great potential in food healthy field in the future.

The Beneficial Effects of Pine Nuts and Its Major Fatty Acid, Pinolenic Acid, on Inflammation and Metabolic Perturbations in Inflammatory Disorders.

Inflammatory disorders such as atherosclerosis, diabetes and rheumatoid arthritis are regulated by cytokines and other inflammatory mediators. Current treatments for these conditions are associated with significant side effects and do not completely suppress inflammation. The benefits of diet, especially the role of specific components, are poorly understood. Polyunsaturated fatty acids (PUFAs) have several beneficial health effects. The majority of studies on PUFAs have been on omega-3 fatty acids. This review will focus on a less studied fatty acid, pinolenic acid (PNLA) from pine nuts, which typically constitutes up to 20% of its total fatty acids. PNLA is emerging as a dietary PUFA and a promising supplement in the prevention of inflammatory disorders or as an alternative therapy. Some studies have shown the health implications of pine nuts oil (PNO) and PNLA in weight reduction, lipid-lowering and anti-diabetic actions as well as in suppression of cell invasiveness and motility in cancer. However, few reviews have specifically focused on the biological and anti-inflammatory effects of PNLA. Furthermore, in recent bioinformatic studies on human samples, the expression of many mRNAs and microRNAs was regulated by PNLA indicating potential transcriptional and post-transcriptional regulation of inflammatory and metabolic processes. The aim of this review is to summarize, highlight, and evaluate research findings on PNO and PNLA in relation to potential anti-inflammatory benefits and beneficial metabolic changes. In this context, the focus of the review is on the potential actions of PNLA on inflammation along with modulation of lipid metabolism and oxidative stress based on data from both in vitro and in vivo experiments, and human findings, including gene expression analysis.

Pomegranate Seed Oil as a Source of Conjugated Linolenic Acid (CLnA) Has No Effect on Atherosclerosis Development but Improves Lipid Profile and Affects the Expression of Lipid Metabolism Genes in apoE/LDLR-/- Mice.

The aim of this study was to evaluate the anti-atherosclerotic effect of pomegranate seed oil as a source of conjugated linolenic acid (CLnA) (cis-9,trans-11,cis-13; punicic acid) compared to linolenic acid (LnA) and conjugated linoleic acid (CLA) (cis-9,trans-11) in apoE/LDLR-/- mice. In the LONG experiment, 10-week old mice were fed for the 18 weeks. In the SHORT experiment, 18-week old mice were fed for the 10 weeks. Diets were supplied with seed oils equivalent to an amount of 0.5% of studied fatty acids. In the SHORT experiment, plasma TCh and LDL+VLDL cholesterol levels were significantly decreased in animals fed CLnA and CLA compared to the Control. The expression of PPARα in liver was four-fold increased in CLnA group in the SHORT experiment, and as a consequence the expression of its target gene ACO was three-fold increased, whereas the liver's expression of SREBP-1 and FAS were decreased in CLnA mice only in the LONG experiment. Punicic acid and CLA isomers were determined in the adipose tissue and liver in animals receiving pomegranate seed oil. In both experiments, there were no effects on the area of atherosclerotic plaque in aortic roots. However, in the SHORT experiment, the area of atherosclerosis in the entire aorta in the CLA group compared to CLnA and LnA was significantly decreased. In conclusion, CLnA improved the lipid profile and affected the lipid metabolism gene expression, but did not have the impact on the development of atherosclerotic plaque in apoE/LDLR-/- mice.

Lipophilic Compounds and Antibacterial Activity of Opuntia ficus-indica Root Extracts from Algeria.

The chemical composition, investigated by gas chromatography-mass spectrometry, and antibacterial activity of lipophilic extractives of three varieties of Opuntia ficus-indica roots from Algeria are reported in this paper for the first time. The results obtained revealed a total of 55 compounds, including fatty acids, sterols, monoglycerides and long chain aliphatic alcohols that were identified and quantified. ß-Sitosterol was found as the major compound of the roots of the three varieties. Furthermore, considerable amounts of essential fatty acids (ω3, ω6, and ω9) such as oleic, linoleic, and linolenic acids were also identified. The green variety was the richest among the three studied varieties. The antibacterial activity, evaluated with disc diffusion method, revealed that lipophilic extracts were effective mainly against Gram-positive Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) (19~23 mm). Gram-negative strains mainly Pseudomonas aeruginosa gave an inhibition zone of 18 mm, which is considered high antibacterial activity. The minimal inhibitory concentrations of the tested bacteria revealed interesting values against the majority of bacteria tested: 75-100 µg mL-1 for Bacillus sp., 250-350 µg/mL for the two Staphylococcus strains, 550-600 µg mL-1 for E. coli, and 750-950 µg mL-1 obtained with Pseudomonas sp. This study allows us to conclude that the lipophilic fractions of cactus roots possess interesting phytochemicals such as steroids, some fatty acids and long chain alcohols that acted as antibiotic-like compounds countering pathogenic strains.

Efficacy of Bilberry and Grape Seed Extract Supplement Interventions to Improve Glucose and Cholesterol Metabolism and Blood Pressure in Different Populations-A Systematic Review of the Literature.

Intervention with fruit extracts may lower glucose and lipid levels, as well as blood pressure. We reviewed the efficacy of bilberry and grape seed extracts to affect these outcomes across populations with varying health status, age and ethnicity, across intervention doses and durations, in 24 intervention studies with bilberry and blackcurrant (n = 4) and grape seed extract (n = 20). Bilberry and blackcurrant extract lowered average levels of glycated hemoglobin (HbA1c), at least in Chinese subjects, especially in those who were older, who were diagnosed with Type 2 Diabetes Mellitus (T2DM) and who were participating in longer-term studies. We also found good evidence that across studies and in subjects with hypercholesterolemia, T2DM or metabolic syndrome, intervention with bilberry and blackcurrant extract, and to some extent grape seed extract, significantly lowered total and low density lipoprotein (LDL) cholesterol levels after four weeks. Intervention with grape seed extract may reduce systolic and diastolic blood pressure in subjects with hypertension or metabolic syndrome. Differential responsiveness in cholesterol and blood pressure outcomes between stratified populations could not be explained by age, dose or study duration. In conclusion, bilberry and blackcurrant extract appears effective in lowering HbA1c and total and LDL cholesterol, whereas grape seed extract may lower total and LDL cholesterol, and blood pressure, in specific population groups.

Beneficial Impacts of Alpha-Eleostearic Acid from Wild Bitter Melon and Curcumin on Promotion of CDGSH Iron-Sulfur Domain 2: Therapeutic Roles in CNS Injuries and Diseases.

Neuroinflammation and abnormal mitochondrial function are related to the cause of aging, neurodegeneration, and neurotrauma. The activation of nuclear factor κB (NF-κB), exaggerating these two pathologies, underlies the pathogenesis for the aforementioned injuries and diseases in the central nervous system (CNS). CDGSH iron-sulfur domain 2 (CISD2) belongs to the human NEET protein family with the [2Fe-2S] cluster. CISD2 has been verified as an NFκB antagonist through the association with peroxisome proliferator-activated receptor-ß (PPAR-ß). This protective protein can be attenuated under circumstances of CNS injuries and diseases, thereby causing NFκB activation and exaggerating NFκB-provoked neuroinflammation and abnormal mitochondrial function. Consequently, CISD2-elevating plans of action provide pathways in the management of various disease categories. Various bioactive molecules derived from plants exert protective anti-oxidative and anti-inflammatory effects and serve as natural antioxidants, such as conjugated fatty acids and phenolic compounds. Herein, we have summarized pharmacological characters of the two phytochemicals, namely, alpha-eleostearic acid (α-ESA), an isomer of conjugated linolenic acids derived from wild bitter melon (Momordica charantia L. var. abbreviata Ser.), and curcumin, a polyphenol derived from rhizomes of Curcuma longa L. In this review, the unique function of the CISD2-elevating effect of α-ESA and curcumin are particularly emphasized, and these natural compounds are expected to serve as a potential therapeutic target for CNS injuries and diseases.

Chia oil induces browning of white adipose tissue in high-fat diet-induced obese mice.

Previous research suggests that omega-3 fatty acids from animal origin may promote the browning of subcutaneous white adipose tissue. We evaluated if supplementation with a plant oil (chia, Salvia hispanica L.) rich in alpha-linolenic fatty acid (C18:3; ω-3) would promote browning and improve glucose metabolism in animals subjected to an obesogenic diet. Swiss male mice (n = 28) were divided into 4 groups: C: control diet; H: high-fat diet; HC: animals in the H group supplemented with chia oil after reaching obesity; HCW: animals fed since weaning on a high-fat diet supplemented with chia oil. Glucose tolerance, inflammatory markers, and expression of genes and proteins involved in the browning process were examined. When supplemented since weaning, chia oil improved glucose metabolism and promoted the browning process and a healthier phenotype. Results of this study suggested that chia oil has potential to protect against the development of obesity-related diseases.

Combined effects of oleic, linoleic and linolenic acids on lactation performance and the milk fatty acid profile in lactating dairy cows.

The potential combined effects of oleic, linoleic and linolenic acids supplementation on lactation performance and the milk fatty acid (FA) profile in dairy cows have not been well investigated. Our objective was to examine the effects of supplementation with a combination of these FA as well as the effects of removing each from the combination on lactation performance and the milk FA profile in dairy cows. Eight Holstein cows (101±11 days in milk) received four intravenously infused treatments in a 4×4 Latin square design, and each period lasted for 12 days which consisted of 5 days of infusion and 7 days of recovery. The control treatment (CTL) contained 58.30, 58.17 and 39.96 g/day of C18 : 1 cis-9; C18 : 2 cis-9, cis-12; and C18 : 3 cis-9, cis-12, cis-15, respectively. The other three treatments were designated --C18 : 1 (20.68, 61.17 and 41.72 g/day of C18 : 1 cis-9; C18 : 2 cis-9, cis-12; and C18 : 3 cis-9, cis-12, cis-15, respectively), -C18 : 2 (61.49, 19.55 and 42.13 g/day of C18 : 1 cis-9; C18 : 2 cis-9, cis-12; and C18 : 3 cis-9, cis-12, cis-15, respectively) and -C18 : 3 (60.89, 60.16 and 1.53 g/day of C18 : 1 cis-9; C18 : 2 cis-9, cis-12; and C18 : 3 cis-9, cis-12, cis-15, respectively). Dry matter intake and lactose content were not affected by the treatments, but the milk protein content was lower in cows treated with -C18 : 2 than that in CTL-treated cows. Milk yield as well as milk fat, protein and lactose yields were higher in cows treated with -C18 : 3 than the yields in CTL-treated cows, and these yields increased linearly as the unsaturation degree of the supplemental FA decreased. Compared with the CTL treatment, the -C18 : 2 treatment decreased milk C18 : 2 cis-9 content (by 2.80%) and yield (by 22.12 g/day), and the -C18 : 3 treatment decreased milk C18 : 3 cis-9, cis-12, cis-15 content (by 2.72%) and yield (by 22.33 g/day). In contrast, removing C18 : 1 cis-9 did not affect the milk content or yield of C18 : 1 cis-9. The -C18 : 2-treated cows had a higher C18 : 1 cis-9 content and tended to have a higher C18 : 1 cis-9 yield than CTL-treated cows. The yields of C8 : 0, C14 : 0 and C16 : 0 as well as

The anti-adiposity effect of bitter melon seed oil is solely attributed to its fatty acid components.

BACKGROUND: Obesity is the leading chronic disease affecting people of all ages. The objective of this study was to optimize composition of a bitter melon seed oil (BMSO) product to maximize its anti-adiposity effect. METHODS: Bleaching oil, saponifiables and non-saponifiables were prepared from BMSO, with α-eleostearic acid (α-ESA) content in BMSO maintained in bleaching oil and saponifiables. C57BL/6 J mice were allocated into five groups (n = 10/group) to receive diet C [30% soybean oil (SBO)], BM [25% SBO + 5% BMSO], BMS, BMNS or BMD. For the three latter diets, saponifiables (hydrolyzed fatty acids from BMSO), non-saponifiables (excluding fatty acids from BMSO) or bleaching oil (excluding pigments from BMSO), respectively, were added in amount equivalent to their content in 5% BMSO and SBO was added to bring total fat to 30%. After 14 wk., indices associated with adiposity and safety, as well as lipid metabolic signaling in white adipose tissue (WAT), were measured. RESULTS: The body fat percentage of mice in group BM, BMS, BMNS, and BMD were 90 ± 26, 76 ± 21, 115 ± 30 and 95 ± 17% of that in group C. Based on body fat percentage and plasma leptin concentrations, an anti-adiposity effect was evident in groups BM, BMS and BMD (greatest effect in BMS). Histologically, inguinal fat had smaller adipocytes in groups BM, BMS and BMD (P < 0.05), but not in group BMNS, relative to group C. There were no differences among groups in blood pressure or heart rate. Moreover, Sirt1 mRNA levels in inguinal fat were significantly greater in groups BM, BMS and BMD than group C. CONCLUSION: We concluded that the anti-adiposity function of BMSO was solely attributed to the fatty acid fraction, with the free fatty acid form having the greatest effect.

Incorporation and effects of punicic acid on muscle and adipose tissues of rats.

BACKGROUND: This study evaluated the effect of pomegranate seed oil (PSO) supplementation, rich in punicic acid (55 %/C18:3-9c,11 t,13c/CLNA), on the lipid profile and on the biochemical and oxidative parameters in the gastrocnemius muscle and adipose tissues of healthy rats. Linseed oil (LO), rich in linolenic acid (52 %/C18:3-9c12c15c/LNA) was used for comparison. METHODS: Male Wistar rats (n = 56) were distributed in seven groups: control (water); LNA 1 %, 2 % and 4 % (treated with LO); CLNA 1 %, 2 % and 4 % (treated with PSO), po for 40 days. The percentages were compared to the daily feed intake. Fatty acid profile were performed by gas chromatography, antioxidant enzymes activity by spectrophotometer and the adipocytes were isolated by collagenase tissue digestion. Analysis of variance (ANOVA) was applied to check for differences between the groups (control, LNAs and CLNAs) and principal component analysis (PCA) was used to project the groups in the factor-place (PC1 vs PC2) based on the biochemical responses assessed in the study. RESULTS: The fatty acids profile of tissues showed that the LNA percentages were higher in the animals that were fed LO. However, PA was only detected in the adipose tissues. Conjugated linoleic acid (CLA) was present in all the tissues of the animals supplemented with PSO, in a dose dependent manner, and 9c11t-CLA was the predominant isomer. Nevertheless there were no changes in the total weight gain of the animals, the weights of the tissues, and the oxidative stress parameters in the muscle. In addition, there was an increase in the size of the epididymal fat cells in the groups treated with PSO. Principal component analysis (PCA) showed that the CLNAs groups were arranged separately with a cumulative variance of 68.47 %. CONCLUSIONS: The results show that PSO can be used as a source of CLAs but that it does not cause changes in body modulation and does not interfere in the antioxidant activity of healthy rats.

Modeling-Enabled Characterization of Novel NLRX1 Ligands.

Nucleotide-binding domain and leucine-rich repeat containing (NLR) family are intracellular sentinels of cytosolic homeostasis that orchestrate immune and inflammatory responses in infectious and immune-mediated diseases. NLRX1 is a mitochondrial-associated NOD-like receptor involved in the modulation of immune and metabolic responses. This study utilizes molecular docking approaches to investigate the structure of NLRX1 and experimentally assesses binding to naturally occurring compounds from several natural product and lipid databases. Screening of compound libraries predicts targeting of NLRX1 by conjugated trienes, polyketides, prenol lipids, sterol lipids, and coenzyme A-containing fatty acids for activating the NLRX1 pathway. The ligands of NLRX1 were identified by docking punicic acid (PUA), eleostearic acid (ESA), and docosahexaenoic acid (DHA) to the C-terminal fragment of the human NLRX1 (cNLRX1). Their binding and that of positive control RNA to cNLRX1 were experimentally determined by surface plasmon resonance (SPR) spectroscopy. In addition, the ligand binding sites of cNLRX1 were predicted in silico and validated experimentally. Target mutagenesis studies demonstrate that mutation of 4 critical residues ASP677, PHE680, PHE681, and GLU684 to alanine resulted in diminished affinity of PUA, ESA, and DHA to NLRX1. Consistent with the regulatory actions of NLRX1 on the NF-κB pathway, treatment of bone marrow derived macrophages (BMDM)s with PUA and DHA suppressed NF-κB activity in a NLRX1 dependent mechanism. In addition, a series of pre-clinical efficacy studies were performed using a mouse model of dextran sodium sulfate (DSS)-induced colitis. Our findings showed that the regulatory function of PUA on colitis is NLRX1 dependent. Thus, we identified novel small molecules that bind to NLRX1 and exert anti-inflammatory actions.

9-Oxo-(10E,12E)-octadecadienoic acid, a cytotoxic fatty acid ketodiene isolated from eggplant calyx, induces apoptosis in human ovarian cancer (HRA) cells.

9-Oxo-(10E,12E)-octadecadienoic acid (9-EE-KODE), which is isolated from the calyx of eggplants, exhibits cytotoxic activity against human ovarian cancer (HRA) cells. The aim of the present study is to clarify the action mechanism of 9-EE-KODE leading to cell death. After the treatment of 9-EE-KODE in HRA cells, we found intracellular DNA fragmentation, surface-exposure of phosphatidylserine in the outer cell membrane, and increased caspase-3/7 activities in the HRA cells. The dissipation of mitochondrial membrane potential, release of cytochrome c from mitochondria to cytosol, down-regulation of Bcl-2, and up-regulation of Bax levels were also found in 9-EE-KODE-treated cells in a dose-dependent manner. These results demonstrated that 9-EE-KODE induced apoptosis in HRA cells via the mitochondrial regulation pathway.

Potential anti-inflammatory effects of the hydrophilic fraction of pomegranate (Punica granatum L.) seed oil on breast cancer cell lines.

In this work, we characterized conjugated linolenic acids (e.g., punicic acid) as the major components of the hydrophilic fraction (80% aqueous methanol extract) from pomegranate (Punica granatum L.) seed oil (PSO) and evaluated their anti-inflammatory potential on some human colon (HT29 and HCT116), liver (HepG2 and Huh7), breast (MCF-7 and MDA-MB-231) and prostate (DU145) cancer lines. Our results demonstrated that punicic acid and its congeners induce a significant decrease of cell viability for two breast cell lines with a related increase of the cell cycle G0/G1 phase respect to untreated cells. Moreover, the evaluation of a great panel of cytokines expressed by MCF-7 and MDA-MB-231 cells showed that the levels of VEGF and nine pro-inflammatory cytokines (IL-2, IL-6, IL-12, IL-17, IP-10, MIP-1α, MIP-1ß, MCP-1 and TNF-α) decreased in a dose dependent way with increasing amounts of the hydrophilic extracts of PSO, supporting the evidence of an anti-inflammatory effect. Taken together, the data herein suggest a potential synergistic cytotoxic, anti-inflammatory and anti-oxidant role of the polar compounds from PSO.

Induction of apoptotic cell death in HL-60 cells by jacaranda seed oil derived fatty acids.

Various fatty acids are attracting considerable interest for their anticancer effects. Among them, fatty acids containing conjugated double bonds show one of the most potent cytotoxic effects on cancer cells. Here, we focused on the cancer cell killing activity of jacaranda seed oil. The seed oil of jacaranda harvested from Miyazaki in Japan contained 30.9% cis-8, trans-10, cis-12 octadecatrienoic acid, called jacaric acid (JA). Fatty acid prepared from this oil (JFA) and JA strongly induced cell death in human leukemia HL-60 cells. On the other hand, linoleic acid and trans-10, cis-12 conjugated linoleic acid (<10 µM) did not affect cell proliferation and viability. An increase in the sub-G1 population and internucleosomal fragmentation of DNA was observed in JA- and JFA-treated cells, indicating induction of apoptotic cell death. Finally, the cytotoxic effects of JA and JFA were completely abolished by α-tocopherol. Taken together, these data suggest that jacaranda seed oil has potent apoptotic activity in HL-60 cells through induction of oxidative stress.

Jacaric acid and its octadecatrienoic acid geoisomers induce apoptosis selectively in cancerous human prostate cells: a mechanistic and 3-D structure-activity study.

Plant-derived non-essential fatty acids are important dietary nutrients, and some are purported to have chemopreventive properties against various cancers, including that of the prostate. In this study, we determined the ability of seven dietary C-18 fatty acids to cause cytotoxicity and induce apoptosis in various types of human prostate cancer cells. These fatty acids included jacaric and punicic acid found in jacaranda and pomegranate seed oil, respectively, three octadecatrienoic geometric isomers (alpha- and beta-calendic and catalpic acid) and two mono-unsaturated C-18 fatty acids (trans- and cis-vaccenic acid). Jacaric acid and four of its octadecatrienoic geoisomers selectively induced apoptosis in hormone-dependent (LNCaP) and -independent (PC-3) human prostate cancer cells, whilst not affecting the viability of normal human prostate epithelial cells (RWPE-1). Jacaric acid induced concentration- and time-depedent LNCaP cell death through activation of intrinsic and extrinsic apoptotic pathways resulting in cleavage of PARP-1, modulation of pro- and antiapoptotic Bcl-2 family of proteins and increased cleavage of caspase-3, -8 and -9. Moreover, activation of a cell death-inducing signalling cascade involving death receptor 5 was observed. Jacaric acid induced apoptosis in PC-3 cells by activation of the intrinsic pathway only. The spatial conformation cis, trans, cis of jacaric and punicic acid was shown to play a key role in the increased potency and efficacy of these two fatty acids in comparison to the five other C-18 fatty acids tested. Three-dimensional conformational analysis using the PubChem Database (http://pubchem.ncbi.nlm.nih.gov) showed that the cytotoxic potency of the C-18 fatty acids was related to their degree of conformational similarity to our cytotoxic reference compound, punicic acid, based on optimized shape (ST) and feature (CT) similarity scores, with jacaric acid being most 'biosimilar' (ST(ST-opt)=0.81; CT(CT-opt)=0.45). This 3-D analysis of structural similarity enabled us to rank geoisomeric fatty acids according to cytotoxic potency, whereas a 2-D positional assessment of cis/trans structure did not. Our findings provide mechanistic evidence that nutrition-derived non-essential fatty acids have chemopreventive biological activities and Exhibit 3-D structure-activity relationships that could be exploited to develop new strategies for the prevention or treatment of prostate cancer regardless of hormone dependency.

Protective effect of conjugated linolenic acid isomers present in vegetable oils against arsenite-induced renal toxicity in rat model.

OBJECTIVE: The aim of the present study was to investigate the protective effect of conjugated linolenic acid (CLnA), present in vegetable oils against arsenite-induced renal oxidative stress. METHODS: Albino rats were divided into six groups. Group 1 was control and group 2 was treated with sodium arsenite (Sa; 10 mg/kg BW). Rats in groups 3 and 4 were treated with mixture of α-eleostearic acid and punicic acid (1:1) (0.5% and 1.0%, respectively), whereas rats in the groups 5 and 6 were treated with 0.5% of α-eleostearic acid and 0.5% of punicic acid, respectively, along with Sa by oral gavage once daily. RESULTS: Results revealed that activity of antioxidant enzymes and total reduced glutathione content, total protein content, and phospholipid content in kidney were decreased significantly in arsenite-treated group compared with control. Activity of nitric oxide synthase, peroxidation of lipid, protein oxidation, total cholesterol content, total lipid content of kidney, and plasma creatinine level were increased significantly (P < 0.05) in arsenite-treated rats compared with control. Fatty-acid composition of renal lipids showed significant decrease in monounsaturated fatty acid, polyunsaturated fatty acid (PUFA) content, and increase in saturated fatty acid content due to oxidative stress. PUFA such as γ-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid decreased significantly with significant (P < 0.05) increase in arachidonic acid content after Sa treatment. Administration of blended product of both the isomers caused better restoration of renal fatty acids and other altered parameters. CONCLUSION: CLnA isomers caused amelioration of renal oxidative stress and the isomers showed synergistic activity.

Responses to oleic, linoleic and α-linolenic acids in high-carbohydrate, high-fat diet-induced metabolic syndrome in rats.

We investigated the changes in adiposity, cardiovascular and liver structure and function, and tissue fatty acid compositions in response to oleic acid-rich macadamia oil, linoleic acid-rich safflower oil and α-linolenic acid-rich flaxseed oil (C18 unsaturated fatty acids) in rats fed either a diet high in simple sugars and mainly saturated fats or a diet high in polysaccharides (cornstarch) and low in fat. The fatty acids induced lipid redistribution away from the abdomen, more pronounced with increasing unsaturation; only oleic acid increased whole-body adiposity. Oleic acid decreased plasma total cholesterol without changing triglycerides and nonesterified fatty acids, whereas linoleic and α-linolenic acids decreased plasma triglycerides and nonesterified fatty acids but not cholesterol. α-Linolenic acid improved left ventricular structure and function, diastolic stiffness and systolic blood pressure. Neither oleic nor linoleic acid changed the left ventricular remodeling induced by high-carbohydrate, high-fat diet, but both induced dilation of the left ventricle and functional deterioration in low fat-diet-fed rats. α-Linolenic acid improved glucose tolerance, while oleic and linoleic acids increased basal plasma glucose concentrations. Oleic and α-linolenic acids, but not linoleic acid, normalized systolic blood pressure. Only oleic acid reduced plasma markers of liver damage. The C18 unsaturated fatty acids reduced trans fatty acids in the heart, liver and skeletal muscle with lowered stearoyl-CoA desaturase-1 activity index; linoleic and α-linolenic acids increased accumulation of their C22 elongated products. These results demonstrate different physiological and biochemical responses to primary C18 unsaturated fatty acids in a rat model of human metabolic syndrome.

Diet enriched with korean pine nut oil improves mitochondrial oxidative metabolism in skeletal muscle and brown adipose tissue in diet-induced obesity.

In this study, we investigated effects of pine nut oil (PNO) on high-fat-diet (HFD)-induced obesity and metabolic dysfunction in skeletal muscle and brown adipose tissue (BAT). Male C57BL/6 mice were fed a HFD with 15% energy from lard and 30% energy from either soybean oil (SBO-HFD) or PNO (PNO-HFD) for 12 weeks. The PNO-HFD resulted in less weight gain and intramuscular lipid accumulation than the SBO-HFD and was accompanied by upregulation of transcripts and proteins related to oxidative metabolism and phosphorylation of AMP-activated protein kinase (AMPK), as well as molecules selectively expressed in type I and type IIa muscle fibers. In addition, uncoupling protein-1 was upregulated in BAT. These beneficial metabolic effects were partly associated with the dual ligand activity of pinolenic acid, which is abundant in PNO, for peroxisome proliferator-activated receptors α and δ. Our findings suggest that PNO may have potential as a dietary supplement for counteracting obesity and metabolic dysregulation.

Bitter melon seed oil-attenuated body fat accumulation in diet-induced obese mice is associated with cAMP-dependent protein kinase activation and cell death in white adipose tissue.

The aim of this study was to investigate the antiadiposity effect of bitter melon seed oil (BMSO), which is rich in the cis-9, trans-11, trans-13 isomer of conjugated linolenic acid. In Expt. 1, C57BL/6J mice were fed a butter-based, high-fat diet [HB; 29% butter + 1% soybean oil (SBO)] for 10 wk to induce obesity. They then continued to receive that diet or were switched to an SBO-based, high-fat diet alone (HS; 30% SBO) or containing bitter melon seed oil (BMSO) (HBM; 15% SBO + 15% BMSO) for 5 wk. The body fat percentage was significantly lower in mice fed the HBM diet (21%), but not the HS diet, compared with mice fed the HB diet. In Expt. 2, mice were fed an SBO-based, high-fat diet containing 0 (HS), 5 (LBM), 10 (MBM), or 15% (HBM) BMSO for 10 wk. In the LBM, MBM, and HBM groups, the body fat percentage was significantly lower by 32, 35, and 65%, respectively, compared with the HS control. The reduction in the HBM group was significantly greater than that in the LBM or MBM group. BMSO administration increased phosphorylation of acetyl-CoA carboxylase, cAMP-activated protein kinase (PKA), and signal transducer and activator of transcription 3 in the white adipose tissue (WAT), suggesting that PKA and leptin signaling might be involved in the BMSO-mediated reduction in lipogenesis and increase in thermogenesis and lipolysis. However, compared with the HS control, the HBM group had a significantly higher TNFα concentration in the WAT accompanied by TUNEL-positive nuclei. We conclude that BMSO is effective in attenuating body fat accumulation through mechanisms associated with PKA activation and programmed cell death in the WAT, but safety concerns need to be carefully addressed.

Xanthigen suppresses preadipocyte differentiation and adipogenesis through down-regulation of PPARγ and C/EBPs and modulation of SIRT-1, AMPK, and FoxO pathways.

Xanthigen is a source of punicic acid and fucoxanthin derived from pomegranate seed and brown seaweed, respectively with recognized triacylglycerol-lowering effects in humans, yet the mechanism remains to be fully elucidated. The present study investigated the inhibitory effects of Xanthigen, fucoxanthin, and punicic acid (70% in pomegranate seed oil) on the differentiation of 3T3-L1 preadipocytes. Xanthigen potently and dose-dependently suppressed accumulation of lipid droplets in adipocytes compared to its individual components, fucoxanthin and pomegranate seed oil. Western blot analysis revealed that Xanthigen markedly down-regulated the protein levels of key adipogenesis transcription factors peroxisome proliferator-activated receptor (PPAR)γ, CCAAT/enhancer binding protein (C/EBP) ß, and C/EBPδ as well as a key enzyme involved in adipogenesis, fatty acid synthase (FAS). Xanthigen up-regulated the NAD(+)-dependent histone deacetylases (SIRT1) and activated AMP-activated protein kinase (AMPK) signaling in differentiated 3T3-L1 adipocytes. In addition, Xanthigen may also stimulate insulin trigger signaling and result in Akt-dependent phosphorylation of forkhead/winged helix O (FoxO)1 and FoxO3a. These results indicate that Xanthigen suppresses adipocyte differentiation and lipid accumulation through multiple mechanisms and may have applications for the treatment of obesity.