Chrononutritional Effects of Cherry Consumption on Hepatic Lipid Profile

The phytochemical composition of fruits, especially polyphenols, depends on the environmental conditions under which these fruits are cultivated and the agronomic practices followed. Therefore, the consumption of fruits from different origins, with different polyphenol signatures, could have differential effects on health. In addition, recent studies have shown that variation in the biological rhythms due to changes in the photoperiod in the different seasons differentially affect the metabolism in animal models, thus conditioning their response to food consumption. Considering all, this article evaluates the effects of consumption of sweet cherry from different sources, local (LC) and non-local (nLC), on plasma metabolic parameters and the gene expression of key enzymes of lipid metabolism in Fischer 344 rats under photoperiods simulating different seasons. Animals were classified into three photoperiods (L6, L12 and L18) and three treatments (LC, nLC and VH). Both the photoperiod and the treatments significantly affected the evaluated parameters. An effect of the photoperiod on triacylglycerides, non-esterified fatty acids and the mRNA concentration of crucial enzymes from the hepatic lipid metabolism was observed. Furthermore, the consumption of fruit in L12 lowered blood glucose, while the different treatments affected the hepatic expression of genes related with lipidic enzymes.

Glucocorticoids (GCs) play critical roles in adipose tissue metabolism. Here, we compare in a mouse model the effects of chronic glucocorticoid excess and diet-induced obesity on white adipose tissue mass and distribution, by focusing on visceral adipose tissue (VAT) fatty acid composition changes, the role of de novo lipogenesis (DNL) and the inflammatory state. We used a noninvasive mouse model of hypercortisolism to compare GC-induced effects on adipose tissue with diet-induced obesity [high-fat diet (HFD) 45%] and control mice after 10 wk of treatment. Subcutaneous adipose tissue (SAT) and VAT mass and distribution were measured by nuclear magnetic resonance imaging (NMRI). Fatty acid composition in VAT was analyzed by NMR spectroscopy and gas chromatography. Gene expression of key enzymes involved in DNL was analyzed in liver and VAT. Macrophage infiltration markers and proinflammatory cytokines were measured by gene expression in VAT. HFD or GC treatment induced similar fat mass expansion with comparable distribution between SAT and VAT depots. However, in VAT, GCs induce DNL, higher palmitic acid (PA), macrophage infiltration, and proinflammatory cytokine levels, accompanied by systemic nonesterified fatty acid (NEFA) elevation, hyperinsulinemia, and higher homeostatic model assessment for insulin resistance (HOMA-IR) levels compared with diet-induced obesity. Thus, chronic hypercortisolism induces DNL and fatty acid composition changes toward increased SFA and reduced polyunsaturated fatty acid (PUFA) levels in VAT, promoting macrophage recruitment and proinflammatory cytokines, suggesting a worse cardiometabolic profile even compared with HFD mice.

Over the past 100 years, changes in the food supply in Western nations have resulted in alterations in dietary fatty acid consumption, leading to a dramatic increase in the ratio of omega-6 (omega6) to omega3 polyunsaturated fatty acids (PUFA) in circulation and in tissues. Increased omega6/omega3 ratios are hypothesized to increase inflammatory mediator production, leading to higher incidence of inflammatory diseases, and may impact inflammatory gene expression. To determine the effect of reducing the omega6/omega3 ratio on expression of inflammatory pathway genes in mononuclear cells, healthy humans were placed on a controlled diet for 1 week, then given fish oil and borage oil for an additional 4 weeks. Serum and neutrophil fatty acid composition and ex vivo leukotriene B(4) production from stimulated neutrophils were measured at the start and end of the supplementation period and after a 2-week washout. RNA was isolated from mononuclear cells and expression of PI3K, Akt, NFkappaB, and inflammatory cytokines was measured by real-time PCR. A marked increase was seen in serum and neutrophil levels of long-chain omega3 PUFA concomitant with a reduction in the omega6/omega3 PUFA ratio (40%). The ex vivo capacity of stimulated neutrophils to produce leukotriene B(4) was decreased by 31%. Expression of PI3Kalpha and PI3Kgamma and the quantity of PI3Kalpha protein in mononuclear cells was reduced after supplementation, as was the expression of several proinflammatory cytokines. These data reveal that PUFA may exert their clinical effects via their capacity to regulate the expression of signal transduction genes and genes for proinflammatory cytokines.

Tartary buckwheat, a polygonaceae family plant, is rich in abundant flavonoids, high-quality protein, and well-balanced essential amino acids. This study aimed to investigate the effects of climatic variables on the quality of Tartary buckwheat. In this study, six distinct types of Tartary buckwheat collected from the Sichuan Basin, Western Sichuan Plateau, and Yunnan-Guizhou Plateau in southwest China were chosen to investigate the impact of climatic conditions from the grain-filling stage to the harvest stage on the concentration of flavonoids and expression of key enzyme genes involved the synthesis of flavonoids. Meteorological data of three producing areas were collected from the China Meteorological Network, mainly including maximum temperature (Tmax), minimum temperature (Tmin), diurnal temperature difference (Tdif), and light intensity. Then, the contents of rutin, kaempferol-3-O-rutin glycoside, quercetin, and kaempferol in 30 batches of Tartary buckwheat from 6 varieties including Chuanqiao No. 1, Chuanqiao No. 2, Xiqiao No. 1, Xiqiao No. 2, Miqiao No. 1 and Di ku were determined by ultra performance liquid chromatography-mass spectrometry (UPLC-MS/MS). Furthermore, the expression levels of phenylalanine ammonia lyase (PAL), 4-coumaric acid coenzyme A ligase (4CL), and anthocyanin synthase (ANS) in six kinds of Tartary buckwheat were detected by real-time polymerase chain reaction (PCR). The seed photos were processed by ImageJ processing software. The partial least squares method was used to analyze the correlation. As a result, light intensity can promote the accumulation of flavonoids and the expression of key enzyme genes. Miqiao No. 1, which grows in Liangshan Prefecture, Sichuan Province, has the highest light intensity and is the dominant variety with flavonoid content. More importantly, the expression levels of PAL and 4CL in the secondary metabolic pathway of flavonoids were positively correlated with the content of Tartary buckwheat flavonoids. Interestingly, the expression level of ANS was negatively correlated with the content of PAL, 4CL, and flavonoids. In addition, ANS is a key gene affecting the seed coat color of Tartary buckwheat. The higher the expression of ANS, the darker the seed coat color. These findings provide a theoretical basis and reference for the breeding of fine buckwheat varieties.

Chronic alcohol consumption is associated with fatty liver disease in mammals. The object of this study was to gain an understanding of dysregulated lipid metabolism in alcohol-fed C57BL/6 mice using a targeted lipidomic approach. Liquid chromatography tandem mass spectrometry was used to analyze several lipid classes, including free fatty acids, fatty acyl-CoAs, fatty acid ethyl esters, sphingolipids, ceramides, and endocannabinoids, in plasma and liver samples from control and alcohol-fed mice. The interpretation of lipidomic data was augmented by gene expression analyses for important metabolic enzymes in the lipid pathways studied. Alcohol feeding was associated with i) increased hepatic free fatty acid levels and decreased fatty acyl-CoA levels associated with decreased mitochondrial fatty acid oxidation and decreased fatty acyl-CoA synthesis, respectively; ii) increased hepatic ceramide levels associated with higher levels of the precursor molecules sphingosine and sphinganine; and iii) increased hepatic levels of the endocannabinoid anandamide associated with decreased expression of its catabolic enzyme fatty acid amide hydrolase. The unique combination of lipidomic and gene expression analyses allows for a better mechanistic understanding of dysregulated lipid metabolism in the development of alcoholic fatty liver disease.

Thioesterase activity is typically required for the release of products from polyketide synthase enzymes, but no such enzyme has been characterized in deep-sea bacteria associated with the production of polyunsaturated fatty acids. In this work, we have expressed and purified the Orf6 thioesterase from Photobacterium profundum. Enzyme assays revealed that Orf6 has a higher specific activity toward long-chain fatty acyl-CoA substrates (palmitoyl-CoA and eicosapentaenoyl-CoA) than toward short-chain or aromatic acyl-CoA substrates. We determined a high resolution (1.05 Å) structure of Orf6 that reveals a hotdog hydrolase fold arranged as a dimer of dimers. The putative active site of this structure is occupied by additional electron density not accounted for by the protein sequence, consistent with the presence of an elongated compound. A second crystal structure (1.40 Å) was obtained from a crystal that was grown in the presence of Mg(2+), which reveals the presence of a binding site for divalent cations at a crystal contact. The Mg(2+)-bound structure shows localized conformational changes (root mean square deviation of 1.63 Å), and its active site is unoccupied, suggesting a mechanism to open the active site for substrate entry or product release. These findings reveal a new thioesterase enzyme with a preference for long-chain CoA substrates in a deep-sea bacterium whose potential range of applications includes bioremediation and the production of biofuels.

This issue of Circulation contains an article1 that I believe deserves special attention from cardiologists and physicians. It reports the 46-month mean follow-up findings on the original report of the study on “Mediterranean α-linolenic acid–rich diet in secondary prevention of coronary heart disease,” the so-called Lyon Diet Heart Study. This study was undertaken because of the interest of the investigators in explaining the very much lower mortality from cardiovascular disease, mainly coronary heart disease, in the countries bordering the Mediterranean compared with that in northern Europe. The initial report2 was published in Lancet in 1994 after the study was terminated by its Scientific and Ethics Committee at 27 months mean follow-up time of what had been planned as a 5-year study, because the benefits in the experimental group at that time were so favorable. Despite the striking findings in the first report of a 70% reduction in all-cause mortality due to a reduction in coronary heart disease (CHD) mortality and comparable large reductions in nonfatal sequelae, I have encountered few cardiologists here who are aware of that study. It is much to the credit of Dr de Lorgeril and associates that they persisted in following the original enrollees despite the official termination of the study and publication of the initial findings so that they are now able to report their more extended observations. With the mean follow-up time of 46 months per patient, the initial remarkably beneficial effects of the experimental dietary program persisted compared with the control group consuming the “prudent Western-type diet.” Let me list the several important messages I believe are inherent in the results that are clearly and modestly presented in this article. 1. At a time when health professionals, the pharmaceutical industries, and the research funding and regulatory agencies are almost totally focused …

Omega-3 Fatty Acids for Maintenance of Remission of Crohn's Disease

Objectives The work intended to reveal the effect of cold shock (CS) treatment on chilling injury (CI), antioxidant capacity, and membrane fatty acid of peach fruit. Materials and methods Peaches were soaked in ice water (0 °C) for 10 min and stored at 5 °C for 28 days for determination, except CI, and then stored for 3 days at 20 °C, only CI was measured. The electrolyte leakage (EL) was measured by conductivity meter. The activities of antioxidant enzymes (superoxide dismutase, ascorbate peroxidase, catalase, and peroxidase) and key enzymes of membrane lipid metabolism (phospholipase D, lipase, and lipoxygenase) as well as reactive oxygen species (ROS; O2·– and H2O2) were measured with a spectrophotometer. An ELISA kit and gas chromatography were used to determine membrane lipids and membrane fatty acids. The relative gene expression was measured by real-time polymerase chain reaction analysis. Results The results showed that CS treatment effectively delayed CI, suppressed the increase of EL and malondialdehyde content. Meanwhile, CS-treated fruit exhibited lower level of ROS and higher activities of antioxidant enzymes. Furthermore, CS treatment inhibited the activities as well as the relative gene expression of key enzymes in membrane lipid metabolism. CS-treated fruits maintained higher membrane fatty acid unsaturation and lower phosphatidic acid content. Conclusions These results indicated that CS treatment effectively alleviated CI and maintained the integrity of cell membranes by inducing antioxidant-related enzyme activity and maintaining a higher ratio of unsaturated fatty acids to saturated fatty acids.

Transcriptome analysis revealing the effect of Bupleurum scorzonerifolium Willd association with endophytic fungi CHS3 on the production of saikosaponin D

Compared with other mammalian tissues, retina is highly enriched in PUFA. Long-chain PUFA (LC-PUFA; C18-C24) are essential FAs that are enriched in the retina and are necessary for maintenance of normal retinal development and function. The retina, brain, and sperm also contain very LC-PUFA (VLC-PUFA; >C24). Although VLC-PUFA were discovered more than two decades ago, very little is known about their biosynthesis and functional roles in the retina. This is due mainly to intrinsic difficulties associated with working on these unusually long polyunsaturated hydrocarbon chains and their existence in small amounts. Recent studies on the FA elongase elongation of very long chain fatty acids-4 (ELOVL4) protein, however, suggest that VLC-PUFA probably play some uniquely important roles in the retina as well as the other tissues. Mutations in the ELOVL4 gene are found in patients with autosomal dominant Stargardt disease. Here, we review the recent literature on VLC-PUFA with special emphasis on the elongases responsible for their synthesis. We focus on a novel elongase, ELOVL4, involved in the synthesis of VLC-PUFA, and the importance of these FAs in maintaining the structural and functional integrity of retinal photoreceptors.

Dietary inclusion of insect oil: Impact on growth, nutrient utilisation, lipid metabolism, antioxidant and immune-related responses in European catfish (Silurus glanis L)

High fat intake is associated with fat mass gain through fatty acid activation of peroxisome proliferator-activated receptors delta and gamma, which promote adipogenesis. We show herein that, compared to a combination of specific agonists to both receptors or to saturated, monounsaturated, and omega-3 polyunsaturated fatty acids, arachidonic acid (C20:4, omega-6) promoted substantially the differentiation of clonal preadipocytes. This effect was blocked by cyclooxygenase inhibitors and mimicked by carbacyclin, suggesting a role for the prostacyclin receptor and activation of the cyclic AMP-dependent pathways that regulate the expression of the CCAAT enhancer binding proteins beta and delta implicated in adipogenesis. During the pregnancy-lactation period, mother mice were fed either a high-fat diet rich in linoleic acid, a precursor of arachidonic acid (LO diet), or the same isocaloric diet enriched in linoleic acid and alpha-linolenic acid (LO/LL diet). Body weight from weaning onwards, fat mass, epididymal fat pad weight, and adipocyte size at 8 weeks of age were higher with LO diet than with LO/LL diet. In contrast, prostacyclin receptor-deficient mice fed either diet were similar in this respect, indicating that the prostacyclin signaling contributes to adipose tissue development. These results raise the issue of the high content of linoleic acid of i) ingested lipids during pregnancy and lactation, and ii) formula milk and infant foods in relation to the epidemic of childhood obesity.

Polyunsaturated fatty acids (FA) regulate genes involved in lipid metabolism. The effects of polyunsaturated FA on the transcription factor adipocyte determination and differentiation-dependent factor (ADD) 1 and fatty acid synthase (FAS) mRNA in differentiating porcine adipocytes were measured using a stromal vascular cell culture system. Porcine stromal vascular cells were isolated from subcutaneous adipose tissues and plated in Dulbecco's modified Eagle's medium (DMEM)-nutrient mixture F-12 Ham (F-12) plus fetal bovine serum (100 ml/l) for 24 h. Then cells were differentiated in DMEM-F12 plus insulin, hydrocortisone and transferrin without or with polyunsaturated FA at 6.25, 25.00 or 100.00 microM. The ADD1 mRNA was decreased by 100.00 microM-arachidonic acid, 6.25 to 100.00 microM-docosahexaenoic acid or cis-9,trans-11-conjugated linoleic acid. The polyunsaturated FA reduced the transcription rate of FAS, but not of ADD1. All three polyunsaturated FA accelerated degradation of ADD1 and FAS mRNA to reduce the abundance of ADD1 and FAS mRNA. Results also showed that polyunsaturated FA inhibit the ADD1 expression, not only of mRNA concentration, but also of mature ADD1 protein concentration, suggesting an overall reduction of ADD1 function by polyunsaturated FA. Our present experiments demonstrate that polyunsaturated FA regulate the gene expression of ADD1 and enzymes involved in lipid metabolism in porcine adipocytes.

Accumulation of lipid in nonadipose tissues plays a critical role in the pathogenesis of a diverse array of chronic diseases, including diabetes and heart failure. Normal cellular homeostasis relies on a critical balance of fuel uptake and utilization that is controlled by elaborate transcriptional networks, which ensure that cellular energy needs are consistently met and toxic intermediates do not accumulate. This process is particularly important for the heart, which has a continuous high energy demand. The heart meets this demand by dynamically shifting its preference for glucose and fatty acids in various physiologic and pathologic circumstances. This change is driven by alterations in signaling networks and regulated expression of key metabolic genes. While the heart predominantly relies on fatty acids as a fuel source, under normal conditions the myocardium is not a site of significant lipid storage. Moreover, conditions that promote fatty acid excess, such as insulin resistance and diabetes, are associated with detrimental effects on cardiac function. Evidence has emerged that fatty acid overload may damage the myocardium through excessive fatty acid oxidation and accumulation of toxic lipid species within the myocardium. These toxic effects have been termed “lipotoxicity” (1). A number of investigators have implicated specific lipid species, such as long-chain saturated fatty acids (palmitate), in the pathogenesis of cardiomyocyte dysfunction (2, 3), while unsaturated fatty acids (oleate) are considered cardioprotective (4). The mechanism whereby some fatty acid species exert more toxic effects than others is poorly understood. In this issue of The Journal of Lipid Research, Lockridge et al. (5) report microarray data of the differential effects of several fatty acid species in adult cardiac myocytes. Previous investigations have primarily evaluated direct effects of individual fatty acid species in neonatal rat cardiac myocytes, where the expression of key metabolic regulators is still changing. Thus, the work by Lockridge et al. provides new insight into effects in a mature cardiac myocyte and does this in a systematic and unbiased manner. The most striking finding in this study was the dramatic effect of the long-chain saturated fatty acid palmitate on gene expression for enzymes involved in the endoplasmic reticulum (ER) stress response and apoptosis pathways as well as markers of DNA damage. These findings are consistent with other recent data in CHO cells, in which palmitate was found to be trafficked to the ER and to have dramatic effects on ER structure and integrity as well as to disrupt mitochondrial function (6). Furthermore, ER stress has been implicated in apoptosis of pancreatic b cells from type 2 diabetic models (7). Taken together, this recent evidence strongly implicates ER stress in the cellular dysfunction associated with palmitate exposure. Further studies specifically evaluating the ER stress response in cardiac myocytes will be important in understanding the mechanisms of cardiac dysfunction associated with lipid overload and in targeting potential therapies to alleviate cardiomyopathy associated with diabetes. Interestingly, Borradaile et al. (6) also found that induction of fatty acid oxidation minimized the effects on ER integrity upon exposure to palmitate. Lockridge et al. (5) demonstrated differential effects of oleate versus palmitate on gene expression for a number of enzymes that play a role in upregulating mitochondrial fatty acid oxidation pathways (e.g., Cpt1a, Fatp1, and Ucp3). While palmitate also upregulated many components of mitochondrial oxidative pathways, the more robust effect of oleate on some of these genes is intriguing. One of the genes the authors highlight that is specifically induced by oleate is Ucp3. They suggest that upregulation of Ucp3 may result in increased recycling of free CoA and thus promote the oxidation of oleate, whereas palmitate may be more likely to accumulate in the mitochondria, leading to cytotoxic effects. Further studies to evaluate this hypothesis will be important for understanding the fate of fatty acid species within the cell and potentially to assist in identifying targets for cellular rescues. One such study might investigate the potential for unsaturated fatty acids to serve as preferential ligands for the peroxisome proliferator-activated receptor family, which is known to modulate fatty acid uptake and oxidation.