Jianheng Shen

Increased hypolipidemic benefits of cis-9, trans-11 conjugated linoleic acid in combination with trans-11 vaccenic acid in a rodent model of the metabolic syndrome, the JCR:LA-cp rat

BackgroundConjugated linoleic acid (cis-9, trans-11 CLA) and trans-11 vaccenic acid (VA) are found naturally in ruminant-derived foods. CLA has been shown to have numerous potential health related effects and has been extensively investigated. More recently, we have shown that VA has lipid-lowering properties associated with reduced hepatic lipidogenesis and chylomicron secretion in the JCR:LA-cp rat. The aim of this study was to evaluate potential additional hypolipidemic effects of purified forms of CLA and VA in an animal model of the metabolic syndrome (the JCR:LA-cp rat).MethodsTwenty four obese JCR:LA-cp rats were randomized and assigned to one of three nutritionally adequate iso-caloric diets containing 1% w/w cholesterol and 15% w/w fat for 16 wk: 1) control diet (CD), 2) 1.0% w/w cis-9, trans-11 CLA (CLA), 3) 1.0% w/w VA and 1% w/w cis-9, trans-11 CLA (VA+CLA). Lean rats were fed the CD to represent normolipidemic conditions.ResultsFasting plasma triglyceride (TG), total cholesterol and LDL-cholesterol concentrations were reduced in obese rats fed either the CLA diet or the VA+CLA diet as compared to the obese control group (p < 0.05, p < 0.001; p < 0.001, p < 0.01; p < 0.01, p < 0.001, respectively). The VA+CLA diet reduced plasma TG and LDL-cholesterol to the level of the normolipidemic lean rats and further decreased nonesterified fatty acids compared to the CLA diet alone. Interestingly, rats fed the VA+CLA diet had a higher food intake but lower body weight than the CLA fed group (P < 0.05). Liver weight and TG content were lower in rats fed either CLA (p < 0.05) or VA+CLA diets (p < 0.001) compared to obese control, consistent with a decreased relative protein abundance of hepatic acetyl-CoA carboxylase in both treatment groups (P < 0.01). The activity of citrate synthase was increased in liver and adipose tissue of rats fed, CLA and VA+CLA diets (p < 0.001) compared to obese control, suggesting increased mitochondrial fatty acid oxidative capacity.ConclusionWe demonstrate that the hypolipidemic effects of chronic cis-9, trans-11 CLA supplementation on circulating dyslipidemia and hepatic steatosis are enhanced by the addition of VA in the JCR:LA-cp rat.

Diets enriched in trans-11 vaccenic acid alleviate ectopic lipid accumulation in a rat model of NAFLD and metabolic syndrome

Trans11-18:1 (vaccenic acid, VA) is one of the most predominant naturally occurring trans fats in our food chain and has recently been shown to exert hypolipidemic effects in animal models. In this study, we reveal new mechanism(s) by which VA can alter body fat distribution, energy utilization and dysfunctional lipid metabolism in an animal model of obesity displaying features of the metabolic syndrome (MetS). Obese JCR:LA-cp rats were assigned to a control diet that included dairy-derived fat or the control diet supplemented with 1% VA. VA reduced total body fat (-6%), stimulated adipose tissue redistribution [reduced mesenteric fat (-17%) while increasing inguinal fat mass (29%)] and decreased adipocyte size (-44%) versus control rats. VA supplementation also increased metabolic rate (7%) concomitantly with an increased preference for whole-body glucose utilization for oxidation and increased insulin sensitivity [lower HOMA-IR (-59%)]. Further, VA decreased nonalcoholic fatty liver disease activity scores (-34%) and reduced hepatic (-27%) and intestinal (-39%) triglyceride secretion relative to control diet, while exerting differential transcriptional regulation of SREBP1 and FAS amongst other key genes in the liver and the intestine. Adding VA to dairy fat alleviates features of MetS potentially by remodeling adipose tissue and attenuating ectopic lipid accumulation in a rat model of obesity and MetS. Increasing VA content in the diet (naturally or by fortification) may be a useful approach to maximize the health value of dairy-derived fats.

The intestinal bioavailability of vaccenic acid and activation of peroxisome proliferator‐activated receptor‐α and ‐γ in a rodent model of dyslipidemia and the metabolic syndrome

SCOPE Evidence suggests a neutral to beneficial role of certain trans fatty acids (TFA) from natural ruminant sources. Trans11-18:1 (vaccenic acid, VA), the most predominant ruminant TFA and a precursor to conjugated linoleic acid, has been shown to improve atherogenic dyslipidemia and symptoms of hepatic steatosis in animal models. The objective of this study was to assess the intestinal bioavailability of various VA sources including synthetic free fatty acid (FFA) and natural ruminant triglyceride forms, as well as the mechanistic pathways that mediate VAs bioactivity. METHODS AND RESULTS VA acts as a partial agonist to both peroxisome proliferator-activated receptors (PPAR)-α and PPAR-γ in vitro, with similar affinity compared to commonly known PPAR agonists. It was further confirmed that VA at 30 and 100 μM concentrations suppressed cardiomyocyte hypertrophy vitro in a PPAR-α- and PPAR-γ-dependent manner. In vivo, feeding of VA (1%, w/w) resulted in increased mRNA and protein expression of PPAR-γ in the mucosa of JCR:LA-cp rats, a model of the metabolic syndrome (p < 0.01 and p < 0.05, respectively) compared to control. In addition, VA from a triglyceride source had greater intestinal bioavailability in vivo compared to VA provided in an FFA form (p < 0.01). CONCLUSION The activation of PPAR-α- and PPAR-γ-dependent pathways provides a mechanistic explanation of how VA improves blood lipids and related metabolic disorders during conditions of hyperlipidemia. This report also supports the consideration of differential reporting of industrially produced versus natural TFA on food nutrient labels.

Rapid NMR method for the quantification of organic compounds in thin stillage.

Thin stillage contains organic and inorganic compounds, some of which may be valuable fermentation coproducts. This study describes a thorough analysis of the major solutes present in thin stillage as revealed by NMR and HPLC. The concentration of charged and neutral organic compounds in thin stillage was determined by excitation sculpting NMR methods (double pulse field gradient spin echo). Compounds identified by NMR included isopropanol, ethanol, lactic acid, 1,3-propanediol, acetic acid, succinic acid, glycerophosphorylcholine, betaine, glycerol, and 2-phenylethanol. The concentrations of lactic and acetic acid determined with NMR were comparable to those determined using HPLC. HPLC and NMR were complementary, as more compounds were identified using both methods. NMR analysis revealed that stillage contained the nitrogenous organic compounds betaine and glycerophosphorylcholine, which contributed as much as 24% of the nitrogen present in the stillage. These compounds were not observed by HPLC analysis.

Rapid reversed-phase liquid chromatography separation of cyclolinopeptides with monolithic and microparticulate columns.

Three monolithic C(18)-bonded silica gel columns i.e. Chromolith SpeedROD (CSR), Chromolith Performance (CP), and Chromolith High Resolution (CHR), MerckKGaA Darmstadt, Germany and two particle-based columns i.e. ZORBAX Eclipse XDB-C(18) (ZEX), Agilent and POROS R1/20 (POR), Applied Biosystems were compared for their performance in separating a mixture of flaxseed cyclolinopeptides (CLs). Gradient mobile phases of acetonitrile and water were optimized for each column. The performance of CHR column in profiling CL standards, measured as the resolution of individual CL, selectivity, and peak asymmetry exceeded the performance of traditional particle-packed columns and the other monolithic columns. The profiling of CLs in aqueous methanolic flaxseed extract was optimized for high-throughput analysis. A total analysis time of 1.5 min at a flow rate of 3.0mLmin(-1) was achieved on a CSR column. Injection of over 2000 methanol extracts of flaxseed on a CSR column had no impact on backpressure or resolution of a standard CL mixture.

Cyclo-linopeptide A methanol solvate.

Crystals of the title compound, C57H85N9O9·CH4O, the methanol solvate of a nine peptide polypeptide, cyclo-(Pro-Pro-Phe-Phe-Leu-Ile-Ile-Leu-Val), were obtained after separation of the cyclic peptide from flax oil. The cyclolinopeptide A (CLP-A) molecules are linked in chains along the a axis by N—H⋯O hydrogen bonds. Each methanol O atom is hydrogen bonded to one O atom and two N—H groups in the same CLP-A molecule. There are a total of eight hydrogen bonds in each CLP-A–MeOH unit.

Dietary supplementation of trans-11-vaccenic acid reduces adipocyte size but neither aggravates nor attenuates obesity-mediated metabolic abnormalities in fa/fa Zucker rats.

Conjugated linoleic acid (CLA) present in dairy and ruminant fat has beneficial effects on metabolic syndrome characteristics in humans and some rodent models. Production practices to increase the milk content of CLA are also substantially elevating trans-11-vaccenic acid (VA). Questions are being raised whether VA has the same beneficial actions as CLA or has adverse biological effects similar to industrially produced trans-fatty acids. The present study examined the effects of dietary supplementation of either 0 or 1·5 % (w/w) VA for 8 weeks on lipidaemia, glycaemia, blood pressure, hepatic steatosis, adipocyte size and molecular markers of inflammation and insulin signalling in fa/fa Zucker rats. Dietary supplementation of VA did not alter feed intake, weight gain, blood pressure or organ:body weight (BW) ratios, except the epididymal fat:BW ratio which was lower in the VA group compared with the control group. The total liver lipid concentration as an indicator of hepatic steatosis was not different between the groups. Likewise, there were no changes in fasting lipidaemia, glycaemia or oral glucose tolerance. Although there were no physiological differences observed between the groups, animals supplemented with VA had smaller adipocytes (approximately 7 % smaller than the controls). The VA group also had higher adipophilin and IL-10 protein levels in epididymal adipose tissue (1·7- and 1·4-fold higher than the controls, respectively); however, there were no changes observed in critical nodes of insulin signalling. The present study provides evidence that supplementation with VA, a naturally produced trans-fat, has some positive effects on adipose tissue and did not exacerbate obesity-mediated metabolic abnormalities.

Vaccenic acid suppresses intestinal inflammation by increasing anandamide and related N-acylethanolamines in the JCR:LA-cp rat

Vaccenic acid (VA), the predominant ruminant-derived trans fat in the food chain, ameliorates hyperlipidemia, yet mechanisms remain elusive. We investigated whether VA could influence tissue endocannabinoids (ECs) by altering the availability of their biosynthetic precursor, arachidonic acid (AA), in membrane phospholipids (PLs). JCR:LA-cp rats were assigned to a control diet with or without VA (1% w/w), cis-9, trans-11 conjugated linoleic acid (CLA) (1% w/w) or VA+CLA (1% + 0.5% w/w) for 8 weeks. VA reduced the EC, 2-arachidonoylglycerol (2-AG), in the liver and visceral adipose tissue (VAT) relative to control diet (P < 0.001), but did not change AA in tissue PLs. There was no additive effect of combining VA+CLA on 2-AG relative to VA alone (P > 0.05). Interestingly, VA increased jejunal concentrations of anandamide and those of the noncannabinoid signaling molecules, oleoylethanolamide and palmitoylethanolamide, relative to control diet (P < 0.05). This was consistent with a lower jejunal protein abundance (but not activity) of their degrading enzyme, fatty acid amide hydrolase, as well as the mRNA expression of TNFα and interleukin 1β (P < 0.05). The ability of VA to reduce 2-AG in the liver and VAT provides a potential mechanistic explanation to alleviate ectopic lipid accumulation. The opposing regulation of ECs and other noncannabinoid lipid signaling molecules by VA suggests an activation of benefit via the EC system in the intestine.

Secoisolariciresinol Diglucoside and Cyanogenic Glycosides in Gluten-free Bread Fortified with Flaxseed Meal

Flaxseed (Linum usitatissimum L.) meal contains cyanogenic glycosides (CGs) and the lignan secoisolariciresinol diglucoside (1). Gluten-free (GF) doughs and baked goods were produced with added flaxseed meal (20%, w/w) then 1, and CGs were determined in fortified flour, dough, and bread with storage (0, 1, 2, and 4 weeks) at different temperatures (-18, 4, and 22-23 °C). 1 was present in flour, dough, and GF bread after baking. 1 was stable with extensive storage (up to 4 weeks) and was not affected by storage temperature. CGs in flaxseed meal and fortified GF samples were analyzed by 1H NMR of the cyanohydrins. Linamarin and/or linustatin were the primary CGs in both flaxseed meal and fortified flour. CGs decreased with storage in dough fortified with flaxseed meal or GF bread after baking. GF bakery food products fortified with flaxseed meal had reduced CGs but remained a good source of dietary 1.

Nomenclature of homodetic cyclic peptides produced from ribosomal precursors: an IUPAC Task Group interim report

In 2015, an International Union of Pure and Applied Chemistry (IUPAC) Task Group was formed to develop nomenclature recommendations for homodetic cyclic peptides produced from ribosomal precursors. Delegates of the 2015 International Conference on Circular Proteins (ICCP) were presented with the strengths and weaknesses of four published approaches to homodetic cyclic peptide nomenclature, and a summary of the ensuing discussion is presented here. This interim report presents a potentially novel suggestion—the use of Cahn‐Ingold‐Prelog rules to specify amino acid priority in homodetic peptides for consistent numbering. Indeed, this might be the first extension of the Cahn‐Ingold‐Prelog rules in five decades. The authors invite interested parties to contact the corresponding author with suggestions for the improvement of the proposed nomenclature; these ideas will be discussed and considered for inclusion in the final report.