Maternal pea fiber supplementation to a high calorie diet in obese pregnancies protects male offspring from metabolic dysfunction in adulthood.

We investigated the influence of maternal yellow-pea fiber supplementation in obese pregnancies on offspring metabolic health in adulthood. Sixty newly-weaned female Sprague-Dawley rats were randomized to either a low-calorie control diet (CON) or high calorie obesogenic diet (HC) for 6-weeks. Obese animals were then fed either the HC diet alone or the HC diet supplemented with yellow-pea fiber (HC + FBR) for an additional 4-weeks prior to breeding and throughout gestation and lactation. On postnatal day (PND) 21, 1 male and 1 female offspring from each dam were weaned onto the CON diet until adulthood (PND 120) for metabolic phenotyping. Adult male, but not female, HC offspring demonstrated increased body weight and feed intake vs CON offspring, however no protection was offered by maternal FBR supplementation. HC male and female adult offspring demonstrated increased serum glucose and insulin resistance (HOMA-IR) compared with CON offspring. Maternal FBR supplementation improved glycemic control in male, but not female offspring. Compared with CON offspring, male offspring from HC dams demonstrated marked dyslipidemia (higher serum cholesterol, increased number of TG-rich lipoproteins, and smaller LDL particles) which was largely normalized in offspring from HC + FBR mothers. Male offspring born to obese mothers (HC) had higher hepatic TG, which tended to be lowered (p = 0.07) by maternal FBR supplementation.Supplementation of a maternal high calorie diet with yellow-pea fiber in prepregnancy and throughout gestation and lactation protects male offspring from metabolic dysfunction in the absence of any change in body weight status in adulthood.

Evaluating the Lipid-Lowering Effects of α-lipoic Acid Supplementation: A Systematic Review.

Dietary supplementation of α-lipoic acid, an 8-carbon organosulfur compound, has been widely reported to lower blood glucose concentration and/or improve insulin sensitivity in previous randomized controlled trials. Although animal model studies further report fairly consistent lipid lowering in both blood and tissue pools in response to α-lipoic acid supplementation, results from human studies are mixed. According to PRISMA guidelines, we conducted a systematic review of published randomized controlled studies (RCTs) to assess the efficacy of α-lipoic acid supplementation as a strategy to improve dyslipidemia, with a focus on serum lipid endpoints including TC, low density lipoprotein cholesterol (LDL-C), HDL-C, and TG. PubMed, EMBASE, Cochrane Evidence-Based Medicine Reviews, Proquest, Web of Science, and Scopus were searched to identify RCTs that reported the effects of α-lipoic acid on blood lipid concentrations from 1970 to 2017. We included RCTs reporting blood lipid responses in adults supplemented with oral α-lipoic acid versus a placebo or control for at least one month. Studies were reviewed and data were extracted by two independent study authors. Seventeen studies were deemed eligible for inclusion. Overall, mean percent changes in blood lipid endpoints in response to α-lipoic acid varied considerably between studies for total cholesterol (-10.5 to +13.9), low-density lipoprotein cholesterol (-19.67 to +9.06), high-density lipoprotein cholesterol (-12.5 to +29.20), and triglycerides (-38.57 to +17.0). Results of this systematic review suggest little consistent benefit on serum lipids in response to α-lipoic acid supplementation. Further well-controlled studies designed and powered to detect improvements in blood lipids in hypercholesterolemic individuals are warranted (PROSPERO registration number: CRD42018105933).

Metabolic effects of α-lipoic acid supplementation in pre-diabetics: a randomized, placebo-controlled pilot study.

Supplementation of health promoting nutraceuticals may be an effective adjunct strategy with other lifestyle and drug approaches to impede disease progression in prediabetic subjects. α-Lipoic acid, a naturally occurring short-chain fatty acid, has been extensively evaluated for its antioxidant and glycemic control properties but has rarely been investigated as a lipid-lowering strategy. We conducted a pilot study to examine the effects of α-lipoic acid supplementation on glycemic control and lipid profile in pre-diabetic, overweight/obese adults. The study was designed as a free-living, randomized, two-phase, placebo-controlled cross-over study with 12 pre-diabetic, dyslipidemic subjects. Eligible subjects completed two thirty-day phases (in random order) consisting of a placebo (600 mg cellulose per day) and α-lipoic acid treatment (600 mg day-1). Although no change (p < 0.05) in serum glucose was observed, α-lipoic acid-supplemented subjects demonstrated reduced fasting serum insulin (p = 0.04) and HOMA-IR (p = 0.07) compared with the placebo group. However, no change (p > 0.05) in serum lipids (including total cholesterol, LDL-C, HDL-C, triglycerides, LDL-C/HDL-C, and TC/HDL-C) were observed. Study results suggest that α-lipoic acid supplementation may be a useful strategy to improve insulin sensitivity in pre-diabetic subjects but is not effective in modulating serum lipids.

Maternal hypercholesterolemia enhances oxysterol concentration in mothers and newly weaned offspring but is attenuated by maternal phytosterol supplementation.

In hypercholesterolemic pregnancies, the maternal environment is characterized by excessive levels of atherogenic lipids that may increase cardiovascular disease risk in mothers and their offspring. We examined the influence of maternal hypercholesterolemia and phytosterol (PS) intervention on the concentration and metabolism of oxysterols, bioactive oxygenated cholesterol derivatives that regulate arterial health and lesion progression, in mothers and their newly weaned offspring. Twenty-one female apoE-/- mice were randomly assigned to three different diets throughout gestation and lactation: (1) chow, (2) high cholesterol (CH; 0.15%) and (3) CH with added PS (2%, CH/PS). At the end of the lactation period, mothers and pups were euthanized for serum and hepatic oxysterol analyses, hepatic transcriptional profiling of hepatic sterol regulatory targets and atherosclerosis. Hypercholesterolemic dams and their pups demonstrated increased (P˂.05) serum oxysterols [including 24 hydroxycholesterol (HC), 25HC, 27HC, 7αHC, 7ßHC and 7 ketocholesterol)] compared with the chow group that were normalized by maternal PS supplementation. Hepatic oxysterol concentrations followed a similar pattern of response in mothers but were not altered in newly weaned pups. Hepatic mRNA expression suggested a pattern of enhanced abca1/g1 high-density-lipoprotein-mediated efflux but a reduction in biliary abcg5/g8 export in both dams and their pups. Although arterial lesions were not apparent in newly weaned pups, CH dams demonstrated enhanced atherosclerosis that was reduced upon PS intervention. These results demonstrate that offspring from hypercholesterolemic pregnancies have enhanced circulating oxysterol concentrations and highlight the potential utility of PS as a lipid-lowering option during hypercholesterolemic pregnancies for which there are currently limited options.

Transcriptional control of enterohepatic lipid regulatory targets in response to early cholesterol and phytosterol exposure in apoE-/- mice.

OBJECTIVE: An excessive rise in blood lipids during pregnancy may promote metabolic dysfunction in adult progeny. We characterized how maternal phytosterol (PS) supplementation affected serum lipids and the expression of lipid-regulatory genes in the intestine and liver of newly-weaned apo-E deficient offspring from dams fed a chow diet supplemented with cholesterol (0.15%, CH) or cholesterol and PS (2%) (CH/PS) throughout pregnancy and lactation. RESULTS: Serum lipid concentrations and lipoprotein particle numbers were exacerbated in offspring from cholesterol-supplemented mothers but normalized to chow-fed levels in pups exposed to PS through the maternal diet during gestation and lactation. Compared with the CH pups, pups from PS-supplemented mothers demonstrated higher (p < 0.05) expression of the primary intestinal cholesterol transport protein (Niemann-Pick C1-like 1) and the rate-limiting enzyme in hepatic cholesterol synthesis (HMG-CoAr), suggestive of a compensatory response to restore cholesterol balance. Furthermore, pups from PS-supplemented mothers exhibited a coordinated downregulation (p < 0.05) of several genes regulating fatty acid synthesis including PGC1ß, SREBP1c, FAS, and ACC compared with the CH group. These results suggest that maternal PS supplementation during hypercholesterolemic pregnancies protects against aberrant lipid responses in newly-weaned offspring and results in differential regulation of cholesterol and lipid regulatory targets within the enterohepatic loop.

The Lipid-lowering Effects and Associated Mechanisms of Dietary Phytosterol Supplementation.

Phytosterols (PS) are plant-based structural analogous of mammalian cholesterol that have been shown to lower blood cholesterol concentrations by ~10%, although inter-individual response to PS supplementation due to subject-specific metabolic and genetic factors is evident. Recent work further suggests that PS may act as effective triglyceride (TG)-lowering agents with maximal TG reductions observed in hypertriglyceridemic subjects. Although PS have been demonstrated to interfere with cholesterol and perhaps TG absorption within the intestine, they also have the capacity to modulate the expression of lipid regulatory genes through liver X receptor (LXR) activation. Identification of single-nucleotide polymorphisms (SNP) in key cholesterol and TG regulating genes, in particular adenosine triphosphate binding cassette G8 (ABCG8) and apolipoprotein E (apoE) have provided insight into the potential of utilizing genomic identifiers as an indicator of PS responsiveness. While PS supplementation is deemed safe, expanding research into the atherogenic potential of oxidized phytosterols (oxyphytosterols) has emerged with their identification in arterial lesions. This review will highlight the lipid-lowering utility and associated mechanisms of PS and discuss novel applications and future research priorities for PS pertaining to in utero PS exposure for long-term cardiovascular disease risk protection and combination therapies with lipidlowering drugs.

Dietary Resistant Starch Supplementation Increases High-Density Lipoprotein Particle Number in Pigs Fed a Western Diet.

Resistant starch (RS) has been well characterized for its glycemic control properties; however, there is little consensus regarding the influence of RS on blood lipid concentrations and lipoprotein distribution and size. Therefore, this study aimed to characterize the effect of daily RS supplementation in a controlled capsule delivery on biomarkers of cardiovascular (blood lipids, lipoproteins) and diabetes (glucose, insulin) risk in a pig model. Twelve 8-week-old male Yorkshire pigs were placed on a synthetic Western diet and randomly divided into two groups (n = 6/group) for 30 days: (1) a placebo group supplemented with capsules containing unmodified pre-gelatinized potato starch (0 g/RS/day); and (2) an RS group supplemented with capsules containing resistant potato starch (10 g/RS/day). Serum lipids including total-cholesterol (C), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides did not differ (p > 0.05) between the RS and placebo groups. Although the total numbers of very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) particles were similar (p > 0.05) between the two groups, total high-density lipoprotein (HDL) particles were higher (+28%, p < 0.05) in the RS group compared with placebo, resulting from an increase (p < 0.05) in the small HDL subclass particles (+32%). Compared with the placebo group, RS supplementation lowered (p < 0.05) fasting serum glucose (-20%) and improved (p < 0.05) insulin resistance as estimated by Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) without a change in insulin. Additionally, total serum glucagon-like-peptide 1 (GLP-1) was higher (+141%, p < 0.05) following RS supplementation compared with placebo. This data suggests that in addition to the more well-characterized effect of RS intake in lowering blood glucose and improving insulin sensitivity, the consumption of RS may be beneficial in lipid management strategies by enhancing total HDL particle number.

Vitamin D supplementation affects the IGF system in men after acute exercise.

OBJECTIVE: Contradictory data between the Insulin-Like Growth Factor System (IGF) system and exercise may be due to alteration in IGF binding proteins. Vitamin D (D) deficiency has been related to muscle weakness and Insulin Like Growth Factor Binding Protein 3 (IGFBP3). A Vit. D and acute exercise merge is proposed to modify the IGF system. DESIGN: D insufficient and deficient men (39.0±8.6yo with serum D (25OH D) 20.0±7.7ng/mL) did 1h of stretching (ST), aerobic (AB), and resistance (RT) exercises, before and after 28d of 4000IU/d Vit. D3 (D, n=6) or Placebo (P, n=7). ST, a time/attention control visit, interchanged unreceptive movements. AB was moderate intensity treadmill walking. RT rotated moderate strength 50% 1-RM repetitions (15, 10) of squat, bench press, leg press, and lat pull down. Serum Total IGF1 (TIGF1), Insulin Like Growth Factor Binding Protein 1 (IGFBP1), and IGFBP3 were measured before (T1, fasting), immediately after (T2), and 2h post (T3) exercise. RESULTS: After ST, IGFBP3 was greater in the D group at T2 (2948, 2130ng/mL; p<0.03) and T3 (3087, 2212; p<0.02). During RT, TIGF1 decreased in the Placebo (P) group from T1 to T3 (151.4, 107.3ng/mL; p<0.05), while IGFBP1 increased in the D group from T1 to T3 (26.5, 96.2ng/mL; p<0.05). RT IGFBP3 was greater at T1, T2, and T3 in the D group (2932.5, 2110.7; p<0.03), (3163.9, 2392.5; p<0.04), and (3355.3, 2353.1; p<0.01). In AB, IGFBP3 was greater in the D group at T2 (3128.6, 2226.3.0; p<0.04) and T3 (2949.7, 2135.1; p<0.05). CONCLUSION: D supplementation amplified IGFBP3 after low or moderate activity which may increase the delivery of IGF1 to tissues. Resistance exercise with D not only increased IGFBP3 and IGFBP1 levels but also conserved TIGF1 levels, possibly shifting the IGF system for enriched muscle well-being.

Complementary Cholesterol-Lowering Response of a Phytosterol/α-Lipoic Acid Combination in Obese Zucker Rats.

To investigate the cholesterol-lowering effectiveness of a phytosterol/α-lipoic acid (PS/αLA) therapy, thirty-two male Zucker rats were randomly assigned to 1 of 4 diets for 30 days: (i) high fat diet (HF, 40% energy from fat); (ii) HF diet supplemented with 3% phytosterols; (iii) HF diet supplemented with 0.25% αLA; or (iv) HF diet supplemented with PS (3%) and αLA (0.25%, PS/αLA). Compared with the HF diet, combination PS/αLA proved more effective in reducing non-HDL cholesterol (-55%) than either the PS (-24%) or the αLA (-25%) therapies alone. PS supplementation did not affect LDL particle number, however, αLA supplementation reduced LDL particle number when supplemented alone (-47%) or in combination with PS (-54%). Compared with the HF-fed animals, evidence of increased HDL-particle number was evident in all treatment groups to a similar extent (21-22%). PS-mediated interruption of intestinal cholesterol absorption was evident by increased fecal cholesterol loss (+52%) and compensatory increase in HMG-CoA reductase mRNA (1.6 fold of HF), however, αLA supplementation did not affect fecal cholesterol loss. Hepatic mRNA and protein expression patterns suggested that αLA modulated multiple aspects of cholesterol homeostasis including reduced synthesis (HMG-CoA reductase mRNA, 0.7 fold of HF), reduced bile acid synthesis (CYP7a1 expression, 0.17 of HF), and increased cholesterol clearance (reduced PCSK9 mRNA, 0.5 fold of HF; increased LDLr protein, 2 fold of HF). Taken together, this data suggests that PS and αLA work through unique and complementary mechanisms to provide a superior and more comprehensive cholesterol lowering response than either therapy alone.

Maternal Phytosterol Supplementation during Pregnancy and Lactation Modulates Lipid and Lipoprotein Response in Offspring of apoE-Deficient Mice.

BACKGROUND: In utero exposure to excessive cholesterol has been shown to increase fetal plasma cholesterol concentration and predispose adult offspring to cardiovascular disease (CVD) risk. Because lipid-lowering drugs are contraindicated during pregnancy, natural cholesterol-lowering compounds may be a safe and effective alternative to reduce CVD risk in offspring born to hypercholesterolemic mothers. OBJECTIVE: This study used the hypercholesterolemic apolipoprotein E-deficient (apoE(-/-)) mouse model to test the hypothesis that mothers supplemented with phytosterols during gestation and lactation would produce offspring with a more favorable lipid profile than offspring from unsupplemented mothers, despite having a genetic predisposition toward hypercholesterolemia. METHODS: Sixteen female apoE(-/-) mice were randomly assigned to 2 diets fed throughout the gestation and lactation periods: a cholesterol-enriched diet (CH) (0.15%) or the cholesterol-enriched diet supplemented with phytosterols (CH/PS) (2%). Serum lipids and lipoproteins were measured by enzyme assay and nuclear magnetic resonance spectroscopy, respectively, and liver cholesterol was analyzed by GC. RESULTS: Compared with the CH-fed dams at the end of lactation, phytosterol-supplemented dams displayed lower (P < 0.05) serum total cholesterol (-55%), non-HDL cholesterol (-56%), and LDL cholesterol (-47%), but no change (P > 0.05) in HDL cholesterol and triacylglycerol (TG) concentrations. Pups from phytosterol-fed dams demonstrated lower (P < 0.05) total cholesterol (-25%), non-HDL cholesterol (-25%), LDL cholesterol (-47%), and TGs (-41%), without any change (P > 0.05) in HDL cholesterol compared with pups from CH-fed dams. Furthermore, compared with pups from CH-fed dams, pups from phytosterol-supplemented dams displayed a lower (P < 0.05) number of total LDL particles (-34%), VLDL particles (-31%), and HDL particles (-30%). CONCLUSION: Our results in apoE(-/-) mice suggest that even under strong genetic predisposition to hypercholesterolemia, pups born to mothers supplemented with phytosterols during gestation and lactation exhibit favorable liver and serum lipid responses compared with pups from unsupplemented mothers.

Alpha-lipoic acid supplementation reduces mTORC1 signaling in skeletal muscle from high fat fed, obese Zucker rats.

The mammalian target of rapamycin (mTOR) signaling pathway is hyperactive in liver, adipose and skeletal muscle tissues of obese rodents. Alpha-lipoic acid (αLA) has been well accepted as a weight-loss treatment, though there are limited studies on its effect on mTOR signaling in high-fat fed, obese rodents. Therefore, the goal of this study was to determine mTOR signaling and oxidative protein alterations in skeletal muscle of high-fat fed, obese rats after αLA supplementation. Phosphorylation of the mTOR substrate, eukaryotic initiation factor (eIF) 4E-binding protein 1 (4E-BP1) and eIF4B were significantly reduced (p < 0.05) in muscle from αLA supplemented rats. Activation of AMP-activated protein kinase (AMPK), an mTOR inhibitory kinase, was higher (p < 0.05) in the αLA group. Protein expression of markers of oxidative metabolism, acetyl CoA carboxylase (ACC), cytochrome c oxidase IV (COX IV), peroxisome proliferator-activated receptor (PPAR), and PPAR gamma coactivator 1-alpha (PGC-1α) were significantly higher (p < 0.05) after αLA supplementation compared to non-supplemented group. Our findings show that αLA supplementation limits the negative ramifications of consuming a high fat diet on skeletal muscle markers of oxidative metabolism and mTORC1 signaling.

Alpha-lipoic acid reduces LDL-particle number and PCSK9 concentrations in high-fat fed obese Zucker rats.

We characterized the hypolipidemic effects of alpha-lipoic acid (LA, R-form) and examined the associated molecular mechanisms in a high fat fed Zucker rat model. Rats (n = 8) were assigned to a high fat (HF) diet or the HF diet with 0.25% LA (HF-LA) for 30 days and pair fed to remove confounding effects associated with the anorectic properties of LA. Compared with the HF controls, the HF-LA group was protected against diet-induced obesity (102.5±3.1 vs. 121.5±3.6,% change BW) and hypercholesterolemia with a reduction in total-C (-21%), non-HDL-C (-25%), LDL-C (-16%), and total LDL particle number (-46%) and an increase in total HDL particles (∼22%). This cholesterol-lowering response was associated with a reduction in plasma PCSK9 concentration (-70%) and an increase in hepatic LDLr receptor protein abundance (2 fold of HF). Compared with the HF-fed animals, livers of LA-supplemented animals were protected against TG accumulation (-46%), likely through multiple mechanisms including: a suppressed lipogenic response (down-regulation of hepatic acetyl-CoA carboxylase and fatty acid synthase expression); enhanced hepatic fat oxidation (increased carnitine palmitoyltransferase Iα expression); and enhanced VLDL export (increased hepatic diacylglycerol acyltransferase and microsomal triglyceride transfer protein expression and elevated plasma VLDL particle number). Study results also support an enhanced fatty acid uptake (2.8 fold increase in total lipase activity) and oxidation (increased CPT1ß protein abundance) in muscle tissue in LA-supplemented animals compared with the HF group. In summary, in the absence of a change in caloric intake, LA was effective in protecting against hypercholesterolemia and hepatic fat accumulation under conditions of strong genetic and dietary predisposition toward obesity and dyslipidemia.

Phytosterols protect against diet-induced hypertriglyceridemia in Syrian golden hamsters.

BACKGROUND: In addition to lowering LDL-C, emerging data suggests that phytosterols (PS) may reduce blood triglycerides (TG), however, the underlying mechanisms are not known. METHODS: We examined the TG-lowering mechanisms of dietary PS in Syrian golden hamsters randomly assigned to a high fat (HF) diet or the HF diet supplemented with PS (2%) for 6 weeks (n = 12/group). An additional subset of animals (n = 12) was provided the HF diet supplemented with ezetimibe (EZ, 0.002%) as a positive control as it is a cholesterol-lowering agent with known TG-lowering properties. RESULTS: In confirmation of diet formulation and compound delivery, both the PS and EZ treatments lowered (p < 0.05) intestinal cholesterol absorption (24 and 31%, respectively), blood non-HDL cholesterol (61 and 66%, respectively), and hepatic cholesterol (45 and 55%, respectively) compared with the HF-fed animals. Blood TG concentrations were lower (p < 0.05) in the PS (49%) and EZ (68%)-treated animals compared with the HF group. The TG-lowering response in the PS-supplemented group was associated with reduced (p < 0.05) intestinal SREBP1c mRNA (0.45 fold of HF), hepatic PPARα mRNA (0.73 fold of HF), hepatic FAS protein abundance (0.68 fold of HD), and de novo lipogenesis (44%) compared with the HF group. Similarly, lipogenesis was lower in the EZ-treated animals, albeit through a reduction in the hepatic protein abundance of ACC (0.47 fold of HF). CONCLUSIONS: Study results suggest that dietary PS are protective against diet-induced hypertriglyceridemia, likely through multiple mechanisms that involve modulation of intestinal fatty acid metabolism and a reduction in hepatic lipogenesis.

Consumption of wheat bran modified by autoclaving reduces fat mass in hamsters.

PURPOSE: To investigate the effect that wheat bran modified by autoclaving (MWB) had on reducing fat accumulation in hamsters fed a hypercholesterolemia- and obesity-inducing diet. METHODS: Male hamsters (n = 45) were randomized into 3 groups and fed a hypercholesterolemia- and obesity-inducing diet with or without 10% standard wheat bran or MWB for 28 days. Our outcome measures included body composition measured by DXA, oxygen consumption and plasma lipids and glucose concentrations. RESULTS: Animals fed the MWB diet had lower % fat mass (49.8 vs. 53.4%; p = 0.02) and higher % lean body mass (47.2 vs. 44.1%; p = 0.02) compared with controls despite no differences in food intake or weight gain. Additionally, plasma glucose tended to be lower (6.9 vs. 8.5 mmol/l; p < 0.08) in the MWB animals compared with controls. CONCLUSIONS: Our data suggest that the compositional changes in autoclaved wheat bran, specifically solubility of phenolic antioxidants and fiber, may have contributed to the lower fat accumulation in our animals. Further study is needed to determine whether the exact mechanism involved increased lipolysis and energy utilization from adipose.

Fatty acid ethanolamides modulate CD36-mRNA through dietary fatty acid manipulation in Syrian Golden hamsters.

Fatty acids convert to fatty acid ethanolamides which associate with lipid signalling, fat oxidation, and energy balance; however, the extent to which dietary fatty acids manipulation can impact such control processes through fatty acid ethanolamides-related mechanisms remains understudied. The objective was to examine the impact of diets containing 6% corn oil, high oleic canola oil, docosahexaenoic acid + high oleic canola oil, and fish oil on plasma and organ levels of fatty acid ethanolamides, peroxisome proliferator-activated receptor-α regulatory targets, and lipid metabolism in Syrian Golden hamsters. After 29 days, in plasma, animals that were fed fish oil showed greater (p < 0.05) oleoylethanolamide and lower (p < 0.05) arachidonoylethanolamide and palmitoylethanolamide levels compared with other groups, while animals fed canola oil showed higher (p < 0.05) oleoylethanolamide levels in proximal intestine and liver than groups that were fed coin oil and fish oil. The canola oil group showed elevated (p < 0.01) fat oxidation (%) and over 3.0-fold higher (p < 0.05) hepatic-CD36 expression compared with the corn oil group. Hepatic-lipogenesis was lower (p < 0.05) in hamsters that were fed DHA-canola oil compared with the corn oil group. To conclude, dietary fatty acids produced shifts in plasma and organ levels of arachidonoylethanolamide, oleoylethanolamide, and palmitoylethanolamid, which were accompanied by changes in gene expression, lipogenesis, and energy expenditure, suggesting mechanisms through which dietary fatty acids influence disease risk.

Dietary oils and FADS1-FADS2 genetic variants modulate [13C]α-linolenic acid metabolism and plasma fatty acid composition.

BACKGROUND: Desaturation of dietary α-linolenic acid (ALA) to omega-3 (n-3) long-chain fatty acids (FAs) is mediated through FA desaturases (FADS1-FADS2) and may be influenced by dietary FA composition. OBJECTIVE: We investigated the effects of diets enriched in flaxseed oil (FXCO) or high-oleic acid canola oil (HOCO) compared with a Western diet (WD) and FADS1-FADS2 single nucleotide polymorphisms (SNPs) on plasma FAs and [U-(13)C]ALA metabolism. DESIGN: In a randomized crossover design, 36 hyperlipidemic subjects consumed 3 isoenergetic diets enriched in FXCO (20.6 g ALA/d), HOCO (2.4 g ALA/d), or WD (1.3 g ALA/d) for 4 wk. On day 27, blood was sampled 0, 24, and 48 h after the subjects (n = 26) consumed 45 mg [U-(13)C]ALA. The subjects were genotyped for 4 FADS SNPs. RESULTS: FXCO increased (P < 0.001) plasma ALA, EPA, and docosapentaenoic acid (DPA), with no change in DHA compared with the HOCO or WD diets. At 24 and 48 h, [U-(13)C]ALA recovered as plasma [(13)C]EPA and [(13)C]DPA were lower (P < 0.001) after the FXCO diet than after the HOCO and WD diets. No change in [(13)C]DHA was observed between diets. Minor allele homozygotes of rs174545, rs174583, rs174561, and rs174537 had lower (P < 0.05) plasma EPA, arachidonic acid (AA), EPA/ALA, and AA/linoleic acid compositions and lower (P < 0.05) plasma [(13)C]EPA enrichment at 24 and 48 h in comparison with carriers of the major allele after all diets. SNPs were not associated with plasma composition of DHA or [(13)C]DHA enrichment. CONCLUSION: An increase in ALA intake resulting in increased plasma EPA composition may be cardioprotective, especially in minor allele homozygotes. This trial was registered at www.clinicaltrials.gov as NCT00927199.

Evidence for using alpha-lipoic acid in reducing lipoprotein and inflammatory related atherosclerotic risk.

Alpha lipoic acid (α-LA) is a potent biological antioxidant that is found naturally in the human body at very low concentrations, primarily in the mitochondria. However, synthetic α-LA is commercially available as a nutritional supplement and has been shown to be effective at ameliorating symptoms in diseases with an underlying oxidative stress component. High blood cholesterol is a major cardiovascular disease (CVD) risk factor and is responsive to diet and lifestyle modifications. In addition to high blood cholesterol, there is increasing evidence that supports the independent role of oxidized lipids and lipoproteins, chiefly oxidized low-density lipoproteins (Ox-LDL), in the development of CVD. Lowering total blood cholesterol (TC), LDL cholesterol (LDL-C), and triglycerides (TG) and raising high-density lipoprotein cholesterol (HDL-C) levels is the most desirable metabolic state for maximum protection against CVD, but can be difficult to achieve through diet and exercise alone. With emerging evidence of reduced LDL-C and TG, increased HDL-C, and blunting of oxidative susceptibility of lipoproteins by α-LA, its use alone or in combination with other dietary supplements may be an effective strategy to modulate multiple metabolic targets of oxidative stress and cholesterol metabolism to reduce CVD risk. This review examines the current evidence for the use of α-LA in CVD risk reduction and identifies the remaining gaps that must be addressed in this area of research.

Regulatory approval of plant sterols in Canada: implications for health care and clinical practice.

Health Canada's recent approval of plant sterols as food ingredients to decrease low-density lipoprotein cholesterol (LDL-C) is believed to be a significant step toward improving Canadians' cardiovascular health and reducing the economic burden of heart disease. When dyslipidemic patients consume plant sterols at a recommended daily dose of 2 g, they can reduce LDL-C by 10% to 15%, with no deleterious effects on high-density lipoprotein cholesterol. A 10% LDL-C reduction in response to plant sterol consumption is projected to reduce heart disease risk by 25%. Because they are available without a prescription, plant sterols are an option for dietitians who wish to provide cholesterol-lowering guidance beyond traditional dietary advice (i.e., lowering saturated fat intake and restricting dietary cholesterol). In addition, plant sterols can be used in combination with a statin or when statin use is contraindicated, and they have recently emerged as a potentially valuable triglyceride-lowering option. However, the projected improvement in public health and health care savings will be realized only if impediments to daily use are removed. One such impediment is the higher cost of fortified food products, such as yogurt and margarine. If the cost of plant sterol food products is to decline, cost-effective sources must be investigated and a larger range of foods containing plant sterols must be made available.

Consumption of plant sterols reduces plasma and hepatic triglycerides and modulates the expression of lipid regulatory genes and de novo lipogenesis in C57BL/6J mice.

To investigate emerging clinical data suggesting a triglyceride (TAG)-lowering response to plant sterol (PS) therapy, we characterized changes in TAG metabolism in 16 C57BL/6J mice fed a basal control diet (CON) or the CON diet supplemented with 2% PS for 6 wk. PS consumption reduced (p<0.05) plasma (-28%) and hepatic (-30%) TAG concentrations compared with CON mice. PS consumption increased (p<0.05) hepatic lipogenic gene expression (sterol-regulatory-element-binding protein 1c, 2.4-fold of CON; fatty acid synthase, 6.5-fold of CON) and de novo lipogenesis (4.51+/-0.72 versus 2.82+/-0.61%/day) compared with CON. PS consumption increased (p<0.05) fecal palmitate and stearate excretion and reduced body weight gain compared with CON mice. Although no change in the transcription of intestinal fatty acid absorptive genes was observed, peroxisome proliferator-activated receptor alpha mRNA was reduced (p<0.05, 2.0-fold of CON) in the PS-fed mice. In conclusion, PS-fed C57BL/6J mice showed pronounced reductions in plasma and hepatic TAG concentrations despite increases in hepatic lipogenic gene expression and de novo lipogenesis. Interference with intestinal fatty acid/TAG metabolism as suggested by increased fecal fatty acid loss and reduced weight gain may be associated with the TAG-lowering response to PS consumption.

Nutrient utilisation and intestinal fermentation are differentially affected by the consumption of resistant starch varieties and conventional fibres in pigs.

This study examined the influence of different resistant starch (RS) varieties and conventional fibres on the efficiency of nutrient utilisation and intestinal fermentation in pigs. Thirty-six pigs (30 kg) were fed poultry meal-based diets supplemented with 10 % granular resistant corn starch (GCS), granular resistant potato starch (GPS), retrograded resistant corn starch (RCS), guar gum (GG) or cellulose for 36 d according to a completely randomised block design. Distal ileal and total tract recoveries were similar (P>0.05) among the RS varieties. Distal ileal starch recovery was higher (P < 0.05) in pigs consuming the RS diets (27-42 %) as compared with the control group (0.64 %). Consumption of GCS reduced (P < 0.05) apparent total tract digestibility and whole-body retention of crude protein in comparison with the control group. Consumption of GPS reduced (P < 0.05) total tract Ca digestibility and whole-body retention of Ca and P compared with the control group. However, consumption of RCS increased (P < 0.05) total tract Ca digestibility compared with the control group. Caecal butyrate concentration was increased (P < 0.05) following consumption of RCS and GG in comparison with the control group. Consumption of all the RS varieties reduced (P < 0.05) caecal indole concentrations compared with the control. Caecal butyrate concentrations were positively correlated (P < 0.05; r 0.63-0.83) with thermal properties among the RS varieties. We conclude that nutrient utilisation and intestinal fermentation are differentially affected by the consumption of different RS varieties and types of fibres. Thermal properties associated with different RS varieties may be useful markers for developing RS varieties with specific functionality.