Marianne O'Shea

Immunomodulatory properties of conjugated linoleic acid

In vitro studies of the use of immune cells and animal models demonstrate that conjugated linoleic acid (CLA), a lipid, modulates immune function. In addition, recent publications demonstrate that 2 active CLA isomers (ie, cis-9,trans-11 CLA and trans-10,cis-12 CLA) modulate immune function in humans. Aspects of both the innate and adaptive immune responses are affected by dietary CLA supplementation. CLA consists of a mixture of isomers, which reduced immune-induced wasting and enhanced ex vivo lymphocyte proliferation in broilers and decreased tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) production in rat models. In mice, ex vivo lymphocyte proliferation and IL-2 production were increased. Furthermore, evidence suggests that the cis-9,trans-11 and trans-10,cis-12 CLA isomers exert distinct effects on immune function. Specifically, these 2 isomers have differential effects on specific T cell populations and immunoglobulin subclasses in animal and human studies. Herein, a systematic review of the literature and relevant new data are presented with an aim to compare data and to present an overview covering the innate and adaptive components of the immune response that are regulated by CLA. In addition, potential mechanisms of action are discussed and the need for future studies on the immunomodulatory properties of CLA are outlined in detail. The understanding of the mechanism(s) by which CLA increases immune function will aid in the development of nutritionally based therapeutic applications to augment host resistance against infectious diseases and to treat immune imbalances, which result in inflammatory disorders, allergic reactions, or both.

Six months supplementation with conjugated linoleic acid induces regional-specific fat mass decreases in overweight and obese

Long-term supplementation with conjugated linoleic acid (CLA) reduces body fat mass (BFM) and increases or maintains lean body mass (LBM). However, the regional effect of CLA was not studied. The study aimed to evaluate the effect of CLA per region and safety in healthy, overweight and obese adults. A total of 118 subjects (BMI: 28-32 kg/m2) were included in a double blind, placebo-controlled trial. Subjects were randomised into two groups supplemented with either 3 x 4 g/d CLA or placebo for 6 months. CLA significantly decreased BFM at month 3 (Delta=- 0 x 9 %, P=0 x 016) and at month 6 (Delta=- 3 x 4 %, P=0 x 043) compared with placebo. The reduction in fat mass was located mostly in the legs (Delta=- 0 x 8 kg, P<0 x 001), and in women (Delta=-1 x 3 kg, P=0 x 046) with BMI >30 kg/m2 (Delta=-1 x 9 kg, P=0 x 011), compared with placebo. The waist-hip ratio decreased significantly (P=0 x 043) compared with placebo. LBM increased (Delta=+0 x 5 kg, P=0 x 049) within the CLA group. Bone mineral content was not affected (P=0 x 70). All changes were independent of diet and physical exercise. Safety parameters including blood lipids, inflammatory and diabetogenic markers remained within the normal range. Adverse events did not differ between the groups. It is concluded that supplementation with CLA in healthy, overweight and obese adults decreases BFM in specific regions and is well tolerated.

Activation of PPAR γ and α by punicic acid ameliorates glucose tolerance and suppresses obesity-related inflammation.

Objective: Peroxisome proliferator-activated receptor γ (PPAR γ) is the molecular target for thiazolidinediones (TZDs), a class of synthetic antidiabetic agents. However, the naturally occurring agonists of PPARs remain largely unknown. Punicic acid (PUA) is a conjugated linolenic acid isomer found in pomegrante. The objective of this study was to test the hypothesis that PUA activates PPAR γ and thereby ameliorates glucose homeostasis and obesity-related inflammation. Methods: The ability of PUA to modulate PPAR reporter activity was determined in 3T3-L1 pre-adipocytes. A cell-free assay was used to measure PUAs binding to the ligand-binding domain (LBD) of human PPAR γ. The preventive actions of PUA were investigated using genetically obese db/db mice and a model of diet-induced obesity in PPAR γ-expressing and tissue-specific PPAR γ null mice. Expression of PPAR α, γ, PPAR-responsive genes and TNF-α was measured in tissues controlling glucose homeostasis. Results: PUA caused a dose-dependent increase PPAR α and γ reporter activity in 3T3-L1 cells and bound although weakly to the LBD of human PPAR γ. Dietary PUA decreased fasting plasma glucose concentrations, improved the glucose-normalizing ability, suppressed NF-κB activation, TNF-α expression and upregulated PPAR α- and γ-responsive genes in skeletal muscle and adipose tissue. Loss of PPAR γ impaired the ability of dietary PUA to improve glucose homeostasis and suppress inflammation. Conclusions: Our studies demonstrate that PUA binds and robustly activates PPAR γ, increases PPAR γ-responsive gene expression and the loss of PPAR γ in immune cells impairs its ability to ameliorate diabetes and inflammation.

Effect of conjugated linoleic acid on body fat accretion in overweight or obese children

BACKGROUND Conjugated linoleic acid (CLA) is a supplemental dietary fatty acid that decreases fat mass accretion in young animals. OBJECTIVE The aim of this study was to determine CLAs efficacy with regard to change in fat and body mass index (BMI; in kg/m(2)) in children. DESIGN We conducted a 7 +/- 0.5-mo randomized, double-blind, placebo-controlled trial of CLA in 62 prepubertal children aged 6-10 y who were overweight or obese but otherwise healthy. The subjects were randomly assigned to receive 3 g/d of 80% CLA (50:50 cis-9,trans-11 and trans-10,cis-12 isomers) or placebo in chocolate milk. RESULTS Fifty-three subjects completed the trial (n = 28 in the CLA group, n = 25 in the placebo group). CLA attenuated the increase in BMI (0.5 +/- 0.8) compared with placebo (1.1 +/- 1.1) (P = 0.05). The percentage change in body fat measured by dual-energy X-ray absorptiometry was smaller (P = 0.001) in the CLA group (-0.5 +/- 2.1%) than in the placebo group (1.3 +/- 1.8%). The change in abdominal body fat as a percentage of total body weight was smaller (P = 0.02) in the CLA group (-0.09 +/- 0.9%) than in the placebo group (0.43 +/- 0.6%). There were no significant changes in plasma glucose, insulin, or LDL cholesterol between groups. Plasma HDL cholesterol decreased significantly more (P = 0.05) in the CLA group (-5.1 +/- 7.3 mg/dL) than in the placebo group (-0.7 +/- 8 mg/dL). Bone mineral accretion was lower (P = 0.04) in the CLA group (0.05 +/- 0.03 kg) than in the placebo group (0.07 +/- 0.03 kg). Reported gastrointestinal symptoms did not differ significantly between groups. CONCLUSIONS CLA supplementation for 7 +/- 0.5 mo decreased body fatness in 6-10-y-old children who were overweight or obese but did not improve plasma lipids or glucose and decreased HDL more than in the placebo group. Long-term investigation of the safety and efficacy of CLA supplementation in children is recommended.

Activation of PPARγ and δ by dietary punicic acid ameliorates intestinal inflammation in mice

The goal of the present study was to elucidate the mechanisms of immunoregulation by which dietary punicic acid (PUA) prevents or ameliorates experimental inflammatory bowel disease (IBD). The expression of PPARγ and δ, their responsive genes and pro-inflammatory cytokines was assayed in the colonic mucosa. Immune cell-specific PPARγ null, PPARδ knockout and wild-type mice were treated with PUA and challenged with 2·5 % dextran sodium sulphate (DSS). The prophylactic efficacy of PUA was examined in an IL-10(-/-) model of IBD. The effect of PUA on the regulatory T-cell (Treg) compartment was also examined in mice with experimental IBD. PUA ameliorated spontaneous pan-enteritis in IL-10(-/-) mice and DSS colitis, up-regulated Foxp3 expression in Treg and suppressed TNF-α, but the loss of functional PPARγ or δ impaired these anti-inflammatory effects. At the cellular level, the macrophage-specific deletion of PPARγ caused a complete abrogation of the protective effect of PUA, whereas the deletion of PPARδ or intestinal epithelial cell-specific PPARγ decreased its anti-inflammatory efficacy. We provide in vivo molecular evidence demonstrating that PUA ameliorates experimental IBD by regulating macrophage and T-cell function through PPARγ- and δ-dependent mechanisms.

In vitro antioxidant capacity and anti-inflammatory activity of seven common oats

Oats are gaining increasing scientific and public interest for their purported antioxidant-associated health benefits. Most reported studies focused on specific oat extracts or particular oat components, such as β-glucans, tocols (vitamin E), or avenanthramides. Studies on whole oats with respect to antioxidant and anti-inflammatory activities are still lacking. Here the antioxidant and anti-inflammatory activities from whole oat groats of seven common varieties were evaluated. All oat varieties had very similar oxygen radical absorption capacity compared with other whole grains. In an anti-inflammatory assay, oat variety CDC Dancer inhibited tumor necrosis factor-α induced nuclear factor-kappa B activation by 27.5% at 2 mg/ml, whereas variety Deiter showed 13.7% inhibition at a comparable dose. Avenanthramide levels did not correlate with the observed antioxidant and anti-inflammatory activities. Further investigations are needed to pinpoint the specific antioxidant and anti-inflammatory compounds, and potential synergistic and/or matrix effects that may help explain the mechanisms of oats anti-inflammatory actions.

Acute Effect of Oatmeal on Subjective Measures of Appetite and Satiety Compared to a Ready-to-Eat Breakfast Cereal: A Randomized Crossover Trial

Objective: The physicochemical properties of soluble oat fiber (β-glucan) affect viscosity-dependent mechanisms that influence satiety. The objective of this study was to compare the satiety impact of oatmeal with the most widely sold ready-to-eat breakfast cereal (RTEC) when either was consumed as a breakfast meal. Methods: Forty-eight healthy individuals ≥18 years of age were enrolled in a randomized crossover trial. Following an overnight fast, subjects consumed either oatmeal or RTEC in random order at least a week apart. The breakfasts were isocaloric and contained 363 kcal (250 kcal cereal, 113 kcal milk). Visual analogue scales measuring appetite and satiety were completed before breakfast and throughout the morning. The content and physicochemical properties of oat β-glucan were determined. Appetite and satiety responses were analyzed by area under the curve (AUC). Physicochemical properties were analyzed using t tests. Results: Oatmeal, higher in fiber and protein but lower in sugar than the RTEC, resulted in greater increase in fullness (AUC: p = 0.005 [120 minute: p = 0.0408, 180 minute: p = 0.0061, 240 minute: p = 0.0102]) and greater reduction in hunger (AUC: p = 0.0009 [120 minute: p = 0.0197, 180 minute: p = 0.0003, 240 minute: p = 0.0036]), desire to eat (AUC: p = 0.0002 [120 minute: p = 0.0168, 180 minute: p < 0.0001, 240 minute: p = 0.0022]), and prospective intake (AUC: p = 0.0012 [120 minute: p = 0.0058, 180 minute: p = 0.006, 240 minute: p = 0.0047]) compared to the RTEC. Oatmeal had higher β-glucan content, higher molecular weight (p < 0.0001), higher viscosity (p = 0.025), and larger hydration spheres (p = 0.0012) than the RTEC. Conclusion: Oatmeal improves appetite control and increases satiety. The effects may be attributed to the viscosity and hydration properties of its β-glucan content.

Instant Oatmeal Increases Satiety and Reduces Energy Intake Compared to a Ready-to-Eat Oat-Based Breakfast Cereal: A Randomized Crossover Trial

Background: Foods that enhance satiety can help consumers to resist environmental cues to eat and help adherence to calorie restriction. The objective of this study was to compare the effect of 2 oat-based breakfast cereals on appetite, satiety, and food intake. Methods: Forty-eight healthy individuals, 18 years of age or older, were enrolled in a randomized, crossover trial. Subjects consumed isocaloric servings of either oatmeal or an oat-based ready-to-eat breakfast cereal (RTEC) in random order at least a week apart. Visual analogue scales measuring appetite and satiety were completed before breakfast and throughout the morning. Lunch was served 4 hours after breakfast. The physicochemical properties of oat soluble fiber (β-glucan) were determined. Appetite and satiety responses were analyzed by area under the curve. Food intake and β-glucan properties were analyzed using t tests. Results: Oatmeal increased fullness (p = 0.001) and reduced hunger (p = 0.005), desire to eat (p = 0.001), and prospective intake (p = 0.006) more than the RTEC. Energy intake at lunch was lower after eating oatmeal compared to the RTEC (p = 0.012). Oatmeal had higher viscosity (p = 0.03), β-glucan content, molecular weight (p < 0.001), and radius of gyration (p < 0.001) than the RTEC. Conclusions: Oatmeal suppresses appetite, increases satiety, and reduces energy intake compared to the RTEC. The physicochemical properties of β-glucan and sufficient hydration of oats are important factors affecting satiety and subsequent energy intake.

Rapid quantitation of avenanthramides in oat-containing products by high-performance liquid chromatography coupled with triple quadrupole mass spectrometry (HPLC-TQMS)

Avenanthramides (AVNs) are a family of nitrogen-containing phenolic compounds produced in oat; AVN 2c, 2p, and 2f are the three major members. An LC-MS/MS method was developed, with the limit of detection (LOD) and the limit of quantitation (LOQ) being, respectively, 0.29ng/mL and 1.96ng/mL for AVN 2c, 0.24ng/mL and 0.60ng/mL for AVE 2p, and 0.42ng/mL and 2.2ng/mL for AVN 2f. The method was validated in oat-containing hot cereal and snack bar samples. The recovery of AVN 2c, 2p, and 2f from these two oat products was 95-113%, and the relative standard deviations ranged from 5% to 9%. This method was used to evaluate oat products and raw oat samples. The effects of location and variety on AVN composition were investigated. The method presented here provides a novel and rapid tool to quantitate the abundance of AVN 2c, 2p, and 2f in oat-containing products.