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Dietetics, Nutrition and Biological Sciences

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Author: search.filters.author.Gow, Iain F.

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    Effects of oat β-glucan consumption at breakfast on ad libitum eating, appetite, glycemia, insulinemia and GLP-1 concentrations in healthy subjects.
    (2018-06-18) Zaremba, Suzanne; Gow, Iain F.; Drummond, Sandra; McCluskey, Jane T.; Steinert, Robert E.
    There is evidence that oat β-glucan lowers appetite and ad libitum eating; however, not all studies are consistent, and the underpinning mechanisms are not entirely understood. We investigated the effects of 4 g high molecular weight (MW) oat β-glucan on ad libitum eating, subjective appetite, glycemia, insulinemia and plasma GLP-1 responses in 33 normal-weight subjects (22 female/11 male, mean age (y): 26.9 ± 1.0, BMI (kg/m ): 23.5 ± 0.4). The study followed a randomised double-blind, cross-over design with subjects fed two test breakfasts with and without oat β-glucan followed by an ad libitum test meal on two different days. Blood samples and ratings for subjective appetite were collected postprandially at regular time intervals. Oat β-glucan increased feelings of fullness (p = 0.048) and satiety (p = 0.034), but did not affect energy and amount eaten at the ad libitum test meal. There was a treatment by time interaction for plasma GLP-1, plasma insulin and blood glucose. GLP-1 was significantly reduced at 90 min (p = 0.021), blood glucose at 30 min (p = 0.008) and plasma insulin at 30 and 60 min (p = 0.002 and 0.017, respectively) following the oat β-glucan breakfast when compared with the control breakfast. Four grams of high MW oat β-glucan lowers appetite but not ad libitum eating and beneficially modulates postprandial glycaemia, it does however, not increase plasma GLP-1 secretion. [Abstract copyright: Copyright © 2018 Elsevier Ltd. All rights reserved.]
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    Physiological levels of soy isoflavones reduce proliferation and promote apoptosis in the ER_-positive breast cancer cell line MDA-MB-231
    (Cambridge University Press, 2012-04) Wallace, J.; Warnock, Mary; Gow, Iain F.
    Dietary soy, particularly the high levels consumed as part of traditional Eastern-Asian diets, may be protective against certain subtypes of breast cancer(1). This effect is partly related its high isoflavone phytoestrogen content (genistein and daidzein). However much in vitro evidence suggests a contradictory, growth promoting impact of physiological (serum) levels of isoflavones in oestrogen receptor alpha positive (ERa+) breast cancer cell lines(2). This has led to the contraindication of isoflavone supplement use in post menopausal breast cancer survivors. The inconsistency between epidemiological and in vitro evidence may relate to the relative expression levels of ERa and its counterpart ERb. Unlike in cell lines predominantly expressing ERa, the proliferation of ERb-dominant cell lines can be inhibited by concentrations of genistein as low as 1 nM(3,4). This information is relevant as the ERa - /b+ subgroup represent approximately 18% of all breast tumours(5) but the beta-receptor is not routinely tested for upon diagnosis. We assessed the impact of physiologically relevant concentrations (serum levels achievable through diet: 0.01nM to 31.6 mM) of the soy isoflavones genistein and daidzein on proliferation (MTT assay) and apoptosis with the Annexin V-Cy32 Apoptosis Detection Kit and DAPI staining/Nuclear Area Factor (NAF) calculation in the ERa - /b+ breast cancer cell line MDA-MB-231. Low doses of genistein or daidzein (- 0.01 nM) inhibited MDA-MB-231 proliferation by around 20%, although this frequently failed to achieve statistical significance. The highest concentrations used (31.6 mM) resulted in a dramatic decrease in percent proliferation compared with a vehicle only control (meanSD : 48.512.6, p = 0.004 and 48.413.1, p<0.001 for genistein and daidzein respectively; n = 3). 17b-oestradiol (E2; the major circulating oestrogen) also slightly reduced proliferation at its pre- and post-menopausal serum concentrations (1nM and 1 pM respectively). This reduction in proliferation was associated with an observed increase in cell death at 10 and 31.6 mM genistein and daidzein, which was at least partly explained by an increase in the percentage of apoptotic cells. While the combination of E2 and isoflavones failed to show any synergistic growth inhibitory, or pro-apoptotic effects, some inhibition of proliferation was still documented. This implies that the growth inhibitory effects of genistein, daidzein and E2 may not be regulated by the same mechanisms. However, more importantly, the apoptotic cell death observed with soy isoflavone treatment was not abrogated by the addition of physiological E2 concentrations. Overall, our data suggests that at concentrations achievable through the diet ( 10 mM) soy isoflavones may be potentially beneficial as chemotherapeutic agents against ERa - /b+ breast cancers, through their ability to reduce proliferation and promote apoptosis, even in the presence of physiological E2 levels. Routine determination of the expression levels of ERb in addition to ERa in breast cancer would be an invaluable biomarker to indicate the potential efficacy of this cheap and readily available treatment, and indicates a possible pharmacological target. 1. Wu AH, Yu MC, Tseng CC, Pike MC (2008) Brit J Cancer 98:9-14. 2. Hwang CS, Kwak HS, Lim HJ, et al. (2006) J Steroid Biochem Mol Bio 101:246-53. 3. Rajah TT, Du N, Drews N, Cohn R (2009) Pharmacology 84:68-73. 4. Kang X, Jin S, Zhang Q (2009) J Food Sci 74:H237-H242. 5. Skliris GP, Leygue E, Watson PH, Murphy LC (2008) J Steroid Biochem Mol Bio 109:1-10.
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    The effect of 17-β oestradiol, resveratrol, and genistein on Na+/H+ exchange in breast cancer cells lines
    (Cambridge University Press, 2012-03) Wallace, J.; Foy, Daniel; Yousuf, Huma; Warnock, Mary; Gow, Iain F.
    The tumour environment is more acidic than normal (pH 6.8 vs 7.3)(1), and this may aid tumour progression or affect the uptake of drugs. The extracellular pH may be partly-regulated by cellular sodium/hydrogen exchangers (NHEs), and NHE activation may in turn be regulated by hormones such as oestradiol(2). Some breast cancers possess receptors for oestradiol, and stimulation or blockade of these receptors may modulate the cell's ability to regulate pH. We studied this by investigating the effect of oestradiol on the ability of breast cancer cell lines to regulate pH by NHE. We used MCF-7 (expresses oestrogen receptors a and b) and MDA-MB-231 (expresses only oestrogen receptor b) cell lines. Given the interaction of phytoestrogens with the oestrogen receptor(3), we also looked at the effect of resveratrol (RSV) or genistein (Gen). MCF-7 and MDA-MB-231 cells were used either as suspensions, or on coverslips, in the absence of added oestradiol. Cells were loaded with H+ -sensitive fluorescent probe BCECF, then washed to remove excess dye. Suspended cells were allowed to adhere to the glass bottom of the 35mm perfusion chamber, coverslips with cells were added to the chamber directly. Cells were perfused (1 ml/min) at 37C with HEPES-buffed Tyrode (pH 7.4) to which drugs were added as required. Acidification was induced by the NH4Cl pre-pulse technique, recovery was achieved by returning to normal Tyrode. Cells were illuminated by alternating wavelengths of 440 and 503 nm light (2 Hz sample rate), and fluorescent light (>535 nm) was captured by a CCD camera. The fluorescence ratios are directly proportional to the H+ concentration. Drugs were added directly to the Tyrode, and since RSV and Gen were dissolved in DMSO, DMSO (0.01% final) was added to the pre-perfusing Tyrode in those experiments, and used as a control in the absence of drugs. Results are mean ratio valuesSEM or slopes of rate of change of ratio/minSEM for three separate experimental days, except for the DMSO controls where n = 6. Differences were assessed by Student's paired or unpaired t tests. A brief (4 min) exposure of breast cancer cells to NH4Cl (20mM) caused a transient alkalisation (decrease in 440/503 ratio, i.e. decrease in [H + ]i) followed by an acidification and recovery after ammonium removal. In MDA cells, addition of 17b-oestradiol (E2; 1 pM final concentration) had no effect on the rate of recovery from acidification (Control: - 3.44E-041.34E-04; MDA: - 2.26E-040.69E-04). In MCF-7 cells, perfusing with Tyrode containing 1 pM E2 significantly increased the rate of recovery from acidification (Control: - 1.61E-040.22E-04; MCF-7: - 3.66E- 040.18E-04; p<0.05). Inclusion of DMSO alone in the medium perfusing MCF-7 cells significantly increased the basal ratio compared with cells in Tyrode alone (Control: 1.240.18; DMSO: 1.710.09; p<0.05), and also increased the rate of recovery (Control: - 1.61E- 040.22E-04; DMSO: - 3.97E-040.52E-04; p<0.02). Inclusion of RSV (1 mM) in the perfusate with MCF-7 cells also caused an increase in the rate of recovery relative to the DMSO-only control (DMSO: - 3.97E-040.52E-04; RSV: - 6.84E-040.56E-04; p<0.02). Gen (1 mM) had no significant effects in MCF-7 cells, though all three recovery rates were numerically higher than the DMSO control. In summary, we have shown that E2 and RSV at physiological levels can increase the rate of recovery from acidification in a breast cancer cell line expressing oestrogen receptors a and b. Given the potential importance of cytosolic and extracellular pH regulation in both the ability of cytotoxic drugs to cross the membrane or the cell to proliferate, the physiological effects of foodborne phytohormones on pathways regulating cell pH clearly requires further investigation. 1. Raghunand N, He X, van Sluis R, Mahoney B, Baggett B, Taylor CW, Paine-Murrieta G, Roe D, Bhujwalla ZM, Gillies RJ (1999) Br J Cancer 80: 1005-1011. 2. Kilic A, Jaradov S, and Karmazyn M (2009) J Mol Cell Cardiol 46:360-36. 3. Hwang CS, Kwak HS, Lim HJ, Lee SH, Kang YS, Choe TB, Hur HG & Han KO (2006) J Steroid Biochem Mol Biol 101: 246-253.
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    Physiological levels of soy isoflavones inhibit the growth of oestrogen receptor β-positive but not α-positive breast cancer cells
    (Society for Endocrinology, 2012-03) Wallace, J.; Gow, Iain F.; Warnock, Mary
    The biphasic effect of soy isoflavones (genistein and daidzein) on oestrogen receptor (ER)α+ breast cancer cell proliferation is well documented, with concentrations of ≤10 µM promoting proliferation, and growth inhibitory and apoptotic effects seen at concentrations ≥10 µM. However genistein concentrations as low as 1nM may inhibit the proliferation of some ERα-/β+ cells. This is at odds with epidemiological evidence which suggests that high serum levels of soy isoflavones (around 1 µM) are associated with reduced breast cancer risk, particularly for ERα+ and premenopausal cancers. It is possible that interactions with endogenous oestrogens may be behind this discrepancy. The object here was to investigate combinations of genistein and daidzein at levels achievable in the serum through diet alone, at pre- and postmenopausal oestrogen levels, on breast cancer cell proliferation and apoptosis. ERα+ MCF7 and ERα-/β+ MDA-MB-231 cells were treated with genistein, daidzein and 17β-oestradiol at physiologically relevant levels. Physiological levels of soy isoflavones promoted but not inhibit the proliferation of MCF7 cells, whilst simultaneously inducing low level apoptosis. E2 acted synergistically on proliferation with the isoflavones, increasing proliferation further, but did not impact upon their apoptotic capacity. All concentrations of genistein and daidzein resulted in a slight reduction in MDA-MB-231 proliferation, with this dropping dramatically at the highest dose of 31.6 µM. Overall this suggests that physiological levels of isoflavones may be of benefit as chemotherapeutic agents against ERα-/β+ breast cancer. However they are not capable of reducing the proliferation of ERα+ MCF7 cells, or inhibiting oestrogenic promotion of growth. Other factors must be involved, not reflected by this model. Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported. Funding: No specific grant from any funding agency in the public, commercial or not-for-profit sector.
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    Pharmacological & Physiological Characterisation of the Rat Mammary Artery at Different Stages of Reproduction: Final Report to the Scottish Government Rural and Environment Research and Analysis Directorate (RERAD).
    (Scottish Government, 2009) Gow, Iain F.
    The overarching-aim of the project was to assess the responsiveness of the rat mammary artery during different stages of the reproductive cycle. This has implications for not only normal physiology, but also heart disease, since women who undergo coronary artery bypass surgery using mammary arteries as the conduit and who have breastfed their offspring have a significantly better prognosis that those who have never breastfed.
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    Resveratrol-induced relaxation of the isolated rabbit mammary artery is not attenuated by 17-oestradiol
    (2011) Carson, T.; Gill, Jan; Gow, Iain F.; Johnson, S.; McBean, S.; Smail, Nacer F.; Hay, J.; Medical Research Scotland; The Carnegie Trust
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    Post-prandial effects of a meal rich in long-chain omega-3 fatty acids on indicators of cardiovascular risk
    (2012) McKenzie, Jane; Gow, Iain F.; Findlay, S.; Petit, J.; Goua, M.; Wainwright, C.; Davidson, Isobel
    Introduction Evidence from epidemiological studies indicates that the regular consumption of oily fish may be protective against the risk of cardiovascular disease. The benefits appear to be related to the content of long-chain omega-3 fatty acids (LC n-3 PUFA), specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Current UK dietary guidelines therefore recommend the consumption of two portions of fish per week, one of which should be oily (1), which equates to 0.45g LC n-3 PUFA per day. Although there is limited information about intakes of EPA and DHA in Scotland, recent studies show that they are consistently below recommendations (2). Further review of the dietary intake data indicates that the consumption of oily fish is sporadic and inconsistent (3) despite attempts to promote regular intake. Several of the mechanisms involved in the development of cardiovascular disease (CVD) involve endothelial function. Post-prandial hyperlipidaemia has been linked to an increased risk of CVD (4), which is largely attributed to the transient (2-6 hour) decrease in endothelial function (5). Changes in endothelial function have also been shown to be associated with superoxide production (6), implicating oxidative stress as a possible mechanism for endothelial dysfunction. The long-term effects of LC n-3 PUFA on oxidative stress and inflammation are well established, however little is known about their immediate post-prandial effects. Identifying the possible benefits of consumption of a single meal rich in LC n-3 PUFA may provide a new perspective on which to promote dietary changes. The aim of this pilot project was therefore to identify post-prandial changes in markers of cardiovascular risk, assessed by measurement of arterial compliance, whole blood fatty acid profile, plasma glucose and insulin, markers of endothelial dysfunction, oxidative stress and antioxidant status in response a test meal naturally rich LC n-3 PUFA compared with a control meal.