Alice Dillard

Tufts University, Boston, GA, United States

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Publications (6)20.13 Total impact

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    ABSTRACT: Dietary modification alters plasma lipoprotein profiles and atherosclerotic lesion progression in humans and some animal models. Variability in response to diet induced atherosclerosis has been reported in hamsters. Assessed was the interaction between background diet composition and dietary fat type on aortic cholesterol accumulation, lipoprotein profiles, hepatic lipids and selected genes. F1B Golden Syrian hamsters (20/group) were fed (12 weeks) semi-purified or non-purified diets containing either 10 % (w/w) coconut oil or safflower oil and 0.15 % (w/w) cholesterol. The non-purified diets relative to semi-purified diets resulted in significantly higher TC (72 % [percent difference] and 38 %, coconut oil and safflower oil, respectively) and nHDL-C (84 and 61 %, coconut oil and safflower oil, respectively), and lower HDL-C (-47 and -45 %, coconut oil and safflower oil, respectively) concentrations. Plasma triacylglycerol concentrations in the hamsters fed the non-purified coconut oil-supplemented diets were three- to fourfold higher than non-purified safflower oil-supplemented, and both semi-purified diets. With the exception of HDL-C, a significant effect of fat type was observed in TC, nHDL-C and triacylglycerol (all P < 0.05) concentrations. Regardless of diet induced differences in lipoprotein profiles, there was no significant effect on aortic cholesterol accumulation. There was an inverse relationship between plasma nHDL-C and triacylglycerol, and hepatic cholesteryl ester content (P < 0.001). Diet induced differences in hepatic gene transcription (LDL receptor, apoB-100, microsomal transfer protein) were not reflected in protein concentrations. Although hamsters fed non-purified and/or saturated fatty acid-supplemented diets had more atherogenic lipoprotein profiles compared to hamsters fed semi-purified and/or polyunsaturated fatty acid-supplemented diets these differences were not reflected in aortic cholesterol accumulation.
    Lipids 10/2013; · 2.56 Impact Factor
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    ABSTRACT: Dietary fatty acid type alters atherosclerotic lesion progression and macrophage lipid accumulation. Incompletely elucidated are the mechanisms by which fatty acids differing in double-bond geometric or positional configuration alter arterial lipid accumulation. The objective of this study was to evaluate the suitability of using Tamm-Horsfall protein 1 (THP-1) macrophages as a model for human monocytes/macrophages to address this issue. Our hypothesis was that THP-1 macrophages pretreated with ω-3 polyunsaturated fatty acids (PUFA) or fatty acid containing a cis double bond would accumulate less lipid, particularly cholesteryl ester, compared with ω-6 polyunsaturated fatty acids or a fatty acid containing a trans double bond, respectively. THP-1 monocytes were differentiated into macrophages and then incubated with fatty acids for 48 hours. There was an increase in intracellular lipid in response to all the fatty acids assessed, and by response was similar among the fatty acids. The increase in lipid accumulation was contributed to triglyceride and to a lesser extent cholesterol, primarily free cholesterol. These data suggest that free fatty acids bound to bovine serum albumin, regardless of double-bond geometric or positional configuration, induce triglyceride accumulation but had only a modest effect on cholesterol accumulation in THP-1 macrophages. The cells appeared to respond similarly to the assessed fatty acids in terms of amount and type of lipid accumulated. Hence, the THP-1 cell line was not appropriate to test the hypotheses of interest.
    Nutrition research 08/2011; 31(8):625-30. · 2.59 Impact Factor
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    ABSTRACT: Estrogen and testosterone are thought to modulate coronary heart disease (CHD) risk. To examine how these hormones affect human macrophage cholesterol transport, a key factor in atherogenesis, we obtained monocytes from healthy male and postmenopausal female donors (age 50–70 years). Cells were allowed to differentiate in autologous serum. Human monocyte-derived macrophages (HMDMs) were exposed to estrogen, testosterone, or vehicle, during differentiation.Cells were cholesterol enriched with oxidized low-density lipoprotein (oxLDL) in the presence of treatment. Cell cholesterol mass, efflux, and the expression of proteins involved in HMDM cholesterol transport were examined.Estrogen significantly reduced cholesteryl ester (CE) content in both female and male HMDMs while having no measurable effect on cholesterol efflux. Testosterone did not affect cholesterol content or efflux. Both hormones significantly but modestly affected the gene expression of several proteins involved in HMDM transport, yet these effects did not translate into significant changes in protein expression. In THP-1 macrophages, the effect of estrogen on CE content was more potent in unloaded macrophages and was estrogen receptor dependent. A trend for a reduction in nonoxLDL uptake by estrogen was observed and was also found to be dependent upon estrogen receptor activation. Our data indicate that estrogen, but not testosterone, reduces CE accumulation in HMDMs obtained from a CHD age relevant population, independent of changes in the expression of proteins important to macrophage cholesterol transport. In THP-1 cells, this effect is reduced in the presence of oxLDL, indicating that a pro-atherogenic lipoprotein milieu is an important variable in sex hormone modulation of CHD.
    Journal of Molecular Endocrinology 01/2011; 47(1):109-117. · 3.58 Impact Factor
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    ABSTRACT: Inflammation plays a central role in the development and progression of coronary heart disease (CHD). The sex hormones estrogen and testosterone have been shown to modify the inflammatory response by influencing cytokine expression in human macrophages obtained from younger individuals. The effect of these hormones on the expression of proinflammatory markers in macrophages obtained from a CHD age-relevant population has not been studied. Human monocyte-derived macrophages (HMDMs) were obtained from healthy normolipidemic men and postmenopausal women (age 50-70 years), and cultured in autologous serum along with both physiological and supraphysiological concentrations of estrogen or testosterone. HMDMs were stimulated with oxidized low-density lipoproteins, and the expression of the cytokines tumor necrosis factor alpha (TNF-alpha or TNF), interleukin (IL)6, and IL-1 beta (IL1B) and of the acute-phase protein C-reactive protein (CRP) was measured. Both physiological and supraphysiological concentrations of testosterone reduced the expression and secretion of TNF-alpha and reduced the expression of IL-1 beta, but did not affect the expression of IL6 or CRP. Estrogen did not modify the expression of TNF-alpha, IL6, and IL-1 beta. Estrogen caused a variable response in CRP expression that was positively associated with the plasma small dense LDL-cholesterol concentration of the donors. There were no gender differences in any of the observed effects. Our results indicate that testosterone may exert anti-inflammatory effects by reducing macrophage TNF-alpha expression, while the effects of estrogen on macrophage CRP expression may depend upon the extracellular lipid environment.
    Journal of Endocrinology 08/2010; 206(2):217-24. · 4.06 Impact Factor
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    ABSTRACT: Golden-Syrian hamsters have been used as an animal model to assess diet-induced atherosclerosis since the early 1980s. Advantages appeared to include a low rate of endogenous cholesterol synthesis, receptor-mediated uptake of LDL cholesterol, cholesteryl ester transfer protein activity, hepatic apoB-100 and intestinal apoB-48 secretion, and uptake of the majority of LDL cholesterol via the LDL receptor pathway. Early work suggested hamsters fed high cholesterol and saturated fat diets responded similarly to humans in terms of lipoprotein metabolism and aortic lesion morphology. Recent work has not consistently replicated these findings. Reviewed was the literature related to controlled hamster feeding studies that assessed the effect of strain, background diet (non-purified, semi-purified) and dietary perturbation (cholesterol and/or fat) on plasma lipoprotein profiles and atherosclerotic lesion formation. F1B hamsters fed a non-purified cholesterol/fat-supplemented diet had more atherogenic lipoprotein profiles (nHDL-C > HDL-C) than other hamster strains or hamsters fed cholesterol/fat-supplemented semi-purified diets. However, fat type; saturated (SFA), monounsaturated or n-6 polyunsaturated (PUFA) had less of an effect on plasma lipoprotein concentrations. Cholesterol- and fish oil-supplemented semi-purified diets yielded highly variable results when compared to SFA or n-6 PUFA, which were antithetical to responses observed in humans. Dietary cholesterol and fat resulted in inconsistent effects on aortic lipid accumulation. No hamster strain was reported to consistently develop lesions regardless of background diet, dietary cholesterol or dietary fat type amount. In conclusion, at this time the Golden-Syrian hamster does not appear to be a useful model to determine the mechanism(s) of diet-induced development of atherosclerotic lesions.
    Nutrition & Metabolism 01/2010; 7:89. · 3.16 Impact Factor
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    ABSTRACT: The lower susceptibility of palmitoleic acid (16:1) to oxidation compared to PUFA may confer functional advantages with respect to finding acceptable alternatives to partially hydrogenated fats, but limited data are available on its effect on cardiovascular risk factors. This study investigated the effect of diets (10% fat, 0.1% cholesterol, wt:wt) enriched with macadamia [monounsaturated fatty acid (MUFA)16:1], palm (SFA,16:0), canola (MUFA,18:1), or safflower (PUFA,18:2) oils on lipoprotein profiles and aortic cholesterol accumulation in F1B Golden Syrian hamsters (n = 16/group). After 12 wk, 8 hamsters in each group were killed (phase 1). The remaining hamsters fed palm oil were changed to a diet containing coconut oil, while hamsters in the other diet groups continued on their original diets for an additional 6 wk (phase 2). With minor exceptions, the time course and dietary SFA source did not alter the study outcomes. Macadamia oil-fed hamsters had lower non-HDL cholesterol and triglyceride concentrations compared with the palm and coconut oil-fed hamsters and higher HDL-cholesterol compared with the coconut, canola, and safflower oil-fed hamsters. The aortic cholesterol concentration was not affected by dietary fat type. The hepatic cholesterol concentration was higher in the unsaturated compared with the saturated oil-fed hamsters. RBC membrane and aortic cholesteryl ester, triglyceride, and phospholipid fatty acid profiles reflected that of the dietary oil. These data suggest that an oil relatively high in palmitoleic acid does not adversely affect plasma lipoprotein profiles or aortic cholesterol accumulation and was similar to other unsaturated fatty acid-rich oils.
    Journal of Nutrition 01/2009; 139(2):215-21. · 4.20 Impact Factor