Use of hamster as a model to study diet-induced atherosclerosis

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

Effect of an isoenergetic traditional Mediterranean diet on apolipoprotein A-I kinetic in men with metabolic syndrome

BACKGROUND: The impact of the Mediterranean diet (MedDiet) on high-density lipoprotein (HDL) kinetics has not been studied to date. The objective of this study was therefore to investigate the effect of the MedDiet in the absence of changes in body weight on apolipoprotein (apo) A-I kinetic in men with metabolic syndrome (MetS). METHODS: Twenty-six men with MetS (NCEP-ATP III) were recruited from the general community. In this fixed sequence study, participants’ diet was first standardized to a control diet reflecting current averages in macronutrient intake in North American men, with all foods and beverages provided under isoenergetic conditions for 5 weeks. Participants were then fed an isoenergetic MedDiet over a subsequent period of 5 weeks to maintain their weight constant. During the last week of each diet, participants received a single bolus dose of [5,5,5-(2)H(3)] (L)-leucine and fasting blood samples were collected at predetermined time points. ApoA-I kinetic was determined by multicompartmental modeling using isotopic enrichment data over time. Data were analyses using MIXED models. RESULTS: The response of HDL-cholesterol (C) to MedDiet was heterogeneous, such that there was no mean change compared with the control diet. Plasma apoA-I concentration (−3.9%) and pool size (−5.3%, both P < 0.05) were significantly lower after MedDiet and apoA-I production rate tended to be reduced (−5.7%, P = 0.07) with no change in apoA-I fractional catabolic rate (FCR, -1.6%, P = 0.64). Participants among whom HDL-C concentrations were increased with MedDiet (responders: mean ∆HDL-C: +9.9 ± 3.2%, N = 11) showed significantly greater reductions in apoA-I FCR and in apoB and very-low-density lipoprotein-triglycerides (VLDL-TG) concentrations (all P < 0.04) than those among whom HDL-C levels were reduced after the MedDiet (non-responders: mean ∆HDL-C: -12.0 ± 3.9%, N = 8). Correlation analysis revealed that only variations in apoA-I FCR (r = -0.48, P = 0.01) and in plasma VLDL-TG (r = −0.45, P = 0.03) concentrations were correlated with the individual HDL-C response to the MedDiet. CONCLUSIONS: Data from this controlled feeding study suggest that the heterogeneous response of HDL-C to MedDiet, in the absence of important weight loss, is primarily related to individual variations in apoA-I FCR and in plasma VLDL-TG concentrations. TRIAL REGISTRATION: ClinicalTrial.gov registration number: NCT0098865

Changes in cholesterol homeostasis modify the response of F1B hamsters to dietary very long chain n-3 and n-6 polyunsaturated fatty acids

<p>Abstract</p> <p>Background</p> <p>The plasma lipoprotein response of F1B Golden-Syrian hamsters fed diets high in very long chain (VLC) n-3 polyunsaturated fatty acids (PUFA) is paradoxical to that observed in humans. This anomaly is attributed, in part, to low lipoprotein lipase activity and is dependent on cholesterol status. To further elucidate the mechanism(s) for these responses, hamsters were fed diets containing supplemental fish oil (VLC n-3 PUFA) or safflower oil (n-6 PUFA) (both 10% [w/w]) and either cholesterol-supplemented (0.1% cholesterol [w/w]) or cholesterol-depleted (0.01% cholesterol [w/w] and 10 days prior to killing fed 0.15% lovastatin+2% cholestyramine [w/w]).</p> <p>Results</p> <p>Cholesterol-supplemented hamsters fed fish oil, relative to safflower oil, had higher non-high density lipoprotein (HDL) cholesterol and triglyceride concentrations (P < 0.001) which were associated with lower hepatic low density lipoprotein (LDL) receptor, sterol regulatory element binding protein (SREBP)-1c and acyl-CoA: cholesterol acyl transferase-2 (ACAT) mRNA and protein (p < 0.05), and higher hepatic apolipoprotein (apo) B-100 and apo E protein levels. In contrast, cholesterol-depleted hamsters fed fish oil, relative to safflower oil, had lower non-HDL cholesterol and triglyceride concentrations (P < 0.001) which were associated with lower hepatic SREBP-1c (p < 0.05) but not apo B-100, apo E or ACAT-2 mRNA or protein levels. Independent of cholesterol status, fish oil fed hamsters had lower HDL cholesterol concentrations (p < 0.001), which were associated with lower hepatic apoA-I protein levels (p < 0.05).</p> <p>Conclusion</p> <p>These data suggest disturbing cholesterol homeostasis in F1B hamsters alters their response to dietary fatty acids, which is reflected in altered plasma lipoprotein patterns and regulation of genes associated with their metabolism.</p

Genetic and environmental influences on eating behavior - a study of twin pairs reared apart or reared together

This study examined the relative influence of genetic versus environmental factors on specific aspects of eating behavior. Adult monozygotic twins (22 pairs and 3 singleton reared apart, 38 pairs and 9 singleton reared together, age 18-76 years, BMI 17-43 kg/m2) completed the Three Factor Eating Questionnaire. Genetic and environmental variance components were determined for the three eating behavior constructs and their subscales using model-fitting univariate and multivariate analyses. Unique environmental factors had a substantial influence on all eating behavior variables (explaining 45-71% of variance), and most strongly influenced external locus for hunger and strategic dieting behavior of restraint (explaining 71% and 69% of variance, respectively). Genetic factors had a statistically significant influence on only 4 variables: restraint, emotional susceptibility to disinhibition, situational susceptibility to disinhibition, and internal locus for hunger (heritabilities were 52%, 55%, 38% and 50%, respectively). Common environmental factors did not statistically significantly influence any variable assessed in this study. In addition, multivariate analyses showed that disinhibition and hunger share a common influence, while restraint appears to be a distinct construct. These findings suggest that the majority of variation in eating behavior variables is associated with unique environmental factors, and highlights the importance of the environment in facilitating specific eating behaviors that may promote excess weight gain.R01 AR046124 - NIAMS NIH HHS; R01 MH065322 - NIMH NIH HHS; T32 HL069772 - NHLBI NIH HHS; R37 DA018673 - NIDA NIH HHS; R01 DK073321 - NIDDK NIH HHS; R01 DA018673 - NIDA NIH HH

Food based dietary patterns and chronic disease prevention.

Matthias B Schulze and colleagues discuss current knowledge on the associations between dietary patterns and cancer, coronary heart disease, stroke, and type 2 diabetes, focusing on areas of uncertainty and future research direction

Feasibility, Safety and Acceptability of Soy-Based Diet for Pregnant Women: Preliminary Results from a Pilot Randomized Controlled Trial

Background: Previous evidence suggests that soy containing foods may have beneficial effects on lipid and glycemic metabolism. Pregnancy is associated with a progressive deterioration in glucose and lipid metabolism, partially attributable to elevated estrogen concentrations. Little is known about the effects of soy intake on cardiometabolic risk factors in pregnant women. Methods: A pilot RCT was conducted in 30 pregnant women who were randomized to receive counseling to consume a high-soy or low-soy foods containing diet. Assessments (physical measurements, food frequency questionnaires, fasting blood samples) were conducted at 14 and 28 weeks of pregnancy, and 6 weeks’ postpartum. Monthly follow-up calls were conducted to assess safety and encourage adherence. Results: Both the high-soy and low-soy groups demonstrated high adherence (80-90%), defined as consuming soy foods ≥ 15 days in the past four weeks for high-soy group and ≤ 5 days for low-soy group. Five adverse events possibly associated with soy intake were reported (nausea, vomiting, diarrhea, itchy mouth); all were transient and resolved without sequelae. The high-soy group lost body fat between baseline and postpartum while the low-soy group gained body fat, as reflected by change in triceps skinfold thickness (-4.8 mm vs +3.6 mm, p=0.04). There was a trend towards an improvement in BMI in the high-soy group, both at 28 weeks (+1.4 vs. +3.6 kg/m2, p=0.15) and postpartum (-1.2 vs. +0.6 kg/m2, p=0.14). There were no differences between groups in fasting glucose, HDL-C, LDL-C, TG, or VLDL levels. Conclusion: Initial results from this pilot RCT support the acceptability and safety of consuming soy-based whole foods during pregnancy. A larger-scale RCT is needed to further elucidate the effects of soy diet on cardiometabolic risk among pregnant women

Associations of Bone Mineral Density with Lean Mass, Fat Mass, and Physical Activity in Young Overweight and Obese Women - A Feasibility Study

International Journal of Exercise Science 15(7): 585-598, 2022. To examine the associations between bone mineral density (BMD), body composition and habitual physical activity in women who are overweight/obese. We measured whole-body bone, and body composition (lean mass, fat mass, and total fat percent) via dual-energy x-ray absorptiometry (model General Electric Lunar whole-body scanner) in a diverse group of women (N=48, age 26.6+/-4.7 years, 63% Black) living in an urban setting. The relations between BMD with total fat percent [%]), lean mass (kg), fat mass (kg), and physical activity were examined using Pearson correlations and multiple linear regression models, adjusted for race, age, and dietary calcium. BMD was positively correlated with lean mass (r=0.43, p=0.002) and negatively correlated with total fat percentage (r=-0.31, p=0.03). Multiple linear regression models indicated BMD was positively associated with lean mass (β: 0.007, p\u3c0.001), and negatively associated with fat mass (kg) and total fat percentage (β: -0.003, p=0.03; β: -0.004, p=0.03, respectively). When stratified by race, these relations were maintained in white women but only lean mass in Black women. When stratified by age, the positive correlation between BMD and lean mass was significant in younger women (\u3c30y) only. There were no significant relationships between BMD and any physical activity measures. Our results indicate that in young women who are overweight/obese BMD is significantly associated with body composition, both lean mass and total fat percentage, but not habitual physical activity. An emphasis on lean mass accrual may be valuable for young women, particularly Black women, to improve bone health