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HDL-apoA-I kinetics in response to 16 wk of exercise training in men with nonalcoholic fatty liver disease.
Whyte, MB, Shojaee-Moradie, F, Sharaf, SE, Cuthbertson, DJ, Kemp, GJ, Barrett, M, Jackson, NC, Herring, RA, Wright, J, Thomas, EL, et al
American journal of physiology. Endocrinology and metabolism. 2020;(6):E839-E847
Abstract
Nonalcoholic fatty liver disease (NAFLD) is characterized by low-circulating concentration of high-density lipoprotein cholesterol (HDL-C) and raised triacylglycerol (TAG). Exercise reduces hepatic fat content, improves insulin resistance and increases clearance of very-low-density lipoprotein-1 (VLDL1). However, the effect of exercise on TAG and HDL-C metabolism is unknown. We randomized male participants to 16 wk of supervised, moderate-intensity aerobic exercise (n = 15), or conventional lifestyle advice (n = 12). Apolipoprotein A-I (apoA-I) and VLDL-TAG and apolipoprotein B (apoB) kinetics were investigated using stable isotopes (1-[13C]-leucine and 1,1,2,3,3-2H5 glycerol) pre- and postintervention. Participants underwent MRI/spectroscopy to assess changes in visceral fat. Results are means ± SD. At baseline, there were no differences between exercise and control groups for age (52.4 ± 7.5 vs. 52.8 ± 10.3 yr), body mass index (BMI: 31.6 ± 3.2 vs. 31.7 ± 3.6 kg/m2), and waist circumference (109.3 ± 7.5 vs. 110.0 ± 13.6 cm). Percentage of liver fat was 23.8 (interquartile range 9.8-32.5%). Exercise reduced body weight (101.3 ± 10.2 to 97.9 ± 12.2 kg; P < 0.001) and hepatic fat content [from 19.6%, interquartile range (IQR) 14.6-36.1% to 8.9% (4.4-17.8%); P = 0.001] and increased the fraction HDL-C concentration (measured following ultracentrifugation) and apoA-I pool size with no change in the control group. However, plasma and VLDL1-TAG concentrations and HDL-apoA-I fractional catabolic rate (FCR) and production rate (PR) did not change significantly with exercise. Both at baseline (all participants) and after exercise there was an inverse correlation between apoA-I pool size and VLDL-TAG and -apoB pool size. The modest effect of exercise on HDL metabolism may be explained by the lack of effect on plasma and VLDL1-TAG.
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Bariatric Surgery Improves HDL Function Examined by ApoA1 Exchange Rate and Cholesterol Efflux Capacity in Patients with Obesity and Type 2 Diabetes.
Lorkowski, SW, Brubaker, G, Rotroff, DM, Kashyap, SR, Bhatt, DL, Nissen, SE, Schauer, PR, Aminian, A, Smith, JD
Biomolecules. 2020;(4)
Abstract
Bariatric surgery improves glycemic control better than medical therapy; however, the effect of bariatric surgery on HDL function is not well characterized. Serum samples were available at baseline, 1-, and 5-years post procedures, for 90 patients with obesity and type 2 diabetes who were randomized to intensive medical therapy (n = 20), Roux-en-Y gastric bypass (RYGB, n = 37), or sleeve gastrectomy (SG, n = 33) as part of the STAMPEDE clinical trial. We examined serum HDL function by two independent assays, apolipoprotein A-1 exchange rate (AER) and cholesterol efflux capacity (CEC). Compared with baseline, AER was significantly higher at 5 years for participants in all treatment groups, but only increased significantly at 1 year in the RYGB and SG groups. CEC was divided into ABCA1-dependent and independent fractions, and the later was correlated with AER. ABCA1-independent CEC increased significantly only at 5 years in both surgical groups, but did not significantly change in the medical therapy group. There was no significant change in ABCA1-dependent CEC in any group. The increase in AER, but not ABCA1-independent CEC, was correlated with the reduction in body mass index and glycated hemoglobin levels among all subjects at 5 years, indicating that AER as a measure of HDL function would be a better reflection of therapy versus CEC.
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Association of rs670 variant of APOA1 gene with lipid profile and insulin resistance after 9 months of a high protein/low carbohydrate vs a standard hypocaloric diet.
Izaola, O, Primo, D, Gomez Hoyos, E, Lopez Gomez, JJ, Ortola, A, de Luis, D
Clinical nutrition (Edinburgh, Scotland). 2020;(4):988-993
Abstract
BACKGROUND & AIMS A common G-to-A transition (rs670) in the APOA1 gene has been related with metabolism. We evaluate the association of this SNP with changes in lipid profile and insulin resistance in response to two diets. METHODS 268 obese patients were randomly allocated to a high protein/low carbohydrate -Diet HP- vs. a standard hypocaloric diet -Diet S- for 9 months. Anthropometric and biochemical status were evaluated at 3 and 9 months. RESULTS 179 subjects (66.8%) had the genotype GG, 79 patients GA (29.4%) and 10 subjects AA (3,8%). With both diets: the decrease of BMI, weight, waist circumference, fat mass was higher in A allele carriers than non-carriers. Also on both diets A allele carriers showed greater improvements in total cholesterol (-19.0 ± 2.5 mg/dl (non-A allele carriers -12.1 ± 2.0 mg/dl:p = 0.02 after Diet HP) and -13.1 ± 2.1 mg/dl (non-A allele carriers -8.9 ± 1.1 mg/dl:p = 0.02 after Diet S)), LDL-cholesterol (-18.0 ± 2.1 mg/dl (non-A allele carriers -8.3 ± 2.2 mg/dl:p = 0.01 after Diet HP) and -12.0 ± 1.5 mg/dl (non-A allele carriers -6.3 ± 2.3 mg/dl:p = 0.01 after Diet S)), insulin (-2.5 ± 0.2 mUI/L (in non A allele -1.8 ± 0.2 mUI/L:p = 0.01 after Diet HP) and -2.1 ± 0.1 mUI/L (non A allele carriers -1.2 ± 0.3 mUI/L:p = 0.01 after Diet S)), HOMA-IR (-1.3 ± 0.3 units (non A allele group -0.8 ± 0.2:p = 0.03 after Diet HP) and -1.1 ± 0.1 units (non A allele carriers -0.3 ± 0.2 mg/dl:p = 0.01 after Diet S)) than non-A allele carriers. CONCLUSIONS A allele carriers of rs670 ApoA1 polymorphism showed a higher decrease of insulin resistance, LDL cholesterol and adiposity induced by two different hypocaloric diet than non A allele carriers.
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Dysfunctional High-Density Lipoproteins Are Associated With a Greater Incidence of Acute Coronary Syndrome in a Population at High Cardiovascular Risk: A Nested Case-Control Study.
Soria-Florido, MT, Castañer, O, Lassale, C, Estruch, R, Salas-Salvadó, J, Martínez-González, MÁ, Corella, D, Ros, E, Arós, F, Elosua, R, et al
Circulation. 2020;(6):444-453
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Abstract
BACKGROUND Studies have failed to establish a clear link between high-density lipoprotein (HDL) cholesterol and cardiovascular disease, leading to the hypothesis that the atheroprotective role of HDL lies in its biological activity rather than in its cholesterol content. However, to date, the association between HDL functional characteristics and acute coronary syndrome has not been investigated comprehensively. METHODS We conducted a case-control study nested within the PREDIMED (Prevención con Dieta Mediterránea) cohort, originally a randomized trial in which participants followed a Mediterranean or low-fat diet. Incident acute coronary syndrome cases (N=167) were individually matched (1:2) to control patients by sex, age, intervention group, body mass index, and follow-up time. We investigated 2 individual manifestations (myocardial infarction, unstable angina) as secondary outcomes. We measured the following functional characteristics: HDL cholesterol concentration (in plasma); cholesterol efflux capacity; antioxidant ability, measured by the HDL oxidative-inflammatory index; phospholipase A2 activity; and sphingosine-1-phosphate, apolipoproteins A-I and A-IV, serum amyloid A, and complement 3 protein (in apolipoprotein B-depleted plasma). We used conditional logistic regression models adjusted for HDL cholesterol levels and cardiovascular risk factors to estimate odds ratios (ORs) between 1-SD increments in HDL functional characteristics and clinical outcomes. RESULTS Low values of cholesterol efflux capacity (OR1SD, 0.58; 95% CI, 0.40-0.83) and low levels of sphingosine-1-phosphate (OR1SD, 0.70; 95% CI, 0.52-0.92) and apolipoprotein A-I (OR1SD, 0.58; 95% CI, 0.42-0.79) were associated with higher odds of acute coronary syndrome. Higher HDL oxidative inflammatory index values were marginally linked to acute coronary syndrome risk (OR1SD, 1.27; 95% CI, 0.99-1.63). Low values of cholesterol efflux capacity (OR1SD, 0.33; 95% CI, 0.18-0.61), sphingosine-1-phosphate (OR1SD: 0.60; 95% CI: 0.40-0.89), and apolipoprotein A-I (OR1SD, 0.59; 95% CI, 0.37-0.93) were particularly linked to myocardial infarction, whereas high HDL oxidative-inflammatory index values (OR1SD, 1.53; 95% CI, 1.01-2.33) and low apolipoprotein A-I levels (OR1SD, 0.52; 95% CI, 0.31-0.88) were associated with unstable angina. CONCLUSIONS Low cholesterol efflux capacity values, pro-oxidant/proinflammatory HDL particles, and low HDL levels of sphingosine-1-phosphate and apolipoprotein A-I were associated with increased odds of acute coronary syndrome and its manifestations in individuals at high cardiovascular risk. CLINICAL TRIAL REGISTRATION URL: https://www.controlled-trials.com/ISRCTN35739639. Unique identifier: ISRCTN35739639.
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The Beneficial Effects of Alpha Lipoic Acid Supplementation on Lp-PLA2 Mass and Its Distribution between HDL and apoB-Containing Lipoproteins in Type 2 Diabetic Patients: A Randomized, Double-Blind, Placebo-Controlled Trial.
Baziar, N, Nasli-Esfahani, E, Djafarian, K, Qorbani, M, Hedayati, M, Mishani, MA, Faghfoori, Z, Ahmaripour, N, Hosseini, S
Oxidative medicine and cellular longevity. 2020;:5850865
Abstract
Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a new specific vascular inflammation biomarker that is carried by the lipoproteins in the blood and plays a prominent role in the pathogenesis of atherosclerosis. Increased Lp-PLA2 levels and impaired Lp-PLA2 distribution across high-density lipoprotein (HDL) and non-HDL lipoproteins have been reported in diabetic patients, which is associated with the increase in cardiovascular disease (CVD) risk. This study is aimed at investigating the effect of alpha lipoic acid (ALA), as an antioxidant with potential cardioprotective properties, on the Lp-PLA2 mass and its distribution in diabetic patients. In a double-blind, randomized, placebo-controlled clinical trial, seventy diabetic patients were randomly allocated to ALA (1200 mg ALA as two 600 mg capsules/day) and placebo (two maltodextrin capsules/day) groups. The serum levels of total Lp-PLA2 mass, HDL-Lp-PLA2, oxidized low-density lipoproteins (ox-LDL), apolipoprotein A1 (apo A1), lipid profiles, fasting blood sugar (FBS), and insulin were measured, and apolipoprotein B- (apoB-) associated Lp-PLA2 and homeostasis model of assessment index (HOMA-IR) were calculated at the baseline and after 8 weeks of intervention. ALA significantly decreased the ox-LDL, total Lp-PLA2 mass, apoB-associated Lp-PLA2, and percent of apoB-associated Lp-PLA2 and triglyceride and increased the percent of HDL-Lp-PLA2 compared with the placebo group but had no significant effect on HDL-Lp-PLA2 mass, apo A1, lipid profiles, and glycemic indices. There was a positive correlation between the reduction in the ox-LDL level and total Lp-PLA2 mass in the ALA group. In conclusion, ALA may decrease the CVD risk by reducing the ox-LDL and Lp-PLA2 mass and improving the Lp-PLA2 distribution among lipoproteins in type 2 diabetic patients.
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Effects of Living High-Training Low and High on Body Composition and Metabolic Risk Markers in Overweight and Obese Females.
Gao, H, Xu, J, Zhang, L, Lu, Y, Gao, B, Feng, L
BioMed research international. 2020;:3279710
Abstract
This study examined the effects of 4 weeks of living high-training low and high (LHTLH) under moderate hypoxia on body weight, body composition, and metabolic risk markers of overweight and obese females. Nineteen healthy overweight or obese females participated in this study. Participants were assigned to the normoxic training group (NG) or the LHTLH group (HG). The NG participants lived and trained at sea level. The HG participants stayed for approximately 10 hours in a simulated 2300 m normobaric state of hypoxia for six days a week and trained for 2 hours 3 times a week under the same simulated hypoxia. The interventions lasted for 4 weeks. All groups underwent dietary restriction based on resting metabolic rate. The heart rate of the participants was monitored every ten minutes during exercise to ensure that the intensity was in the aerobic range. Compared with the preintervention values, body weight decreased significantly in both the NG and the HG (-8.81 ± 2.09% and -9.09 ± 1.15%, respectively). The fat mass of the arm, leg, trunk, and whole body showed significant reductions in both the NG and the HG, but no significant interaction effect was observed. The percentage of lean soft tissue mass loss in the total body weight loss tended to be lower in the HG (27.61% versus 15.94%, P=0.085). Between the NG and the HG, significant interaction effects of serum total cholesterol (-12.66 ± 9.09% versus -0.05 ± 13.36%,) and apolipoprotein A1 (-13.66 ± 3.61% versus -5.32 ± 11.07%, P=0.042) were observed. A slight increase in serum high-density lipoprotein cholesterol (HDL-C) was observed in the HG (1.12 ± 12.34%) but a decrease was observed in the NG (-11.36 ± 18.91%). The interaction effect of HDL-C between NG and HG exhibited a significant trend (P=0.055). No added effects on serum triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), or APO-B were observed after 4 weeks of LHTLH. In conclusion, 4 weeks of LHTLH combined with dietary restriction could effectively reduce the body weight and body fat mass of overweight and obese females. Compared with training and sleeping under normoxia, no additive benefit of LHTLH on the loss of body weight and body fat mass was exhibited. However, LHTLH may help to relieve the loss of lean soft tissue mass and serum HDL-C.
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[Influence of rs670 variant of APOA1 gene on serum HDL response to an enriched-polyunsaturated vs. an enriched-monounsaturated fat hypocaloric diet].
de Luis Román, DA, Izaola Jáuregui, O, Primo, D, Aller, R
Nutricion hospitalaria. 2019;(6):1288-1295
Abstract
Background and objectives: genetic variants of the APOA1 gene have been related to lipid profile in obese subjects. Our aim was to analyze the effects of the rs670 APOA1 gene polymorphism on metabolic changes secondary to an enriched-polyunsaturated fat vs. an enriched-monounsaturated fat hypocaloric diet. Methods: 360 Caucasian obese subjects were randomly allocated to two groups. One group received an enriched-polyunsaturated fat (diet P) and the other an enriched-monounsaturated fat hypocaloric diet (diet M) during 12 weeks. The effects on serum biomarkers related to lipid and carbohydrate metabolism were evaluated before and after the dietary intervention. Results: after both diets, body mass index, weight, fat mass, waist circumference, systolic blood pressure, plasma leptin concentration, and waist circumference decreased in all patients. After 12 weeks of intervention with diet P, plasma insulin levels and HOMA-IR decreased in A-allele carriers: delta: -7.3 ± 2.2 IU/L (p = 0.01), and delta: -2.8 ± 0.5 units (p = 0.02), respectively. The same changes in delta were observed after diet M in A-allele carriers: insulin delta: -5.9 ± 1.2 IU/L (p = 0.01), and HOMA-IR delta: -2.1 ± 0.8 units (p = 0.02). In A-allele carriers, LDL-cholesterol decreased and HDL-cholesterol increased after the dietary intervention with diet P: delta: -12.1 ± 4.3 mg/dL (p = 0.01), and delta: 2.6 ± 0.7 mg/dL (p = 0.01), respectively. No differences in lipid profile were observed after diet M. These improvements were not observed in non-A-allele carriers after both interventions. Conclusions: our study showed the association of the rs670 ApoA1 polymorphism with insulin resistance changes as induced by both diets. An enriched-polyunsaturated fat diet produced an additional improvement of HDL-cholesterol and LDL-cholesterol in A-allele carriers.
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Role of rs670 variant of APOA1 gene on metabolic response after a high fat vs. a low fat hypocaloric diets in obese human subjects.
de Luis, D, Izaola, O, Primo, D, Aller, R
Journal of diabetes and its complications. 2019;(3):249-254
Abstract
BACKGROUND & AIMS A common G-to-A transition located 75 base pairs upstream (rs670) from transcription start site of the APOA1 gene has been related with some metabolic parameters. Our aim was to analyze the effects of rs670 APOA1 gene polymorphism on lipid profile and metabolic changes after two different hypocaloric diets. METHODS 282 obese subjects were randomly allocated during 12 weeks (Diet HF - high fat diet vs. Diet LF - low fat diet). Anthropometric and biochemical status were evaluated. RESULTS Body mass index, weight, fat mass, waist circumference, systolic blood pressure, leptin levels and waist circumference decreased in all patients in average after both diets. In A allele carriers after 12 weeks with both diets, insulin levels (Delta diet HF: -5.3 + 1.2 UI/L; P = 0.02 and Delta diet LF: -5.8 + 1.3 UI/L; P = 0.02) and HOMA-IR (Delta diet HF: -2.9 + 0.8 units; P = 0.01 and Delta diet LF: -2.2 + 0.9 units; P = 0.03) improved in a significant way. With the low fat diet, A allele carriers showed a statistical improvement in HDL-cholesterol levels (Delta: 4 + 1 mg/dl; P = 0.03). CONCLUSIONS Our study showed the association of rs670 ApoA1 polymorphism with a decrease of insulin resistance induced by both diets and provided additional evidence on HDL-cholesterol increase after a LF hypocaloric diet in A allele carriers.
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Inclusion of Almonds in a Cholesterol-Lowering Diet Improves Plasma HDL Subspecies and Cholesterol Efflux to Serum in Normal-Weight Individuals with Elevated LDL Cholesterol.
Berryman, CE, Fleming, JA, Kris-Etherton, PM
The Journal of nutrition. 2017;(8):1517-1523
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Abstract
Background: Almonds may increase circulating HDL cholesterol when substituted for a high-carbohydrate snack in an isocaloric diet, yet little is known about the effects on HDL biology and function.Objective: The objective was to determine whether incorporating 43 g almonds/d in a cholesterol-lowering diet would improve HDL subspecies and function, which were secondary study outcomes.Methods: In a randomized, 2-period, crossover, controlled-feeding study, a diet with 43 g almonds/d (percentage of total energy: 51% carbohydrate, 16% protein, and 32% total and 8% saturated fat) was compared with a similar diet with an isocaloric muffin substitution (58% carbohydrate, 15% protein, and 26% total and 8% saturated fat) in men and women with elevated LDL cholesterol. Plasma HDL subspecies and cholesterol efflux from J774 macrophages to human serum were measured at baseline and after each diet period. Diet effects were examined in all participants (n = 48) and in normal-weight (body mass index: <25; n = 14) and overweight or obese (≥25; n = 34) participants by using linear mixed models.Results: The almond diet, compared with the control diet, increased α-1 HDL [mean ± SEM: 26.7 ± 1.5 compared with 24.3 ± 1.3 mg apolipoprotein A-I (apoA-I)/dL; P = 0.001]. In normal-weight participants, the almond diet, relative to the control diet, increased α-1 HDL (33.7 ± 3.2 compared with 28.4 ± 2.6 mg apoA-I/dL), the α-1 to pre-β-1 ratio [geometric mean (95% CI): 4.3 (3.3, 5.7) compared with 3.1 (2.4, 4.0)], and non-ATP-binding cassette transporter A1 cholesterol efflux (8.3% ± 0.4% compared with 7.8% ± 0.3%) and decreased pre-β-2 (3.8 ± 0.4 compared with 4.6 ± 0.4 mg apoA-I/dL) and α-3 (23.5 ± 0.9 compared with 26.9 ± 1.1 mg apoA-I/dL) HDL (P < 0.05). No diet effects were observed in the overweight or obese group.Conclusions: Substituting almonds for a carbohydrate-rich snack within a lower-saturated-fat diet may be a simple strategy to maintain a favorable circulating HDL subpopulation distribution and improve cholesterol efflux in normal-weight individuals with elevated LDL cholesterol. This trial was registered at clinicaltrials.gov as NCT01101230.
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Association of High-Density Lipoprotein-Cholesterol Versus Apolipoprotein A-I With Risk of Coronary Heart Disease: The European Prospective Investigation Into Cancer-Norfolk Prospective Population Study, the Atherosclerosis Risk in Communities Study, and the Women's Health Study.
van Capelleveen, JC, Bochem, AE, Boekholdt, SM, Mora, S, Hoogeveen, RC, Ballantyne, CM, Ridker, PM, Sun, W, Barter, PJ, Tall, AR, et al
Journal of the American Heart Association. 2017;(8)
Abstract
BACKGROUND The contribution of apolipoprotein A-I (apoA-I) to coronary heart disease (CHD) risk stratification over and above high-density lipoprotein cholesterol (HDL-C) is unclear. We studied the associations between plasma levels of HDL-C and apoA-I, either alone or combined, with risk of CHD events and cardiovascular risk factors among apparently healthy men and women. METHODS AND RESULTS HDL-C and apoA-I levels were measured among 17 661 participants of the EPIC (European Prospective Investigation into Cancer)-Norfolk prospective population study. Hazard ratios for CHD events and distributions of risk factors were calculated by quartiles of HDL-C and apoA-I. Results were validated using data from the ARIC (Atherosclerosis Risk in Communities) and WHS (Women's Health Study) cohorts, comprising 15 494 and 27 552 individuals, respectively. In EPIC-Norfolk, both HDL-C and apoA-I quartiles were strongly and inversely associated with CHD risk. Within HDL-C quartiles, higher apoA-I levels were not associated with lower CHD risk; in fact, CHD risk was higher within some HDL-C quartiles. ApoA-I levels were associated with higher levels of CHD risk factors: higher body mass index, HbA1c, non-HDL-C, triglycerides, apolipoprotein B, systolic blood pressure, and C-reactive protein, within fixed HDL-C quartiles. In contrast, HDL-C levels were consistently inversely associated with overall CHD risk and CHD risk factors within apoA-I quartiles (P<0.001). These findings were validated in the ARIC and WHS cohorts. CONCLUSIONS Our findings demonstrate that apoA-I levels do not offer predictive information over and above HDL-C. In fact, within some HDL-C quartiles, higher apoA-I levels were associated with higher risk of CHD events, possibly because of the unexpected higher prevalence of cardiovascular risk factors in association with higher apoA-I levels. CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrials.gov. Unique identifier: NCT00000479.