Cholesterol transfer to high-density lipoprotein in obesity and the effects of weight loss after bariatric surgery.

Obesity increases serum triglycerides and decreases high-density lipoprotein cholesterol (HDL-C). The objective is to explore some functions of HDL, cholesterol transfers and antioxidant, in subjects with grade I (G1-OB) and III (G3-OB) obesity and effects of bariatric surgery on G3-OB. Fifteen G3-OB patients (43 ± 6 years, BMI 49 ± 3 kg/m2) were studied before and 1 year after bariatric surgery; 15 G1-OB (32 ± 2 years, 32 ± 2 kg/m2) and 15 normal weight (NW) (38 ± 6 years, 22 ± 1 kg/m2) were also studied. HDL diameter, cholesterol transfer to HDL and antioxidant capacity of HDL were determined. G3-OB had higher triglycerides and lower HDL-C; G1-OB had higher triglycerides than NW but HDL-C was equal. Compared to NW, HDL size was smaller in G3-OB but equal in G1-OB. One year after bariatric surgery, BMI and triglycerides of G3-OB decreased (p < .0001 and p = .0012, respectively) and HDL-C increased (p < .0001), equalling of NW group. Antioxidant capacity and cholesterol transfers were not different in groups and were unchanged 1 year after bariatric surgery in G3-OB. HDL antioxidant capacity and transfer of cholesterol to HDL were not defective in obesity despite HDL-C reduction and smaller HDL size. In addition, pronounced weight loss by bariatric surgery did not change those protective functions.

The Interplay of Sirtuin-1, LDL-Cholesterol, and HDL Function: A Randomized Controlled Trial Comparing the Effects of Energy Restriction and Atorvastatin on Women with Premature Coronary Artery Disease.

INTRODUCTION: HDL function has gained prominence in the literature as there is a greater predictive capacity for risk in early coronary artery disease when compared to the traditional parameters. However, it is unclear how dietary energy restriction and atorvastatin influence HDL function. METHODS: A randomized controlled trial with 39 women with early CAD divided into three groups (n = 13): energy restriction (30% of VET), atorvastatin (80 mg), and control. Analyses of traditional biochemical markers (lipid and glucose profile), circulating Sirt-1, and HDL function (lipid composition, lipid transfer, and antioxidant capacity). RESULTS: Participants' mean age was 50.5 ± 3.8 years. Energy restriction increased Sirt-1 by 63.6 pg/mL (95%CI: 1.5-125.7; p = 0.045) and reduced BMI by 0.8 kg/m2 (95%CI: -1.349--0.273; p = 0.004) in a manner independent of other cardiometabolic factors. Atorvastatin reduced LDL-c by 40.0 mg/dL (95%CI: -69.910--10.1; p = 0.010). Increased Sirt-1 and reduced BMI were independently associated with reduced phospholipid composition of HDL (respectively, ß = -0.071; CI95%:-0.136--0.006; p = 0.033; ß = 7.486; CI95%:0.350-14.622; p = 0.040). Reduction in BMI was associated with lower HDL-free cholesterol (ß = 0.818; CI95%:0.044-1.593; p = 0.039). LDL-c reduction by statins was associated with reduced maximal lipid peroxide production rate of HDL (ß = 0.002; CI95%:0.000-0.003; p = 0.022) and total conjugated diene generation (ß = 0.001; CI95%:0.000-0.001; p = 0.029). CONCLUSION: This study showed that energy restriction and atorvastatin administration were associated with changes in lipid profile, serum Sirt-1 concentrations, and HDL function.

Disturbances of the transfer of cholesterol to high-density lipoprotein (HDL) in patients with peripheral artery disease with or without type 2 diabetes mellitus.

INTRODUCTION: Low high-density lipoprotein (HDL)-cholesterol is frequent in patients with peripheral artery disease (PAD) and also in type 2 diabetes mellitus (T2DM), the major risk factor for PAD. The transfer of cholesterol from the other lipoproteins to HDL is an important aspect of HDL metabolism and function, and may contribute to atherogenic mechanisms that lead to PAD development. OBJECTIVE: The aim of this study was to investigate the status of cholesterol transfers in patients with PAD without or with T2DM. METHODS: Patients with PAD (n = 19), with PAD and T2DM (PAD + DM, n = 19), and healthy controls (n = 20), all paired for age, sex, and BMI were studied. Transfer of both forms of cholesterol, unesterified (UC) and esterified (EC), was performed by incubating plasma with a donor nanoemulsion containing radioactive UC and EC, followed by chemical precipitation and HDL radioactive counting. RESULTS: Low-density lipoprotein (LDL)-cholesterol and triglycerides were similar in the three groups. Compared to controls, HDL-C was lower in PAD + DM (p < 0.05), but not in PAD. Transfer of UC was lower in PAD + DM than in PAD and controls (4.18 ± 1.17%, 5.13 ± 1.44%, 6.59 ± 1.25%, respectively, p < 0.001). EC transfer tended to be lower in PAD + DM than in controls (2.96 ± 0.60 vs 4.12 ± 0.89%, p = 0.05). Concentrations of cholesteryl ester transfer protein (CETP) and lecithin-cholesterol acyltransferase (LCAT), both involved in HDL metabolism, were not different among the three groups. CONCLUSION: Deficient cholesterol transfer to HDL may play a role in PAD pathogenesis. Since UC transfer to HDL was lower in PAD + DM compared to PAD alone, it is possible that defective HDL metabolism may contribute to the higher PAD incidence in patients with T2DM.Keywords.

Açai (Euterpe oleracea Mart.) dietary intake affects plasma lipids, apolipoproteins, cholesteryl ester transfer to high-density lipoprotein and redox metabolism: A prospective study in women.

The açai fruit (Euterpe oleracea Martius), which is native to the Brazilian Amazon region, was shown to have high polyphenols and MUFA contents. In this study, we aimed to assess the effects of açai consumption on plasma lipids, apolipoproteins, the transfer of lipids to HDL (which is a relevant HDL function), and some biomarkers of redox metabolism. Forty healthy volunteer women aged 24 ± 3 years consumed 200 g of açai pulp/day for 4 weeks; their clinical variables and blood sample were obtained before and after this period. Açai pulp consumption did not alter anthropometric parameters, systemic arterial pressure, glucose, insulin and total, LDL and HDL cholesterol, triglycerides and apolipoprotein (apo) B, but it did increase the concentration of apo A-I. Açai consumption decreased the ROS, ox-LDL and malondialdehyde while increasing the activity of antioxidative paraoxonase 1. Overall, the total antioxidant capacity (TAC) was increased. Regarding the transfer of plasma lipids to HDL, açai consumption increased the transfer of cholesteryl esters (p = 0.0043) to HDL. Unesterified cholesterol, phospholipids and triglyceride transfers were unaffected. The increase in apo A-I and the cholesteryl ester transfer to HDL after the açai intake period suggests that an improvement in the metabolism of this lipoprotein occurred, and it is well known that HDL is protective against atherosclerosis. Another important finding was the general improvement of the anti-oxidant defences elicited by açai consumption. Our data indicate that açai has favourable actions on plasma HDL metabolism and anti-oxidant defence; therefore açai could have a beneficial overall role against atherosclerosis, and it is a consistently good candidate to consider as a functional food.

Lipid transfers to HDL are diminished in long-term bedridden patients: association with low HDL-cholesterol and increased inflammatory markers.

Plasma lipids have been extensively studied in sedentary and in subjects practicing exercise training, but not in extreme inactivity as occurs in bedridden patients. This is important for the care of bedridden patients and understanding the overall plasma lipid regulation. Here, we investigated plasma lipids, lipid transfers to HDL and inflammatory markers in bedridden patients. Fasting blood samples were collected from 23 clinically stable bedridden patients under long-term care (>90 days) and 26 normolipidemic sedentary subjects, paired for age and gender. In vitro transfer of four lipids to HDL was performed by incubating plasma with donor nanoparticles containing radioactive lipids. Total (193 ± 36 vs 160 ± 43, p = 0.005), LDL (124 ± 3 vs 96 ± 33 p = 0.003) and HDL-cholesterol (45 ± 10 vs 36 ± 13, p = 0.008), apolipoprotein A-I (134 ± 20 vs 111 ± 24, p = 0.001) and oxidized LDL (53 ± 13 vs 43 ± 12, p = 0.011) were lower in bedridden patients, whereas triglycerides, apolipoprotein B, CETP and LCAT were equal in both groups. Transfers of all lipids, namely unesterified cholesterol, cholesterol esters, triglycerides and phospholipids, to HDL were lower in bedridden patients, probably due to their lower HDL-cholesterol levels. Concentrations of IL-1ß, IL-6, IL-8, HGF and NGF were higher in bedridden patients compared to sedentary subjects. In conclusion, inactivity had great impact on HDL, by lowering HDL-cholesterol, apolipoprotein A-I and thereby cholesterol transfers to the lipoprotein, which suggests that inactivity may deteriorate HDL protection beyond the ordinary sedentary condition.

Alveolar osseous defect in rat for cell therapy: preliminary report.

PURPOSE: To study were to reproduce an alveolar bone defect model in Wistar rats to be used for testing the efficacy of stem cell therapies. Additionally, we also aimed to determine the osteogenesis process of this osseous defect in the 1 month period post-surgery. METHODS: The animals were randomly divided into two groups of 7 animals each. A gingivobuccal incision was made, and a bone defect of 28 mm(2) of area was performed in the alveolar region. Animals were killed at 2 weeks after surgery (n=7) and 4 weeks after surgery (n=7). RESULTS: The average area of the alveolar defect at time point of 2 weeks was 22.27 +/- 1.31 mm(2) and the average area of alveolar defect at time point of 4 weeks was 9.03 +/- 1.17 mm(2). The average amount of bone formation at time point of 2 weeks was 5.73 +/- 1.31 mm(2) and the average amount of bone formation at time point of 4 weeks was 19 +/- 1.17 mm(2). Statistically significant differences between the amount of bone formation at 2 weeks and 4 weeks after surgery were seen (p=0.003). CONCLUSION: The highest rate of ossification occurred mostly from 2 to 4 weeks after surgery. This observation suggests that 4 weeks after the bone defect creation should be a satisfactory timing to assess the potential of bone inductive stem cells to accelerate bone regeneration in Wistar rats.

Alveolar osseous defect in rat for cell therapy: preliminary report / Defeito ósseo alveolar em ratos para terapia celular: estudo preliminar

PURPOSE: To study were to reproduce an alveolar bone defect model in Wistar rats to be used for testing the efficacy of stem cell therapies. Additionally, we also aimed to determine the osteogenesis process of this osseous defect in the 1 month period post-surgery. METHODS: The animals were randomly divided into two groups of 7 animals each. A gingivobuccal incision was made, and a bone defect of 28 mm² of area was performed in the alveolar region. Animals were killed at 2 weeks after surgery (n=7) and 4 weeks after surgery (n=7). RESULTS: The average area of the alveolar defect at time point of 2 weeks was 22.27 ± 1.31 mm² and the average area of alveolar defect at time point of 4 weeks was 9.03 ± 1.17 mm². The average amount of bone formation at time point of 2 weeks was 5.73 ± 1.31 mm² and the average amount of bone formation at time point of 4 weeks was 19 ± 1.17 mm². Statistically significant differences between the amount of bone formation at 2 weeks and 4 weeks after surgery were seen (p=0.003). CONCLUSION: The highest rate of ossification occurred mostly from 2 to 4 weeks after surgery. This observation suggests that 4 weeks after the bone defect creation should be a satisfactory timing to assess the potential of bone inductive stem cells to accelerate bone regeneration in Wistar rats.

OBJETIVO: Reproduzir um novo modelo de defeito ósseo alveolar em ratos Wistar que será utilizado para terapia genética e estudos com células tronco. Adicionalmente, outro objetivo do presente estudo foi determinar o pico de regeneração óssea do defeito criado na região alveolar do modelo experimental. MÉTODOS: Os animais foram aleatoriamente divididos em dois grupos de sete animais. Através de uma incisão gengivobucal foi criado um defeito ósseo medindo 28 mm² de área na região alveolar dos ratos. Os ratos foram sacrificados após duas semanas (n=7) e quatro semanas (n=7) da cirurgia. RESULTADOS: A área média do defeito alveolar após duas semanas de cirurgia foi de 22.27 ± 1.31 mm² e a área média do defeito alveolar após quatro semanas de cirurgia foi de 9.03 ± 1.17 mm². A taxa de formação óssea foi de 5.73 ± 1.31 mm² após duas semanas de cirurgia e de 19 ± 1.17 mm² após quatro semanas de cirurgia. Foi observada diferença estatisticamente significante na taxa de formação óssea entre o grupo dos animais sacrificados com duas e quatro semanas (p=0.003). CONCLUSÃO: Este estudo demonstrou que a maior taxa de regeneração óssea ocorreu no período entre duas e quatro semanas após a cirurgia de criação do defeito ósseo alveolar, portanto esta observação sugere que o período de tempo de quatro semanas será suficiente para avaliar a capacidade de células tronco em regenerar osso em ratos Wistar com defeito ósseo alveolar.