Jose O. Leite

Consuming eggs for breakfast influences plasma glucose and ghrelin, while reducing energy intake during the next 24 hours in adult men

We hypothesized that consuming eggs for breakfast would significantly lower postprandial satiety and energy intake throughout the day. Using a crossover design, 21 men, 20 to 70 years old, consumed 2 isoenergetic test breakfasts, in a random order separated by 1 week. The macronutrient composition of the test breakfasts were as follows: (EGG, % CHO/fat/protein = 22:55:23) and (BAGEL, % CHO/fat/protein = 72:12:16). Fasting blood samples were drawn at baseline before the test breakfast and at 30, 60, 120, and 180 minutes after breakfast. After 180 minutes, subjects were given a buffet lunch and asked to eat until satisfied. Subjects filled out Visual Analog Scales (VAS) during each blood draw and recorded food intake the days before and after the test breakfasts. Plasma glucose, insulin, and appetite hormones were analyzed at each time point. Subjects consumed fewer kilocalories after the EGG breakfast compared with the BAGEL breakfast (P< .01). In addition, subjects consumed more kilocalories in the 24-hour period after the BAGEL compared with the EGG breakfast (P < .05). Based on VAS, subjects were hungrier and less satisfied 3 hours after the BAGEL breakfast compared with the EGG breakfast (P < .01). Participants had higher plasma glucose area under the curve (P < .05) as well as an increased ghrelin and insulin area under the curve with BAGEL (P < .05). These findings suggest that consumption of eggs for breakfast results in less variation of plasma glucose and insulin, a suppressed ghrelin response, and reduced energy intake.

A Lutein-Enriched Diet Prevents Cholesterol Accumulation and Decreases Oxidized LDL and Inflammatory Cytokines in the Aorta of Guinea Pigs

Lutein has been shown to be protective against age-related macular degeneration; however, the antiinflammatory and antioxidant effects of this carotenoid in aortas are less known. Guinea pigs were fed a hypercholesterolemic diet (0.25 g cholesterol/100 g) and randomly allocated to a control group (n = 9) or a lutein group (n = 10) (0.01 g/100 g lutein) [corrected] and fed the experimental diets for 12 wk. Plasma LDL cholesterol and TG did not differ between groups; however, the lutein group had lower concentrations of medium size LDL (P < 0.05). As expected, guinea pigs from the lutein group had higher concentrations of plasma and liver lutein than those from the control group (P < 0.0001). Aortic cholesterol and malondialdehyde concentrations were lower in the lutein group (9.6 ± 2.8 mmol/g and 1.69 ± 1.35 nmol/mg protein) compared to the control group (15.5 ± 2.3 mmol/g and 2.98 ± 1.45 nmol/mg protein) (P < 0.05). Hematoxilin and eosin staining indicated that aortas from the control group presented focal intimal thickening, whereas either less thickness or no visible thickness was present in aortas from the lutein group. Oxidized LDL (oxLDL) was lower both in plasma and aorta in the lutein group compared to the control group (P < 0.001). Aortic cytokines were also lower in the lutein group (P < 0.05). Plasma lutein and oxLDL (r = -0.79; P < 0.0001) and plasma lutein and aortic oxLDL (r = -0.64; P < 0.0001) were negatively correlated. These data suggest that lutein exerts potent antioxidant and antiinflammatory effects in aortic tissue that may protect against development of atherosclerosis in guinea pigs.

A-002 (Varespladib), a phospholipase A2 inhibitor, reduces atherosclerosis in guinea pigs

BackgroundThe association of elevated serum levels of secretory phospholipase A2 (sPLA2) in patients with cardiovascular disease and their presence in atherosclerotic lesions suggest the participation of sPLA2 enzymes in this disease. The presence of more advanced atherosclerotic lesions in mice that overexpress sPLA2 enzymes suggest their involvement in the atherosclerotic process. Therefore, the sPLA2 family of enzymes could provide reasonable targets for the prevention and treatment of atherosclerosis. Thus, A-002 (varespladib), an inhibitor of sPLA2enzymes, is proposed to modulate the development of atherosclerosis.MethodsTwenty-four guinea pigs were fed a high saturated fat, high cholesterol diet (0.25%) for twelve weeks. Animals were treated daily with A-002 (n = 12) or vehicle (10% aqueous acacia; n = 12) by oral gavage. After twelve weeks, animals were sacrificed and plasma, heart and aorta were collected. Plasma lipids were measured by enzymatic methods, lipoprotein particles size by nuclear magnetic resonance, aortic cytokines by a colorimetric method, and aortic sinus by histological analyses.ResultsPlasma total cholesterol, HDL cholesterol and triglycerides were not different among groups. However, the levels of inflammatory cytokines interleukin (IL)-10, IL-12 and granulocyte-macrophage colony-stimulating factor (GM-CSF) were significantly reduced in the treatment group. This group also had a significant 27% reduction in cholesterol accumulation in aorta compared with placebo group. Morphological analysis of aortic sinus revealed that the group treated with A-002 reduced atherosclerotic lesions by 24%.ConclusionThe use of A-002 may have a beneficial effect in preventing diet-induced atherosclerosis in guinea pigs.

Low-carbohydrate diets reduce lipid accumulation and arterial inflammation in guinea pigs fed a high-cholesterol diet.

INTRODUCTION Low-carbohydrate diets (LCD) efficiently induce weight loss and favorably affect plasma lipids, however, the effect of LCD on atherosclerosis is still argued. OBJECTIVE To evaluate the effect of LCD on the prevention of atherosclerosis. METHODS Twenty guinea pigs were fed either a LCD or a low-fat diet (LFD) in combination with high-cholesterol (0.25g/100g) for 12 weeks. The percentage energy of macronutrient distribution was 10:65:25 for carbohydrate:fat:protein for the LCD, and 55:20:25 for the LFD. Plasma lipids were measured using colorimetric assays. Plasma and aortic oxidized (oxLDL) were quantified using ELISA methods. Inflammatory cytokines were measured in aortic homogenates using an immunoassay. H&E stained sections of aortic sinus and Schultz stained sections of carotid arteries were examined. RESULTS LDL cholesterol was lower in the LCD compared to the LFD group (71.9+/-34.8 vs. 81.7+/-26.9mg/dL; p=0.039). Aortic cholesterol was also lower in the LCD (4.98+/-1.3mg/g) compared to the LFD group (6.68+/-2.0mg/g); p<0.05. The Schultz staining method confirmed less aortic cholesterol accumulation in the LCD group. Plasma oxLDL did not differ between groups, however, aortic oxLDL was 61% lower in the LCD compared to the LFD group (p=0.045). There was a positive correlation (r=0.63, p=0.03) between oxLDL and cholesterol concentration in the aorta of LFD group, which was not observed in LCD group (r=-0.05, p=0.96). Inflammatory markers were reduced in guinea pigs from the LCD group (p<0.05) and they were correlated with the decreases in oxLDL in aorta. CONCLUSION These results suggest that LCD not only decreases lipid deposition, but also prevents the accumulation of oxLDL and reduces inflammatory cytokines within the arterial wall and may prevent atherosclerosis.

Low HDL cholesterol is associated with increased atherogenic lipoproteins and insulin resistance in women classified with metabolic syndrome

Both metabolic syndrome (MetS) and elevated LDL cholesterol (LDL-C) increase the risk for cardiovascular disease (CVD). We hypothesized that low HDL cholesterol (HDL-C) would further increase CVD risk in women having both conditions. To assess this, we recruited 89 women with MetS (25-72 y) and LDL-C ≥ 2.6 mmol/L. To determine whether plasma HDL-C concentrations were associated with dietary components, circulating atherogenic particles, and other risk factors for CVD, we divided the subjects into two groups: high HDL-C (H-HDL) (≥ 1.3 mmol/L, n = 32) and low HDL-C (L-HDL) (< 1.3 mmol/L, n = 57). Plasma lipids, insulin, adiponectin, apolipoproteins, oxidized LDL, Lipoprotein(a), and lipoprotein size and subfractions were measured, and 3-d dietary records were used to assess macronutrient intake. Women with L-HDL had higher sugar intake and glycemic load (P < 0.05), higher plasma insulin (P < 0.01), lower adiponectin (P < 0.05), and higher numbers of atherogenic lipoproteins such as large VLDL (P < 0.01) and small LDL (P < 0.001) than the H-HDL group. Women with L-HDL also had larger VLDL and both smaller LDL and HDL particle diameters (P < 0.001). HDL-C was positively correlated with LDL size (r = 0.691, P < 0.0001) and HDL size (r = 0.606, P < 0.001), and inversely correlated with VLDL size (r = -0.327, P < 0.01). We concluded that L-HDL could be used as a marker for increased numbers of circulating atherogenic lipoproteins as well as increased insulin resistance in women who are already at risk for CVD.

Low-carbohydrate diet disrupts the association between insulin resistance and weight gain

The cornerstone to treat metabolic syndrome and insulin resistance is dietary intervention. Both low-carbohydrate diet (LCD) and low-fat diet (LFD) have been reported to induce weight loss and improve these conditions. One of the factors associated with a subjects adherence to the diet is satiety. The aim of this study was to evaluate the effects of LCD and LFD on body weight, appetite hormones, and insulin resistance. Twenty guinea pigs were randomly assigned to LCD or LFD (60%:10%:30% or 20%:55%:25% of energy from fat/carbohydrate/protein, respectively) for 12 weeks. Weight and food intake were recorded every week. After this period, animals were killed and plasma was obtained to measure plasma glucose and insulin, appetite hormones, and ketone bodies. Guinea pigs fed LCD gained more weight than those fed LFD. The daily amount of food intake in grams was not different between groups, suggesting that food density and gastric distension played a role in satiety. There was no difference in leptin levels, which excludes the hypothesis of leptin resistance in the LCD group. However, plasma glucagon-like peptide-1 was 47.1% lower in animals fed LCD (P < .05). Plasma glucose, plasma insulin, and insulin sensitivity were not different between groups. However, the heavier animals that were fed LFD had impairment in insulin sensitivity, which was not observed in those fed LCD. These findings suggest that satiety was dependent on the amount of food ingested. The weight gain in animals fed LCD may be related to their greater caloric intake, lower levels of glucagon-like peptide-1, and higher protein consumption. The adoption of LCD promotes a unique metabolic state that prevents insulin resistance, even in guinea pigs that gained more weight. The association between weight gain and insulin resistance seems to be dependent on high carbohydrate intake.

Carbohydrate restriction and dietary cholesterol distinctly affect plasma lipids and lipoprotein subfractions in adult guinea pigs

To evaluate the effects of carbohydrate restriction (CR) and dietary cholesterol on lipoprotein metabolism, adult male guinea pigs (10 guinea pigs/diet) were fed either low (0.04 g/100 g) or high (0.25 g/100 g) amounts of dietary cholesterol, in combination with either low (10% total energy) or high (54.2% total energy) dietary carbohydrate (control groups) for a total of four groups: high carbohydrate-low cholesterol (control-L), high carbohydrate-high cholesterol (control-H), low carbohydrate-low cholesterol (CR-L) and low carbohydrate-high cholesterol (CR-H). Plasma triglyceride concentrations were lower (P<.01%), while high-density lipoprotein cholesterol concentrations were higher (P<.05) in the CR groups compared to the control groups. In contrast, high dietary cholesterol (CR-H and control-H) resulted in higher concentrations of total and low-density lipoprotein (LDL) cholesterol compared to those guinea pigs fed the low-cholesterol diets (P<.01). Dietary cholesterol significantly increased the total number of LDL particles (P<.001) and the number of small LDL (P<.001), as determined by nuclear magnetic resonance. In contrast, carbohydrate restriction (CR-L and CR-H) resulted in lower concentrations of medium very-low-density lipoprotein and small LDL particles compared to the high-carbohydrate groups. Plasma lecithin:cholesterol acyltransferase (LCAT) activity was decreased and cholesterol ester transfer protein activity was increased by dietary cholesterol, whereas carbohydrate restriction increased LCAT activity (P<.05). These findings are similar to those observed in humans, thus validating the use of adult guinea pigs to study lipid responses to carbohydrate restriction. The results also indicate that the atherogenicity of lipoproteins induced by high dietary cholesterol is attenuated by carbohydrate restriction in guinea pigs.

Should We Take High-Density Lipoprotein Cholesterol Levels at Face Value?

The inverse correlation between high-density lipoprotein (HDL) levels and cardiovascular disease has driven several investigators to target the increase in this lipoprotein to prevent atherosclerosis and its complications. However, many reports have demonstrated that the use of HDL cholesterol (HDL-C) levels as a means to prevent and treat atherosclerosis has mainly resulted in negative outcomes. These findings may help to increase our knowledge of HDL metabolism and its protective effect.There is evidence that the mechanism by which HDL-C levels are raised has a great impact on cardiovascular outcomes. When the increase in HDL-C levels is secondary to greater synthesis, a strong beneficial effect in the prevention of cardiovascular diseases is observed. Even small increases in HDL-C levels induce a marked reduction in cardiovascular events; this has been observed during treatment with fibrates. In contrast, when the increase in HDL-C levels is secondary to a reduction in HDL catabolism, unexpectedly, the opposite effects are usually noted. Even dramatic increases in HDL-C levels are not associated with better cardiovascular outcomes. In fact, these increases have been related to a greater number of cardiovascular-related deaths. This became clear from the results of trials that tested inhibitors of cholesteryl ester transfer protein (CETP). We suggest that increases in reverse cholesterol transport are more important than HDL-C levels. Strong evidence is provided by individuals that express apolipoprotein (apo)A-I Milano. These individuals have extremely low HDL-C levels due to greater catabolism of the lipoprotein. However, reverse cholesterol transport is increased in these individuals and, as a consequence, they have a low incidence of cardiovascular diseases.We reinforce that, in clinical practice, the currently recommended levels of HDL-C should still be a major target to be aimed for. However, in the research field, we emphasize the need to look for other methods to improve reverse cholesterol transport, irrespective of HDL-C levels.

Estenose do enxerto de veia safena magna reversa em revascularização arterial infrainguinal

OBJECTIVE: The aim of this study was to evaluate the prevalence of hemodynamically significant infrainguinal bypasses stenosis using reverse great saphenous vein graft. METHODS: From March of 2008 to March of 2009, 56 infrainguinal bypasses were performed with reverse great saphenous vein graft in 56 patients. On the 30th post-operative day, 32 out of 56 patients were submitted to vascular ultrasonography. The prevalence of significant graft stenosis was determined. In addition, the diagnosis of stenosis was related to the clinical and surgical characteristics of the patients. The variables analyzed at the moment of diagnosis were the localization of the graft stenosis, the risk factors associated with stenosis and the association of vascular ultrasonography findings with ankle brachial pressure index (ABI). RESULTS: The overall prevalence of significant graft stenosis was 48.4%. Out of the total number of observed stenosis, 19.4% were considered severe, and 29% mild or moderate. There was no significant association between the presence of significant stenosis and the following variables: gender, diabetes, hypertension, smoking, hipercholesterolemia, graft diameter, site of the distal anastomosis, and graft composition. There was a weak agreement between ABI and vascular ultrasonography in detecting stenosis in general (K = 0.30; CL95% 0.232 - 0.473; p = 0.018). However, there was a substantial agreement in detecting severe stenosis (K = 0.75; CL95% 0.655 - 0.811; p = 0.0001). CONCLUSION: There was a high prevalence of stenosis on the 30th post-operative day, mostly localized in the proximal half of the vein graft. There was no significant association of stenosis with clinical and surgical factors analyzed. ABI and vascular ultrasonography had weak agreement with the diagnosis of stenosis in general and an important agreement for the diagnosis of severe stenosis.

Stenosis of reverse great saphenous vein graft in infrainguinal arterial revascularization

OBJECTIVE The aim of this study was to evaluate the prevalence of hemodynamically significant infrainguinal bypasses stenosis using reverse great saphenous vein graft. METHODS From March of 2008 to March of 2009, 56 infrainguinal bypasses were performed with reverse great saphenous vein graft in 56 patients. On the 30th post-operative day, 32 out of 56 patients were submitted to vascular ultrasonography. The prevalence of significant graft stenosis was determined. In addition, the diagnosis of stenosis was related to the clinical and surgical characteristics of the patients. The variables analyzed at the moment of diagnosis were the localization of the graft stenosis, the risk factors associated with stenosis and the association of vascular ultrasonography findings with ankle brachial pressure index (ABI). RESULTS The overall prevalence of significant graft stenosis was 48.4%. Out of the total number of observed stenosis, 19.4% were considered severe, and 29% mild or moderate. There was no significant association between the presence of significant stenosis and the following variables: gender, diabetes, hypertension, smoking, hipercholesterolemia, graft diameter, site of the distal anastomosis, and graft composition. There was a weak agreement between ABI and vascular ultrasonography in detecting stenosis in general (K = 0.30; CL95% 0.232 - 0.473; p = 0.018). However, there was a substantial agreement in detecting severe stenosis (K = 0.75; CL95% 0.655 - 0.811; p = 0.0001). CONCLUSION There was a high prevalence of stenosis on the 30th post-operative day, mostly localized in the proximal half of the vein graft. There was no significant association of stenosis with clinical and surgical factors analyzed. ABI and vascular ultrasonography had weak agreement with the diagnosis of stenosis in general and an important agreement for the diagnosis of severe stenosis.