Nathalie Bergeron

Gender Difference in Postprandial Lipemia Importance of Visceral Adipose Tissue Accumulation

Insulin resistance, hyperinsulinemia, hypertriglyceridemia, and low HDL-cholesterol concentrations are common features of a plurimetabolic syndrome, which increases the risk of coronary artery disease. Although it has been proposed that the development of atherosclerosis through alterations in plasma lipid levels could be a postprandial phenomenon, most studies on gender differences in plasma lipoprotein-lipid concentrations have reported fasting levels. Therefore, the aim of our study was to examine the response of postprandial triglyceride-rich lipoproteins to a standardized meal in 63 men and 25 women. In addition to the measurement of fasting and postprandial plasma lipid levels, numerous physical and metabolic variables were assessed, including body composition by underwater weighing and body fat distribution by computed tomography. Although no gender difference was noted in total body fat mass, men were characterized by a preferential accumulation of abdominal adipose tissue as revealed by an increased waist circumference and a greater visceral adipose tissue accumulation (50% difference) compared with women (P<0.001). Men also showed a greater plasma triglyceride response (P<0.005) as well as increased postprandial insulin and free fatty acid levels compared with women (P<0.01). Visceral adipose tissue was significantly associated with the postprandial triglyceride response in both genders (men: r=0.49, P<0. 0001; women: r=0.43, P<0.05). Finally, when men and women were matched for visceral adipose tissue accumulation, the gender difference in postprandial plasma triglyceride response was eliminated. Thus results of the present study suggest that the well known gender difference in visceral adipose tissue accumulation is an important contributing factor involved in the exaggerated postprandial triglyceride-rich lipoprotein response noted in men compared with women.

Lack of effect of dietary conjugated linoleic acids naturally incorporated into butter on the lipid profile and body composition of overweight and obese men

BACKGROUND Dietary conjugated linoleic acid (CLA) is known to reduce atherosclerosis, plasma total and LDL-cholesterol concentrations, and body fat accumulation in several animal species. Of the few studies that investigated the effects of CLA supplementation in humans, all used commercially formulated oral supplements made from a mixture of CLA isomers. OBJECTIVE We compared the effects on plasma lipoproteins and body composition of the consumption of a modified butter naturally enriched with CLA (CLA-B: 4.22 g CLA/100 g butter fat) by the addition of sunflower oil to the diet of dairy cows with the consumption of a control butter (CON-B) that was low in CLA (0.38 g CLA/100 g butter fat). DESIGN In a crossover design study including an 8-wk washout period, 16 men [x +/- SD age: 36.6 +/- 12.4 y; body mass index (in kg/m2): 31.2 +/- 4.4] were fed each of the 2 experimental isoenergetic diets, providing 15% of energy as protein, 45% as carbohydrates, and 40% as lipids, of which >60% was derived from experimental fats, for 4 wk. RESULTS Consumption of the CLA-B diet induced a significantly (P < 0.05) smaller reduction in plasma total cholesterol and in the ratio of total to HDL cholesterol (-0.02 mmol/L and -0.00, respectively) than did consumption of the CON-B diet (-0.26 mmol/L and-0.34, respectively). Abdominal adipose tissue area measured by computed tomography showed no difference in accumulation of either visceral or subcutaneous adipose tissue after the 2 experimental diets. CONCLUSION These results suggest that a 10-fold CLA enrichment of butter fat does not induce beneficial metabolic effects in overweight or obese men.

Prolonged postprandial responses of lipids and apolipoproteins in triglyceride-rich lipoproteins of individuals expressing an apolipoprotein epsilon 4 allele.

The postprandial responses of apo B48, B100, E and lipids in triglyceride-rich lipoproteins (TRL) to a meal containing one-third of daily energy (39% fat calories) were compared in normolipidemic young men with apo E3/3 and apo E4/3 phenotypes. After the two groups consumed a diet rich in polyunsaturated fat for 15-29 d, their postabsorptive concentrations of TRL triglycerides, apo B48, and apo B100 were virtually identical, but their postprandial responses differed. In both groups, TRL apo B48 increased at 3 h but returned to postabsorptive values at 6 h only in the apo E3/3 group; in the apo E4/3 group the concentration of apo B48 at 6 h was 80% higher than postabsorptive values. TRL apo B100 also increased at 3 h in the two groups and fell to post-absorptive values at 6 h in the apo E3/3 group but remained 51% higher than postabsorptive concentrations in the apo E4/3 group; this response was closely coupled to that of TRL cholesterol and apo E. These observations suggest that clearance of intestinal and hepatogenous TRL remnants is impaired in young men with an apo E4/3 phenotype.

Saturated Fats Versus Polyunsaturated Fats Versus Carbohydrates for Cardiovascular Disease Prevention and Treatment

The effects of saturated fatty acids (SFAs) on cardiovascular disease (CVD) risk are modulated by the nutrients that replace them and their food matrices. Replacement of SFAs with polyunsaturated fatty acids has been associated with reduced CVD risk, although there is heterogeneity in both fatty acid categories. In contrast, replacement of SFAs with carbohydrates, particularly sugar, has been associated with no improvement or even a worsening of CVD risk, at least in part through effects on atherogenic dyslipidemia, a cluster of traits including small, dense low-density lipoprotein particles. The effects of dietary SFAs on insulin sensitivity, inflammation, vascular function, and thrombosis are less clear. There is growing evidence that SFAs in the context of dairy foods, particularly fermented dairy products, have neutral or inverse associations with CVD. Overall dietary patterns emphasizing vegetables, fish, nuts, and whole versus processed grains form the basis of heart-healthy eating and should supersede a focus on macronutrient composition.

Effect of a High-Fructose Weight-Maintaining Diet on Lipogenesis and Liver Fat

CONTEXT Consumption of high-fructose diets promotes hepatic fatty acid synthesis (de novo lipogenesis [DNL]) and an atherogenic lipid profile. It is unclear whether these effects occur independent of positive energy balance and weight gain. OBJECTIVES We compared the effects of a high-fructose, (25% of energy content) weight-maintaining diet to those of an isocaloric diet with the same macronutrient distribution but in which complex carbohydrate (CCHO) was substituted for fructose. DESIGN, SETTING, AND PARTICIPANTS Eight healthy men were studied as inpatients for consecutive 9-day periods. Stable isotope tracers were used to measure fractional hepatic DNL and endogenous glucose production (EGP) and its suppression during a euglycemic-hyperinsulinemic clamp. Liver fat was measured by magnetic resonance spectroscopy. RESULTS Weight remained stable. Regardless of the order in which the diets were fed, the high-fructose diet was associated with both higher DNL (average, 18.6 ± 1.4% vs 11.0 ± 1.4% for CCHO; P = .001) and higher liver fat (median, +137% of CCHO; P = .016) in all participants. Fasting EGP and insulin-mediated glucose disposal did not differ significantly, but EGP during hyperinsulinemia was greater (0.60 ± 0.07 vs 0.46 ± 0.06 mg/kg/min; P = .013) with the high-fructose diet, suggesting blunted suppression of EGP. CONCLUSION Short-term high-fructose intake was associated with increased DNL and liver fat in healthy men fed weight-maintaining diets.

Proprotein Convertase Subtilisin/Kexin Type 9 Inhibition A New Therapeutic Mechanism for Reducing Cardiovascular Disease Risk

Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays an important role in the regulation of cholesterol homeostasis. By binding to hepatic low-density lipoprotein (LDL) receptors and promoting their lysosomal degradation, PCSK9 reduces LDL uptake, leading to an increase in LDL cholesterol concentrations. Gain-of-function mutations in PCSK9 associated with high LDL cholesterol and premature cardiovascular disease have been causally implicated in the pathophysiology of autosomal-dominant familial hypercholesterolemia. In contrast, the more commonly expressed loss-of-function mutations in PCSK9 are associated with reduced LDL cholesterol and cardiovascular disease risk. The development of therapeutic approaches that inhibit PCSK9 function has therefore attracted considerable attention from clinicians and the pharmaceutical industry for the management of hypercholesterolemia and its associated cardiovascular disease risk. This review summarizes the effects of PCSK9 on hepatic and intestinal lipid metabolism and the more recently explored functions of PCSK9 in extrahepatic tissues. Therapeutic approaches that prevent interaction of PCSK9 with hepatic LDL receptors (monoclonal antibodies, mimetic peptides), inhibit PCSK9 synthesis in the endoplasmic reticulum (antisense oligonucleotides, siRNAs), and interfere with PCSK9 function (small molecules) are also described. Finally, clinical trials testing the safety and efficacy of monoclonal antibodies to PCSK9 are reviewed. These have shown dose-dependent decreases in LDL cholesterol (44%-65%), apolipoprotein B (48%-59%), and lipoprotein(a) (27%-50%) without major adverse effects in various high-risk patient categories, including those with statin intolerance. Initial reports from 2 of these trials have indicated the expected reduction in cardiovascular events. Hence, inhibition of PCSK9 holds considerable promise as a therapeutic option for decreasing cardiovascular disease risk.

ASSESSMENT OF POSTPRANDIAL LIPEMIA : NUTRITIONAL INFLUENCES

Recent reports have contributed new information on the influence of the size and spacing of fat-containing meals on processes related to fat digestion and absorption, lymphatic transport, and postprandial responses of plasma lipoproteins. The postabsorptive concentrations of plasma triglycerides and common polymorphisms of apolipoprotein B and apolipoprotein E exert important influences on postprandial lipoprotein responses. Attention to these characteristics of individuals and groups can facilitate interpretation of responses to meals containing different fatty acids and varying amounts of cholesterol. Additional evidence is accumulating that points to disease related abnormalities of postprandial lipoprotein metabolism related to clearance mechanisms for triglyceride-rich lipoproteins and processes related to reverse cholesterol transport.

The choice of a diet quality indicator to evaluate the nutritional health of populations

BACKGROUND The USA and Canada both want to reduce social health inequalities in their population. These two countries have recently begun a process of harmonization of their nutrient recommendations. OBJECTIVE To develop a standardized indicator to measure the impact of these recommendations on the health of different social groups in North America. The authors have compared three of the methods currently used for measuring overall diet quality for a population. DESIGN AND SETTING The three methods, adjusted to the 1990 Canadian nutrition recommendations, were used to analyse the Québec Nutrition Survey data collected by Santé Québec in 1990. RESULTS The authors found that the indicator developed by Kennedy and collaborators works best for analysing the Québec data. Moreover, it allows comparisons with the USA. Some questions, such as whether or not to add calories from alcohol consumption to the model and whether the indicators should be adjusted to the different cultures and specific population groups remain unanswered. CONCLUSIONS In order to determine the role of nutrition in social health inequalities, it is important to develop standard indicators that are suitable for monitoring the relationship between dietary recommendations and eating habits.

Endothelial lipase is associated with inflammation in humans.

The aim of this study was to investigate the extent to which inflammation is linked with plasma endothelial lipase (EL) concentrations among healthy sedentary men. Plasma C-reactive protein (CRP) concentrations were measured with a highly sensitive commercial immunoassay, plasma interleukin-6 (IL-6) concentrations were measured using a commercial ELISA, and plasma secretory phospholipase A2 type IIA (sPLA2-IIA) concentrations were measured using a commercial assay in a sample of 74 moderately obese men (mean body mass index, 29.8 ± 5.2 kg/m2). Plasma EL concentrations were positively correlated with various indices of obesity, fasting plasma insulin, and plasma CRP, IL-6, and sPLA2-IIA concentrations. Multiple regression analyses revealed that plasma CRP concentrations explained 14.5% (P = 0.0008) of the variance in EL concentrations. When entered into the model, LPL activity accounted for 16.1% (P < 0.0001) and plasma CRP concentrations accounted for 20.9% (P < 0.0001) of the variance in EL concentrations. The combined impact of visceral adipose tissue (VAT) and of an inflammation score on EL concentrations was investigated. Among subjects with high or low VAT, those having a high inflammation score based on plasma CRP, IL-6, and sPLA2-IIA concentrations had increased plasma EL concentrations (P = 0.0005). In conclusion, our data reveal a strong association between proinflammatory cytokines and plasma EL concentrations among healthy people with low or high VAT levels.

Influence of fish protein as compared to casein and soy protein on serum and liver lipids, and serum lipoprotein cholesterol levels in the rabbit

Serum and hepatic cholesterol and triglyceride levels, and serum lipoprotein cholesterol were investigated in rabbits fed fish protein as compared to casein and soy protein as part of a 20% protein, low fat, cholesterol-free, semi-purified diet. A nonpurified diet was used as a control. After a 28-day experimental period, rabbits fed casein developed hypercholesterolemia compared to those fed the soy protein diet. Serum cholesterol levels of rabbits fed fish protein was intermediate and not different from that of the casein or the soy protein group. However, serum triglycerides were higher in the fish group than in the casein group. Feeding of fish protein resulted in a reduction of hepatic cholesterol compared to casein, indicating no direct relationship between serum and hepatic cholesterol. In addition, fish protein induced a decrease of cholesterol in the low density lipoproteins (LDL) compared to casein and an increase of cholesterol in the high density lipoproteins (HDL) compared to casein and soy protein. Reduction in LDL-cholesterol (LDL-C) and elevation in HDL-cholesterol (HDL-C) caused a 10-fold decrease in the LDL-C/HDL-C ratio of fish protein fed rabbits compared to those fed casein. This ratio was similar to that observed with soy protein which was also lower than the ratio of the casein group. Thus, since the LDL-C/HDL-C ratio has been shown to be a good indicator of the atherosclerosis risk, these results suggest that fish protein, as well as soy protein, may reduce the risk of atherosclerosis in rabbits, compared to casein.