Previous studies on the relationship between the plasma insulin level, insulin sensitivity (SI), serum lipids, and lipoproteins have been performed predominantly in men. Therefore, we investigated whether there is a sex difference in the association of insulin level during an oral glucose tolerance test and SI with lipids and lipoproteins among normoglycemic men and women aged 53 to 61 years. SI was determined by the minimal model from the frequently sampled intravenous glucose tolerance test (IVGTT). There were no correlations between total cholesterol or low-density lipoprotein (LDL) cholesterol and insulin level or SI. High-density lipoprotein (HDL) cholesterol correlated inversely with fasting insulin (r = -.26, P < .05 in men; r = -.29, P < .01 in women) and 2-hour insulin (r = -.31, P < .01 in men; r = -.39, P < .001 in women) and positively with SI (r = .28, P = .05 in men; r = .43, P < .001 in women). Total and very-low-density lipoprotein (VLDL) triglycerides correlated positively with fasting insulin (r = .43, P < .001 in men; r = .42, P < .001 in women) and 2-hour insulin (r = .50, P < .001 in men; r = .31, P < .01 in women) and inversely with (r = -.49, P < .001 in men; r = -.40, P < .001 in women). In multiple regression analyses including age, body mass index (BMI), waist to hip ratio, 2-hour glucose, fasting or 2-hour insulin, and SI, only BMI was associated with HDL cholesterol level in men.(ABSTRACT TRUNCATED AT 250 WORDS)

The extent to which an individual maintains his position relative to the rest of the population is called tracking. The objective of this study was to examine the effect of the apolipoprotein E (apoE) phenotype on the tracking of serum cholesterol and lipoproteins from birth to the age of 11 y. In a longitudinal follow-up study of healthy children, concentrations of total serum cholesterol and triglyceride were determined at birth (n = 193), and at the ages of 2 (n = 192), 4 (n = 192), 6 (n = 190), 9 (n = 188), and 12 mo (n = 196), and 5 (n = 162) and 11 y (n = 153). Concentrations of total HDL, HDL2, and HDL3, VLDL, and LDL cholesterol were determined at 2, 6, 9, and 12 mo (n = 36), and 5 (n = 162) and 11 y (n = 153). The apoE phenotype was determined in 151 children. The children had the following apoE phenotypes: 4 had type 4/4 and 40 type 3/4 (group apoE4), 94 had type 3/3 (group apoE3), and 11 had type 2/3 and 2 type 2/4 (group apoE2). The correlation coefficients for total cholesterol levels during childhood compared with the level at 11 y of age were: 0.03 at birth, 0.26 (p < 0.001) at 2 mo, 0.24 (p < 0.001) at 4 mo, 0.24 (p < 0.001) at 6 mo, 0.28 (p < 0.001) at 9 mo, 0.41 (p < 0.001) at 12 mo, and 0.60 (p < 0.001) at 5 y. When the children were divided into three groups according to their apoE phenotypes, these three groups had the following correlation coefficients at 4 mo, 12 mo, or 5 y of age compared with the level at the age of 11 y; group apoE2: r = 0.65 (p < 0.01), r = 0.59 (p < 0.01), and r = 0.72 (p < 0.01); group apoE3: r = 0.27 (p < 0.01), 0.43 (p < 0.001), and r = 0.64 (p < 0.001); and group apoE4: r = 0.14 (p = NS), r = 0.33 (p < 0.05), and 0.42 (p < 0.01). The apoE phenotype also strongly influenced the tracking of the LDL cholesterol levels; the correlation coefficients between 5 and 11 y of age were for group apoE2 r = 0.84 (p < 0.001), for group apoE3 r = 0.70 (p < 0.001), and for group apoE4 r = 0.37 (p < 0.05). Our results indicate that the apoE phenotype strongly influences the tracking of lipids. The children having apoE 2/3, 2/4, and 3/3 phenotypes maintained their relative cholesterol and lipoprotein levels better than the others throughout the first 11 y of age. Because the apoE phenotype strongly affects the tracking of serum cholesterol, the usefulness of cholesterol screening in predicting future cholesterol values should be analyzed, keeping the apoE phenotype in mind.

OBJECTIVE

Adiponectin is an adipokine highly and specifically expressed by adipose cells with antiatherogenic and antiinflammatory activities. The aim of the present study was to evaluate plasma adiponectin concentration in patients with primary hypertriglyceridemia and its relationship with metabolic parameters.

RESULTS

Male patients with primary hypertriglyceridemia and without the metabolic syndrome (n=22) were compared with normotriglyceridemic individuals (n=25). Plasma adiponectin concentration was measured by standardised enzyme-linked immunosorbent assay. Body mass index, waist circumference, glucose, insulin and non-esterified fatty acid levels, lipoprotein profile, and CETP activity were evaluated. Adiponectin levels were significantly decreased in hypertriglyceridemic patients in comparison with normotriglyceridemic subjects (4292+/-1717 vs. 6939+/-3249 ng/ml, p<0.005, respectively). Adiponectin was negatively associated with glucose (r=-0.44, p<0.01), insulin (r=-0.37, p<0.01), HOMA (r=-0.40, p<0.01), triglycerides (r=-0.36, p<0.01), VLDL-C (r=-0.34, p<0.05), and CETP (r=-0.47, p<0.001). Positive and significant correlations were observed with QUICKI (r=0.49, p<0.001) and HDL-C (r=0.33, p<0.05). In the multiple linear regression analysis, considering waist circumference, QUICKI, Log-triglycerides, HDL-C, and CETP as independent variables, Log-adiponectin showed a positive correlation with QUICKI, with an r(2)=0.229 and p<0.001. Therefore, the independent variable QUICKI explained the 23% of the variance in Log-adiponectin concentration.

CONCLUSIONS

We found low adiponectin levels in a population of primary hypertriglyceridemic men without the metabolic syndrome and an independent relationship between adiponectin concentration and insulin resistance. A reduction in insulin sensitivity and its impact on adiponectin concentration could be linked to high non-esterified fatty acid levels, increased triglyceride synthesis in the liver and impaired catabolism of triglyceride-rich lipoproteins.

BACKGROUND

Although LDL resistance to copper-induced oxidation is a time-honoured method, how it is modulated by the physiologic variability of lipid phenotype and what influences the protective action of homologous HDL and exogenous alanine is still unclear.

METHODS

In 159 subjects without severe dyslipidemias, LDL resistance to copper-induced oxidation (lag phase) was measured under standardised conditions, with alanine and with autologous HDL.

RESULTS

Lag phase was normally distributed and averaged 68+/-10 min (range: 40-105 min). Both VLDL-triglycerides (37+/-5, 52+/-7, 59+/-7, 53+/-5 mg/dl, p<0.05) and LDL-triglycerides (27+/-2, 27+/-1, 30+/-2, 35+/-3 mg/dl, p<0.01) increased across quartiles of lag phase. The relative LDL enrichment in triglycerides (triglycerides percent or triglycerides/cholesterol ratio) was strongly related to lag phase (r=0.29 and r=0.31, p<0.0005 for both) independently of age, gender, BMI, and presence of diabetes or hypertension. The protective effect of HDL was variable (+42+/-18 min) and largely dependent on the capacity of HDL to resist oxidation (r=0.69, p<0.0001). Alanine induced a rather constant lag phase prolongation (+32+/-7 min) that was weakly related only to baseline lag phase (r=0.17, p<0.05).

CONCLUSIONS

Relative triglyceride abundance protects LDL from ex-vivo oxidation, HDL particles protect LDL mainly through substrate dilution and alanine probably through a direct anti-oxidant effect.

African-American females with type 2 diabetes mellitus are at greater risk for cardiovascular morbidity and mortality when compared to diabetic African-American males and whites. To explain the gender differences in morbidity and mortality secondary to cardiovascular diseases (CVD) associated with type 2 diabetes mellitus (DM) in middle-aged, African Americans (AA), we have postulated that increased incidence of CVD in AA females could be ascribed in part to greater clustering of pre-existing CVD risks when compared to their AA male counterparts. We have therefore investigated the metabolic and anthropometric risk factors for CVD in an AA population who are genetically at greater risk for type 2 DM. We studied 84 healthy first-degree relatives of AA patients with type 2 diabetes, 42 males and 42 females with a mean age 42.5+/-8.4 years, age range 25-65 years, matched for age and waist-to-hip circumference ratio (WHR) in order to determine the impact of body fat distribution pattern on CVD risks. A standard oral glucose tolerance test (OGTT) and an insulin-modified frequently sampled intravenous glucose tolerance (FSIGT) test were performed for each subject. In addition, lipid and lipoprotein levels, anthropometric parameters, blood pressure, sociodemographics and physical activity levels were obtained for each subject. Insulin sensitivity index (Si) and glucose-dependent glucose disposal (Sg) were determined using Bergman's Minimal Model method. Hepatic insulin extraction (HIE) was calculated as the molar ratio of basal and postprandial c-peptide and insulin concentrations. Mean age, annual income and percent participation in physical activity did not differ between genders. Despite the identical WHR, body mass index (BMI) (34.8+/-7.5 vs 30.3+/-6.7 kg/m2, P=0.005), and % body fat (43.8+/-7.3 vs 28.1+/-7.7%, P=0.001) were greater in females than males, respectively. The systolic blood pressure(SBP), but not the diastolic blood pressure (DBP), was significantly lower in our female vs male group. Mean fasting and 2-hour postprandial serum glucose and insulin levels were significantly greater in the female group. In contrast, the corresponding serum c-peptide levels were not significantly different between the groups. Thus, the basal and postprandial hepatic insulin extractions (HIE) were 30% lower in the females than in the males. The mean absolute levels of cholesterol (C), low density lipoprotein-C (LDL-C), very low-density lipoprotein-C (VLDL-C), high-density lipoprotein-C (HDL-C), and triglycerides were not significantly different between the genders. Mean Si was significantly lower in the females when compared to males (Si, 1.62+/-1.66 vs 2.45+/-1.81 x 10(-4) x min(-1) (microU/ml)(-1), P=0.03). The mean Sg was identical in both groups (2.66+/-1.99 vs 2.67+/-1.35 x 10(-2) x min(-1), P=0.97). We found no significant correlations between Si and SBP and DBP, WHR, or lipids and lipoproteins in the females. In contrast, Si correlated significantly with WHR (R=-0.346, P=0.05), HDL-C (R=0.310, P=0.05), but not with BP, LDL-C, and triglyceride levels in the males. We conclude that nondiabetic African-American females manifest several metabolic and anthropometric risk factors for cardiovascular diseases that precede the disease by decades. Therefore, obese AA females with family history of type 2 DM should be particularly targeted for diabetes and CVD risk prevention programs using effective and practical weight reduction modalities.

OBJECTIVE

Atherosclerosis, the root cause of cardiovascular disease (CVD), has a number of risk factors-some modifiable and some not. CVD increases in women particularly during the postmenopausal period. Small dense low-density lipoprotein (sdLDL), a subclass of LDL, is an important determinant of atherosclerosis in postmenopausal women. Paraoxonase1 (PON1) is a high-density lipoprotein (HDL)-associated enzyme that prevents oxidative modifications in LDL and HDL. With this background, we studied the sdLDL-C, PON1 and lipid profile in postmenopausal women to compare between quality and quantity of LDL.

METHODS

We studied 80 pre- and postmenopausal women (40/group). The following parameters were studied: lipid profile, sdLDL-C and PON1 levels. With proper statistical tools the correlation between these parameters was studied.

RESULTS

Postmenopausal women, in comparison with premenopausal women, have significantly increased levels of serum triglycerides and sdLDL-C and very-low-density lipoprotein cholesterol (VLDL-C) and significantly decreased levels of HDL-C and PON1. PON1 activity was negatively correlated with age, TC, TG, LDL-C and sdLDL-C (r = -0.574, -0.119, -0.226, -0.473 and -0.455, respectively) and positively correlated with HDL-C (r = 0.368), whereas sdLDL-C was positively correlated with age, TC, TG, LDL-C (r = 0.633, 0.485, 0.561 and 0.705, respectively) and negatively with HDL-C (r = -0.235). Stepwise multiple regression analysis demonstrated HDL-C and menopausal status as the best determinant for PON1 (R(2) = 0.320, p < 0.05) and menopausal status, LDL-C, TG, and TC were the best determinants for sdLDL-C (R(2) = 0.606, p < 0.05).

CONCLUSIONS

The results of the present study suggest quality, i.e., sdLDL-C, is more important than only LDL-C levels. Similarly, decrease in PON1 and increase in sdLDL-C go hand in hand. This shows that antioxidant capacity is compromised with a qualitative downfall in lipoproteins in postmenopausal women.

The concentration of high density lipoproteins (HDL) is related to the catabolism of triglyceride-rich lipoproteins. In order to elucidate the mechanisms by which alcohol increases plasma HDL levels we measured the turnover kinetics of very low density lipoprotein (VLDL) triglycerides in 10 alcoholic men without liver disease and in nonalcoholic control men matched for age, weight and plasma VLDL triglyceride level. The study was repeated in the alcoholics after a 2-week abstinence period. The alcoholic men had elevated HDL cholesterol but reduced low density lipoprotein (LDL) cholesterol as compared to the controls. The fractional catabolic rate and the total turnover (production) rate of VLDL triglycerides were both significantly increased (P less than 0.05) in the alcoholic men before abstinence. After withdrawal of alcohol both the synthetic rate and the catabolic rate of VLDL triglycerides returned to normal and the HDL (HDL2 and HDL3) cholesterol fell. The per cent decrease in HDL2 cholesterol during abstinence was positively correlated to the respective fall of VLDL triglyceride fractional catabolic rate (r = +0.51). The results suggest that the absence of hypertriglyceridemia and the elevated levels of HDL in regular alcohol users may be partly based on increased metabolic clearance of VLDL particles and on subsequent accelerated transfer of the VLDL surface components to HDL.

The serum concentrations of selenium in 13 healthy children and 27 children with type 1 diabetes mellitus were evaluated in relation to serum lipoprotein and apolipoprotein concentrations. In healthy children a correlation was found between serum selenium and both serum cholesterol (r = 0.56; p less than 0.05) and serum triglycerides (r = 0.56; less than 0.05) and their low-density lipoprotein (LDL) + very low-density lipoprotein (VLDL) fractions (r = 0.60 and 0.56 respectively; p less than 0.05), but not their high-density lipoprotein fractions. Associations were also found between selenium and apolipoproteins, especially A II and C II (r = 0.57; p less than 0.05). In diabetic children serum selenium was significantly correlated with apolipoproteins A II and Apo C II, but not with any lipoprotein or lipid or any of their fractions. This study supports the hypothesis that serum selenium is an integral part of the defence system against degradation products associated with LDL and VLDL in young healthy humans. These associations were not found in diabetes, which might suggest that the defence system against lipid peroxidation is less effective in this disease.

BACKGROUND

Abnormal lipid profiles are a characteristic feature of persons with chronic conditions in which the diabetic populations are recognized as the dominant group, regardless of gender and ethnicity worldwide. This study was conducted to identify and evaluate the abnormalities of serum lipid profiles in both nondiabetic and diabetic persons.

METHODS

This study was a case-control investigation conducted between 2013 and 2015. The study enrolled 266 patients from the North Central and South West Regional Health Authorities of Trinidad. Of the 266 patients recruited, 126 were diabetic and 140 were nondiabetic.

RESULTS

Our study observed that dyslipidemia was present among the nondiabetic populations as the nondiabetics had 55 women and 20 men with high cholesterol, 22 women and 14 men with high triglyceride (TG), 30 women and 25 men with low high-density lipoprotein cholesterol (HDL-C), 42 women and 21 men with high low-density level-cholesterol (LDL-C), 13 women and 8 men with high very low-density lipoprotein (VLDL), and also 30 women and 11 men with body mass index (BMI) over 30 kg/m2. We also observed that diabetic women had significantly lower TGs (P = 0.019) and higher HDL-C (P = 0.001) and LDL (P = 0.003) when compared with the diabetic men. In addition, the nondiabetic females also had higher HDL-C (P = 0.045) when compared to their male counterparts. Both diabetic and nondiabetic women exhibited significantly higher BMI of P = 0.000. A negative correlation was obtained among TGs and HDL (r = -0.356, n = 83, P = 0.001) and a positive correlation was observed among LDL and HDL (r = 0.230, n = 86, P = 0.035).

CONCLUSIONS

This study observed the incidences in the abnormalities of serum lipid profiles in both nondiabetic and diabetic persons. It also presents the high occurrence of nondiabetic women with dyslipidemia as they presented with high cholesterol, high TG, low HDL-C, and high VLD-L with BMI over 30 kg/m2.

The aim of this investigation was to analyse the influence of the number of meals per day on a range of cardiovascular risk factors and on the energy and nutrient intakes of a group of elderly people. The participants in this study were 150 elderly people (64 men and 86 women) from Madrid. Food intake was followed over a period of 5 days. "Precise individual weighing" was used to determine the intake of institutionalized subjects (n = 58) whilst "food intake records" were used to register the same for independent subjects (n = 92). The nutrient and energy intake of the studied population was then determined from these data. The number of meals taken was also recorded. Serum cholesterol and triacylglycerol levels were determined using enzymatic methods. In this population, the meal most frequently omitted was breakfast. No subject took only one meal per day, though 7.4% took only two. 56.6% took three meals and 36% took four. No subject took more than four meals per day. As the number of meals taken increased, so too the covering of theoretical energy expenditure, and the intakes of a range of nutrients became closer to those recommended e.g. proteins, fibre, vitamin C, thiamin, riboflavin, calcium, magnesium and iodine. As the number of meals taken per day increased, carbohydrate intake (in g/1000 Kcal and as % of energy) also increased, and approached recommended levels more closely. As observed in other studies, blood cholesterol levels were seen to be negatively correlated with increasing number of meals (r = -0.2297, p < 0.05). Further, those subjects who distributed their food intake more evenly throughout the day showed lower serum cholesterol (p < 0.05). VLDL-cholesterol (p < 0.05) and triacylglycerol levels (p < 0.05). The results favour the distribution of energy intake over the day as a method of improving nutritional status and as a factor that might improve blood lipid profiles.

Endothelium-derived relaxing factor (nitric oxide: NO) may provide an endogenous defence against atherosclerosis which impairs endothelium-dependent vascular relaxation. Atherosclerosis development is inhibited in cholesterol fed human apo A-I transgenic rabbits (Duverger, N., Circulation, 1996, 94, 713-717). We investigated if endothelium-dependent vascular relaxation is modified in human apo A-I transgenic rabbits by testing in vitro endothelium-dependent receptor-dependent vascular relaxation to acetylcholine and endothelium-dependent receptor-independent vascular relaxation to A23187 of abdominal aorta, precontracted with phenylephrine, in human apo A-I transgenic rabbits (n=4) versus non transgenic littermates (n=4). Endothelium-independent vascular relaxation was investigated with sodium nitroprusside. Vascular precontraction to phenylephrine was significantly increased in human apo A-I transgenic rabbits (p<0.05) while endothelium-independent vascular relaxation to nitroprusside was similar between human apo A-I transgenic rabbits and control rabbits. Endothelium-dependent receptor-dependent and receptor-independent vascular relaxations were reduced in human apo A-I transgenic rabbits (p<0.05). Maximum endothelium-dependent receptor-dependent vascular relaxation was negatively correlated with HDL-cholesterol and total apo A-I (rabbit+ human) plasma levels (r=0.87 and 0.86, p=0.01, respectively) but not with atherogenic plasma lipid (VLDL-cholesterol, LDL-cholesterol, VLDL+LDL cholesterol, triglycerides, apolipoprotein B) levels. These results suggest that the transgenesis of human apo A-I in rabbits impairs signal transduction of endothelial NO synthesis.

BACKGROUND

Androgens and insulin may contribute to increased sebum production in the pathogenesis of acne vulgaris.

OBJECTIVE

We investigated the association between serum desnutrin levels and acne vulgaris in the pathogenesis of insulin resistance.

METHODS

25 patients presenting with acne vulgaris and 25 control subjects participated in this study. Fasting blood glucose, triglycerides, LDL, VLDL, HDL, total cholesterol, insulin, C-peptide and thyroid function tests were measured. The homeostasis model assessment of insulin resistance (HOMA-IR) was used to calculate insulin resistance. Desnutrin levels were determined by enzyme-linked immunosorbent assay (ELISA) according to the manufacturer's protocol.

RESULTS

Patients with acne vulgaris had a mean serum desnutrin level of (8.83 ± 1.13 μIU/mL), which was statistically significantly lower in the control group (10:58 ± 3.43 μIU/mL). In patients with acne vulgaris the serum glucose levels, insulin levels and HOMA-IR values (87.92 ± 7:46 mg/dL, 11.33 ± 5.93 μIU/mL, 2.49 ± 1.40, respectively) were significantly higher than the control group (77.36 ± 9.83 mg/dL, 5.82 ± 2.68 μIU/mL, 1.11 ± 0.51, respectively) (p = 0.01, p<0.001, p<0.001, p<0.001, respectively).

CONCLUSIONS

Full cohort (patients and controls) evaluation revealed a negative correlation between the serum glucose and desnutrin levels (r = -0.31, p<0.05). A positive correlation was found between insulin and desnutrin levels (r = 0.42, p<0.001). In patients with acne vulgaris, as a result of increased levels of serum glucose and insulin, the function of desnutrin was suppressed, perhaps contributing to insulin resistance.

The effect of a bile acid sequestrant, cholebine (3 g/day), on plasma lipoprotein subfractions was investigated in 16 patients with type II hyperlipoproteinemia. Activities of low density lipoprotein (LDL)-receptor and activities of lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) were assayed to address the mechanism of cholebine-induced changes in plasma lipoprotein subfractions. Twelve weeks of treatment with cholebine reduced plasma levels of total cholesterol (TC) and LDL-cholesterol (C) by 8.3 +/- 8.1% (mean +/- S.D.) and 14.4 +/- 11.9%, respectively (P < 0.001), but did not affect plasma levels of high density lipoprotein (HDL)-C. Cholebine significantly reduced plasma levels of LDL1-C (1.019 < d < 1.045) by 22.9 +/- 18.9% (P < 0.001) but did not affect plasma levels of very low density lipoprotein (VLDL)-C, intermediate density lipoprotein (IDL)-C, LDL2-C (1.045 < d < 1.063), HDL2-C, and HDL3-C (d>> 1.125). Gradient polyacrylamide gel electrophoresis (PAGE) revealed that cholebine reduced large LDL in plasma but had almost no effects on small LDL and HDL subfractions. Cholebine did not alter the activities of LCAT and CETP. LDL-receptor activities of cultured lymphocytes negatively correlated with the reduction in plasma levels of LDL-C (r = -0.500, P < 0.05), IDL-C (r = -0.581, P < 0.02), and LDL1-C (r = -0.610, P < 0.01), respectively. Thus, cholebine seems to reduce further the plasma levels of IDL and large, light LDL in patients with lower LDL-receptor activities. We conclude that cholebine only reduces plasma levels of large, light LDL. This may be due to the stimulation of hepatic LDL-receptor activity.

Plasma lipoprotein and apoprotein (apo) A-I, A-II and B concentrations and post-heparin plasma lipoprotein lipase (LPL) activity and mass were measured in 13 children with congenital nephrotic syndrome of the Finnish type (CNF) six months after renal transplantation to determine whether the severe lipid abnormalities documented prior to and during peritoneal dialysis would normalize. Plasma total triglyceride decreased by 52% (p < 0.001), VLDL triglyceride by 55% (p < 0.01) and total cholesterol by 17% (p < 0.01). HDL cholesterol increased by 51% (p < 0.001), whereas no significant change was observed in LDL cholesterol. Despite these improvements, plasma lipoprotein concentrations were still abnormal after transplantation. Total (p < 0.01) and VLDL triglyceride (p < 0.05) as well as total (p < 0.01), VLDL (p < 0.01) and LDL cholesterol (p < 0.01) were higher than in control children. HDL cholesterol normalized. Plasma apo A-I and A-II concentrations were normal, but the apo B concentration remained high (p < 0.01). Post-heparin LPL activity and mass were normal (25.0 +/- 9.1 mumol FFA/ml/h and 227.2 +/- 88.4 ng/ml). The mean cyclosporine dose correlated positively with the serum creatinine concentration (r = +0.72, p < 0.01). Positive correlations were also observed between total (r = +0.68, p < 0.05) and VLDL triglyceride (r = +0.62, p < 0.05) and the serum creatinine concentrations. We conclude that renal transplantation substantially improves the triglyceride and cholesterol abnormalities in CNF but significant abnormalities still persist.

The relationships between VLDL concentrations and composition and changes in hepatic lipase and lipoprotein lipase activities were determined in rats, during the consumption of two low protein diets (2% casein or 5% gluten) (protein malnutrition) for 28 d, followed by the refeeding of a balanced diet for 14 d (15% casein) (refeeding). A control group was fed 15% casein for 42 d. In the control group, total lipolytic activity increased with age (r = 0.83, P < 0.001), whereas in both depleted groups, this activity remained low and stable throughout the period of protein malnutrition. At d 28 of protein malnutrition, plasma total lipolytic activities were significantly reduced in both depleted groups, (P < 0.05); hepatic lipase values represented 23% of the control value and lipoprotein lipase activity was about 11% of the control value. Moreover, lipid supply was even more dramatically diminished by the strong reduction in plasma VLDL concentration in both depleted groups. At d 14 of refeeding, lipoprotein lipase activities remained low in both depleted groups. Hepatic lipase activity was similar in the control and casein groups, but significantly higher in the gluten group. The VLDL composition varied significantly with each type of protein malnutrition and could be attributable to the different low levels of plasma VLDL-apolipoprotein C of rats fed both depleted protein diets, which involve an inhibiting or activating effect on lipoprotein lipase activity. Therefore, our results indicated that both protein-deficient diets investigated may diminish fatty acid supply in the various tissues involved.

Plasma lipid concentrations, lipoprotein composition, and glucose dynamics were measured and compared between mares fed diets containing added water, corn oil (CO), refined rice bran oil (RR), or crude rice bran oil (CR) to test the hypothesis that rice bran oil lowers plasma lipid concentrations, alters lipoprotein composition, and improves insulin sensitivity in mares. Eight healthy adult mares received a basal diet fed at 1.5 times the DE requirement for maintenance and each of the four treatments according to a repeated 4 x 4 Latin square design consisting of four 5-wk feeding periods. Blood samples were collected for lipid analysis after mares were deprived of feed overnight at 0 and 5 wk. Glucose dynamics were assessed at 0 and 4 wk in fed mares by combined intravenous glucose-insulin tolerance tests. Plasma glucose and insulin concentrations were measured, and estimated values of insulin sensitivity (SI), glucose effectiveness, and net insulin response were obtained using the minimal model. Mean BW increased (P = 0.014) by 29 kg (range = 10 to 50 kg) over 5 wk. Mean plasma concentrations of NEFA, triglyceride (TG), and very low-density lipoprotein (VLDL) decreased (P < 0.001) by 55, 30, and 39%, respectively, and plasma high-density lipoprotein and total cholesterol (TC) concentrations increased (P < 0.001) by 15 and 12%, respectively, over 5 wk. Changes in plasma NEFA (r = 0.58; P < 0.001) and TC (r = 0.44; P = 0.013) concentrations were positively correlated with weight gain over 5 wk. Lipid components of VLDL decreased (P < 0.001) in abundance over 5 wk, whereas the relative protein content of VLDL increased by 39% (P < 0.001). Addition of oil to the basal diet instead of water lowered plasma NEFA and TG concentrations further (P = 0.002 and 0.020, respectively) and increased plasma TC concentrations by a greater magnitude (P = 0.072). However, only plasma TG concentrations and VLDL free cholesterol content were affected (P = 0.024 and 0.009, respectively) by the type of oil added to the diet. Mean plasma TG concentration decreased by 14.2 mg/dL over 5 wk in the CR group, which was a larger (P < 0.05) decrease than the one (-5.3 mg/dL) detected in mares that received water. Consumption of experimental diets lowered S(I), but glucose dynamics were not affected by oil supplementation. Addition of oil to the diet altered blood lipid concentrations, and supplementation with CR instead of water specifically affected plasma TG concentrations and VLDL free cholesterol content.

The specific components of soy responsible for its beneficial effects on plasma lipids are unknown. Golden Syrian F(1)B Hybrid hamsters (75 male, 74 female) were evaluated for the effect of dietary soy and soy isoflavones on plasma lipids. They were fed the following diets for 16 wk: casein/lactalbumin (C/L), soy protein with isoflavones [Soy(+)], soy protein with isoflavones removed [Soy(-)], Soy(-) plus isoflavone extract (IF), and C/L + IF. At necropsy, plasma total cholesterol, HDL cholesterol (HDLC), LDL + VLDL cholesterol (LDL + VLDLC), isoflavones, and uterine and accessory gland weights were measured. Male hamsters fed the three soy-containing diets had lower LDL + VLDLC concentrations than those fed the two C/L diets (P < 0.01), and those fed Soy(-) + IF did not differ from those fed Soy(+). In females, diet did not affect plasma LDL + VLDLC concentration. Females fed Soy(+) or Soy(-) had higher HDLC (P < 0.05) than those fed C/L. HDLC was not affected by diet in males. Due to higher equol production (P < 0.01), males had greater plasma isoflavone concentrations (P < 0.01) than females. There was a positive association between plasma total isoflavones and LDL + VLDLC (r = 0.65, P < 0.05) in females. These data suggest gender differences in plasma lipid and isoflavone responses to soy- based diets in Syrian F(1)B Hybrid hamsters, which offer an opportunity to explore effects of sex hormones on isoflavone metabolism and the effects of isoflavones on lipid metabolism.

In 2019 ∼ 463 million people globally were diabetes mellitus (DM), with China (25.1%), India (16.6%), and the United States (6.69%) representing nearly 50% of that total. The primary objectives of this exploratory study were to assess the safety and potential efficacy of Nigella sativa and fenugreek seed supplemented chapatis in overweight (OW) and type 2 DM subjects. Forty subjects (15/OW; 9/DM; 16/DM/OW) consumed two chapatis twice a day 6 days/week for a daily dose of 5.45 g of an N. sativa/fenugreek combination over 12 weeks with no changes in lifestyle or medications. Anthropometric, glycemic, and vascular variables were recorded at baseline and after 6 and 12 weeks. Glycated hemoglobin (HbA1c), plasma lipids, and complete metabolic profile were measured at baseline and termination. Compliance, estimated during twice-daily individual delivery of precooked chapatis, was 100%, with no significant adverse effects. At termination, body weights, body mass index, waist and hip circumferences, index of central obesity, HbA1c, fasting blood glucose, 2-h postprandial blood glucose, estimated average glucose over 12 weeks, total cholesterol (TC), non-high density lipoprotein (HDL) cholesterol, very low density lipoprotein (VLDL), and triglycerides (TG) were decreased (P < .05) over all subjects. Subjects with HbA1c ≥7.0 exhibited greater improvements in all glycemic variables than HbA1c <7.0 subjects. In addition, the decrease in HbA1c was positively correlated with decreases in (1) hepatic enzymes alkaline phosphatase (r = 0.301, P = .0067) and aspartate transaminase (r = 0.277, P = .0129), (2) systolic blood pressure (r = 0.388, P = .0004), and (3) number of diagnostic metabolic syndrome criteria exhibited per subject (r = 0.391, P = .0005), cardiovascular risk score (CRS) (r = 0.281, P = .0115), and hepatic steatosis index (HSI) (r = 0.223, P = .0467). Atherogenic and diabetogenic indexes TC/HDL, low density lipoprotein/HDL, VLDL/HDL, and TG/HDL were all decreased (P < .05). Among all subjects, improvement (P < .05) was seen in CRS (-10.7%), fatty liver index (-19.8%), lipid accumulation product (-13.8%), and HSI (-7.53%). N. sativa/fenugreek supplemented chapatis present a safe and seamless dietary modification to address cardiometabolic risk.

<st<em>r</em>ong class="sub-title"> Keywo<em>r</em>ds: </st<em>r</em>ong> Nigella sativa; T<em>r</em>igonella foenum-g<em>r</em>aecum; hepatic steatosis; obesity; type 2 diabetes.

Very-low-density lipoprotein (VLDL) contributes to the buildup of atherosclerotic plaque in the arteries and can lead to coronary heart disease. In clinical laboratory testing, the cholesterol content of VLDL (VLDL-C) cannot be assessed directly by the enzymatic colorimetric assay as it can for other lipoproteins, due to lack of a specific sample pretreatment technique. VLDL concentration relies on analyzing the endogenous triglycerides (TGs) bound in its particles and then converting to the VLDL-C estimate TGs/5. This estimation is valid for at least 12 h-fasted serum when exogenous TGs attached to chylomicrons (CMs) have been cleared from the circulation. A quartz crystal microbalance (QCM)-based sensor was generated using biomimetic sensing elements as a molecularly imprinted polymer (MIP) to directly measure actual VLDL. A novel VLDL-MIP was synthesized using methacrylic acid (MAA) and N-vinylpyrrolidone (VP) in the ratio 1:1 (v/v) as functional monomers in the presence of N, N'-(1,2-dihydroxyethylene) bis(acrylamide) (DHEBA) as a crosslinking agent. The VLDL-MIP sensor showed high sensitivity with a linear response from 2.5 mg dL^-1 to 100 mg dL^-1 of VLDL-C with a limit of detection at 1.5 mg dL^-1. Recoveries of 96-103% were achieved when the VLDL-MIP sensor was used for VLDL assessment at 38-71 mg dL^-1 concentrations. Repeatability and reproducibility of the sensor were very good with coefficients of variation at 1.63-4.74% and 4.25-9.04%, respectively. The sensor demonstrated low cross-reactivity with other lipoproteins; 6-7% of low-density lipoprotein (LDL) signals, 2-4% high-density lipoprotein (HDL), and 1% CMs compared to the signal of VLDL. Sensor results for 12 h-fasted serum and non-fasted serum correlated well with VLDL estimates TGs/5, with coefficients of determination (R²) at 0.9967 and 0.9932, respectively. This new sensor offers a new strategy for direct VLDL assessment from non-fasted serum without other sample pretreatment steps than dilution.

Keywords: Molecularly imprinted polymers; Non-fasted serum; Quartz crystal microbalance; Sensor; Very-low-density lipoprotein.

Lipoproteins play a key role in regulating plasma and tissue levels of cholesterol. Apolipoprotein B (apoB)-containing lipoproteins, including chylomicrons, very-low density lipoprotein (VLDL) and low-density lipoprotein (LDL), serve as carriers of triglycerides and cholesterol and deliver these metabolites to peripheral tissues. In contrast, high-density lipoprotein (HDL) mediates Reverse Cholesterol Transport (RCT), a process by which excess cholesterol is removed from the periphery and taken up by hepatocytes where it is metabolized and excreted. Anti-atherogenic properties of HDL have been largely ascribed to apoA-I, the major protein component of the lipoprotein particle. The inflammatory response associated with atherosclerosis and ischemia-reperfusion (I-R) injury has been linked to the development of mitochondrial dysfunction. Under these conditions, an increase in reactive oxygen species (ROS) formation induces damage to mitochondrial structural elements, leading to a reduction in ATP synthesis and initiation of the apoptotic program. Recent studies suggest that HDL-associated apoA-I and lysosphingolipids attenuate mitochondrial injury by multiple mechanisms, including the suppression of ROS formation and induction of autophagy. Other apolipoproteins, however, present in lower abundance in HDL particles may exert opposing effects on mitochondrial function. This chapter examines the role of HDL-associated apolipoproteins and lipids in the regulation of mitochondrial function and bioenergetics.

Bile acids (BAs) are essential for the absorption of lipids. BA synthesis is inhibited through intestinal farnesoid X receptor (FXR) activity. BA sequestration is known to influence BA metabolism and control serum lipid concentrations. Animal data has demonstrated a regulatory role for the FXR in triglyceride metabolism. FXR inhibits hepatic lipogenesis by inhibiting the expression of sterol regulatory element binding protein 1c via small heterodimer primer activity. Conversely, FXR promotes free fatty acids oxidation by inducing the expression of peroxisome proliferator-activated receptor α. FXR can reduce the expression of microsomal triglyceride transfer protein, which regulates the assembly of very low-density lipoproteins (VLDL). FXR activation in turn promotes the clearance of circulating triglycerides by inducing apolipoprotein C-II, very low-density lipoproteins receptor (VLDL-R) and the expression of Syndecan-1 together with the repression of apolipoprotein C-III, which increases lipoprotein lipase activity. There is currently minimal clinical data on triglyceride metabolism in patients with bile acid diarrhoea (BAD). Emerging data suggests that a third of patients with BAD have hypertriglyceridemia. Further research is required to establish the risk of hypertriglyceridaemia in patients with BAD and elicit the mechanisms behind this, allowing for targeted treatment.

BACKGROUND

Glucagon-like peptide-1 (GLP-1) receptor (R) agonists are a class of incretin mimetic drugs that have been used for the treatment of type 2 diabetes mellitus and also considered strong candidates for the treatment of obesity. The original prototypical drug in this class is the exenatide, a synthetic peptide with the same structure as the native molecule, exendin-4, found in the saliva of the Gila monster (Heloderma suspectum suspectum lizard).

OBJECTIVE

To identify and compare the anti-obesogenic, antidyslipidemic and antidiabetogenic effects of agonism in GLP-1R by exenatide on two distinct models of obesity: induced by hypothalamic injury (MSG) or high-calorie diet (DIO).

METHODS

To obtain MSG, neonatal rats were daily subcutaneously injected with 4 g monosodium glutamate/kg, for 10 consecutive days. To obtain DIO, 72-75 days old rats received hyperlipid food and 30% sucrose for drinking up to 142-145 days old. Untreated healthy rats with the same age were used as control. General biometric and metabolic parameters were measured.

RESULTS

MSG was characterized by decreased naso-anal length, food and fluid intake, plasma protein and glucose decay rate per minute after insulin administration (KITT), as well as increased Lee index (body mass0.33/naso-anal length), mass of retroperitoneal and periepididymal fat pads, glycemia, triglycerides (TG), LDL and VLDL. Exenatide ameliorated KITT and food and fluid intake, and it also restored glycemia in MSG. DIO was characterized by glucose intolerance, increased body mass, Lee index, fluid intake, mass of retroperitoneal and periepididymal fat pads, glycemia, glycated hemoglobin (HbA1c), TG, VLDL and total cholesterol, as well as decreased food intake and KITT. Exenatide restored glycemia, HbA1c, TG, VLDL, total cholesterol and body mass, and it also ameliorated food and fluid intake, KITT and mass of retroperitoneal fat pad in DIO.

CONCLUSIONS

The hypothalamic injury and the high-calorie diet induce dyslipidemia and glycemic dysregulation in addition to obesity in rats. The usual therapeutic dose of exenatide in humans is antidiabetogenic in both these obesity models, but is anti-obesogenic and hypolipidemic only in diet-induced obesity. Agonists of GLP-1R are promising anti-obesogenic and antidyslipidemic drugs in the early stages of the obesity, in which the integrity of the nervous system was unaffected.

OBJECTIVE

The aim of this study was to analyze the serum bilirubin level, lipid and lipoprotein parameters with the emphasis on the presence of atherogenic small dense LDL in patients with Gilbert's syndrome and to compare these results with probands in the control group. We used a new electrophoretic method, which enables to analyze up to 12 lipoprotein subpopulations. Atherogenic lipoprotein profile is characterized by the presence of very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL) and the presence of small dense LDL lipoproteins. The presence of LDL1 and LDL2 subpopulations, as well as HDL lipoproteins is considered as protective factor.

METHODS

Molecular - genetic examination of Gilbert\'s syndrome using fragment analysis method was carried out in collaboration with the Centre for Medical Genetics, University Hospital in Bratislava. Total cholesterol and triglycerides in plasma were analyzed from lipid parameters by means of enzymatic CHOD-PAP method, Roche Diagnostics, Germany. Biochemical parameters - bilirubin (total, conjugated and unconjugated), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GMT), (Roche Diagnostics, Germany), TSH, FT3, fT4 (Siemens) were also examined. Serum lipoproteins and their subfractions were examined using Lipoprint LDL System Quantimetrix, CA, USA (12).

RESULTS

We found significantly higher levels of total bilirubin and unconjugated bilirubin in patients with Gilbert's syndrome. In the control group, probands had significantly higher triglycerides levels, VLDL cholesterol levels, IDL cholesterol level, and small dense LDL levels compared to the group with Gilbert\'s syndrome. Probands with Gilbert's syndrome had significantly lower presence of atherogenic lipoprotein spectrum than probands in control group (5% vs. 18%). We found significantly negative correlation between serum unconjugated bilirubin levels and LDL 3-7 (r = - 0.594, p <0.01), as well as between bilirubin and triglycerides (r = -0.540, p<0.01). Serum bilirubin concentration and LDL 1-2 concentration correlated significantly positively (r = 0.451, p <0.05).

CONCLUSIONS

The presence of atherogenic lipoprotein spectrum is determined by the particular representation of small dense LDL. Atherogenic spectrum was presented significantly less in patients with Gilbert\'s syndrome compared with the control group (5% vs. 18%). In our study, we have not followed the risk of coronary heart disease or other manifestations of atherosclerotic arteries disability. However, we found the inverse relationship of serum bilirubin levels and atherogenic small dense LDL. We found out that the protective antiatherogenic effect of hyperbilirubinemia is potentiated by low occurence of strongly atherogenic small dense LDL and persons with byperbilirubionemia (in our case represented Gilbert's syndrome), could be protected against the development of atheroscleosis.

Sarcopenia is an independent predictor of mortality in patients with liver cirrhosis. However, evidence has emerged that skeletal muscles mediate their protective effect against sarcopenia by secreting myokines. Therefore, we investigated whether irisin was associated with sarcopenia in patients with liver cirrhosis. This was an observational cross-sectional study of data collected from 187 cirrhotic patients. Sarcopenia was defined by computed tomography (CT) scans using specific cutoffs of the 3rd lumbar vertebra skeletal muscle index (L₃ SMI). Morning irisin levels were obtained in all patients. Of the 187 patients, sarcopenia was noted in 73 (39%). Irisin concentrations were lower in sarcopenic patients (32.40 pg/ml [interquartile range (IQR): 18.70, 121.26], p < 0.001) than in nonsarcopenic patients. There was a weak correlation between L₃ SMI and irisin levels (r = 0.516, p < 0.001). Multivariable regression analysis including L₃ SMI, body mass index (BMI), very-low-density lipoprotein (VLDL)-cholesterol, aspartate aminotransferase (AST), adiponectin, and irisin levels showed that L₃ SMI (odds ratio [OR] = 0.915, p = 0.023), adiponectin levels (OR = 1.074, p = 0.014), irisin levels (OR = 0.993, p < 0.001) and BMI (OR = 0.456, p = 0.004) were independently associated with sarcopenia. Irisin levels are associated with sarcopenia in patients with liver cirrhosis. This paper addresses a gap in the literature and facilitates the future transition into clinical treatment.