Diabetic dyslipidemia (DD), characterized by increased plasma triglycerides (TGs) and decreased high-density lipoprotein cholesterol (HDL) levels, is a major factor contributing to non-alcoholic steatohepatitis (NASH) and cardiovascular risk in type-2 diabetes. Activation of both the cannabinoid-1 receptor (CB1R) and inducible nitric oxide synthase (iNOS) are associated with NASH progression. Here, we tested whether dual-targeting inhibition of hepatic CB1R and iNOS improves DD in diet-induced obese (DIO) mice. DIO mice were treated for 14 days with (S)-MRI-1867, a peripherally-restricted hybrid inhibitor of CB1R and iNOS. (R)-MRI-1867, the CB1R-inactive stereoisomer which retains iNOS inhibitory activity and JD-5037, a peripherally-restricted CB1R antagonist were used to assess the relative contribution of the two targets to the effects of (S)-MRI-1867. (S)-MRI-1867 reduced hepatic steatosis, the rate of hepatic VLDL secretion, upregulated hepatic LDLR expression and reduced the circulating levels of the proprotein convertase subtilisin/kexin type 9 (PCSK9). The decrease in VLDL secretion could be attributed to CB1R blockade while the reduction of PCSK9 levels and the related increase in LDLR resulted from iNOS inhibition via a mTORC1-dependent mechanism. In conclusion, this approach based on the concomitant inhibition of CB1R and iNOS represents a promising therapeutic strategy for the treatment of dyslipidemia.

<Abst<em>r</em>actText>Nonalcoholic fatty live<em>r</em> disease can lead to hepatic inflammation/damage. Unde<em>r</em>standing the physiological mechanisms that cont<em>r</em>ibute to excess hepatic lipid accumulation may help identify effective t<em>r</em>eatments.</Abst<em>r</em>actText><Abst<em>r</em>actText>We <em>r</em>ec<em>r</em>uited 25 seve<em>r</em>ely obese, non-diabetic patients scheduled fo<em>r</em> ba<em>r</em>iat<em>r</em>ic su<em>r</em>ge<em>r</em>y. To evaluate live<em>r</em> expo<em>r</em>t of t<em>r</em>iglyce<em>r</em>ide-fatty acids, we measu<em>r</em>ed ve<em>r</em>y low density lipop<em>r</em>otein (<em>VLDL</em>)-t<em>r</em>iglyce<em>r</em>ide sec<em>r</em>etion <em>r</em>ates the day p<em>r</em>io<em>r</em> to su<em>r</em>ge<em>r</em>y using an infusion of autologous [1-14C]t<em>r</em>iolein-labeled <em>VLDL</em> pa<em>r</em>ticles. Ketone body <em>r</em>esponse to fasting and int<em>r</em>a-hepatic long chain acylca<em>r</em>nitine concent<em>r</em>ations we<em>r</em>e used as indices of hepatic fatty acid oxidation. We measu<em>r</em>ed int<em>r</em>aope<em>r</em>ative hepatic uptake <em>r</em>ates of plasma f<em>r</em>ee fatty acids using a continuous infusion of [U-13C]palmitate, combined with a bolus dose of [9,10-3H]palmitate and a ca<em>r</em>efully timed live<em>r</em> biopsies. Total int<em>r</em>ahepatic lipids we<em>r</em>e measu<em>r</em>ed in live<em>r</em> biopsy samples to dete<em>r</em>mine fatty live<em>r</em> status. The hepatic concent<em>r</em>ations and en<em>r</em>ichment f<em>r</em>om [U-13C]palmitate in diacylglyce<em>r</em>ols, sphingolipids, and acyl-ca<em>r</em>nitines we<em>r</em>e measu<em>r</em>ed using liquid ch<em>r</em>omatog<em>r</em>aphy/tandem mass spect<em>r</em>omet<em>r</em>y.</Abst<em>r</em>actText><Abst<em>r</em>actText>Amongst study pa<em>r</em>ticipants with fatty live<em>r</em> disease, int<em>r</em>ahepatic lipid was negatively co<em>r</em><em>r</em>elated with <em>VLDL</em>-t<em>r</em>iglyce<em>r</em>ide sec<em>r</em>etion <em>r</em>ates (<em>r</em> = -0.92, P = 0.01), but un<em>r</em>elated to hepatic f<em>r</em>ee fatty acid uptake o<em>r</em> indices of hepatic fatty acid oxidation. <em>VLDL</em>-t<em>r</em>iglyce<em>r</em>ide sec<em>r</em>etion <em>r</em>ates we<em>r</em>e positively co<em>r</em><em>r</em>elated with hepatic concent<em>r</em>ations of satu<em>r</em>ated diacylglyce<em>r</em>ol (<em>r</em> = 0.46, P = 0.02) and sphingosine-1-phosphate (<em>r</em> = 0.44, P = 0.03).</Abst<em>r</em>actText><Abst<em>r</em>actText>We conclude that in non-diabetic, seve<em>r</em>ely obese humans, excess int<em>r</em>ahepatic lipid is associated with limited expo<em>r</em>t of t<em>r</em>iglyce<em>r</em>ide in <em>VLDL</em> pa<em>r</em>ticles <em>r</em>athe<em>r</em> than inc<em>r</em>eased uptake of systemic f<em>r</em>ee fatty acids.</Abst<em>r</em>actText>

Omega-3 long chain polyunsaturated fatty acid (n-3 LCPUFA) supplementation has been shown to improve plasma lipid profiles in men and post-menopausal women, however, data for pre-menopausal women are lacking. The benefits of intakes less than 1 g/day have not been well studied, and dose⁻response data is limited. The aim of this study was to determine the effect of low doses of docosahexaenoic acid (DHA)-rich tuna oil on plasma triglyceride (TG) lowering in pre-menopausal women, and investigate if low dose DHA-rich tuna oil supplementation would increase the low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particle sizes. A randomized, double-blind, placebo-controlled trial was conducted, in which 53 healthy pre-menopausal women with mildly elevated plasma TG levels consumed 0, 0.35, 0.7, or 1 g/day n-3 LCPUFA as HiDHA™ tuna oil or placebo (Sunola oil) capsules for 8 weeks. Supplementation with 1 g/day n-3 LCPUFA, but not lower doses, reduced plasma TG by 23% in pre-menopausal women. This was reflected in a dose-dependent reduction in very-low-density lipoprotein (VLDL)-TG (R² = 0.20, p = 0.003). A weak dose-dependent shift in HDL (but not LDL) particle size was identified (R² = 0.05, p = 0.04). The results of this study indicate that DHA-rich n-3 LCPUFA supplementation at a dose of 1 g/day is an effective TG-lowering agent and increases HDL particle size in pre-menopausal women.

Background: Sampson et al. developed a novel method to estimate very low-density lipoprotein cholesterol (VLDL-C) and low-density lipoprotein cholesterol (LDL-C) in the setting of hypertriglyceridemia. Familial Combined Hyperlipidemia (FCHL) is a common primary dyslipidemia in which lipoprotein composition interferes with LDL-C estimation. This study aimed to evaluate performance of LDL-C using this new method (LDL-S) compared with LDL-C estimated by Friedewald's and Martin eq. (LDL-F, LDL-M) in FCHL.

Methods: Data were collected from 340 subjects with confirmed FCHL. Concordance for VLDL-C measured by ultracentrifugation and LDL-C estimated using these measures compared to Sampson's, Martin's and Friedewald's equations was performed using correlation coefficients, root mean squared error (RMSE) and bias. Also, concordance of misclassified metrics according to LDL-C (< 70 and < 100 mg/dL) and Apo B (< 80 and < 65 mg/dL) thresholds were assessed.

Results: Sampson's equation was more accurate (RMSE 11.21 mg/dL; R² = 0.88) compared to Martin's (RMSE 13.15 mg/dL; R² = 0.875) and the Friedewald's equation (RMSE 13.7 mg/dL; R² = 0.869). When assessing performance according to LDL-C, Sampson's had highest correlation and lowest RMSE compared to other equations (RMSE 19.99 mg/dL; R² = 0.840). Comparing performance strength across triglyceride levels, Sampson's showed consistently improved correlations compared to Martin's and Friedewald's formulas for increasing triglycerides and for the FCHL phenotype of mixed dyslipidemia. Sampson's also had improved concordance with treatment goals.

Conclusions: In FCHL, VLDL-C and LDL-C estimation using Sampson's formula showed higher concordance with lipid targets assessed using VLDL-C obtained by ultracentrifugation compared with Friedewald's and Martin's equations. Implementation of Sampson's formula could improve treatment monitoring in FCHL.

Keywords: Cardiovascular risk; Familial combined hyperlipidemia; Friedewald’s equation; Low-density lipoprotein cholesterol; Martin/Hopkins’ equation; Sampson’ equation; Very low-density lipoprotein cholesterol.

OBJECTIVE

To observe the effect of metformin on the expression of SIRT1 and UCP2 in rat liver of type 2 diabetes mellitus (T2DM) with nonalcoholic fatty liver disease (NAFLD), and discuss the pathogenesis of T2DM with NAFLD, and the treatment with and possible mechanism of metformin.

METHODS

Thirty-six male SD rats were randomly divided into a normal control group (group NC, n=12), a T2DM with NAFLD group (group MC, n=12), and a metformin group (group A, n=12). We established the model of T2DM with NAFLD rats by feeding high-fat and high-sugar diet and injecting STZ. After the success establishment of the model, the metformin group was given metformin 300 mg/(kg.d) for 8 weeks. At the end of the experiment, we measured FBG, ALT, AST, TC, TG, HDL-C, LDL-C, VLDL, FFAs, FINs and HOMA-IR respectively in group NC, MC and A. We observed the change of liver tissue pathology by HE, determined the expression of SIRT1 and UCP2 in rat liver by immunohistochemical method and real-time quantitative method.

RESULTS

FBG, ALT, AST, TC, TG, LDL-C, VLDL, FFAs, FINs and HOMA-IR were higher in group MC than in group NC (P<0.05), while HDL-C was obviously lower in group MC than in group NC (P<0.05). After the metformin treatment, the serum parameters in the rats had improved in group NC compared with in group MC (P<0.05). On immunohistochemical staining and mRNA level, the expression of SIRT1 was obviously lower in group MC than in group NC (P<0.05), and the expression of UCP2 was obviously higher in group MC than in group NC (P<0.05). After the metformin treatment, the expression of SIRT1 was higher than in group MC (P<0.05), and the expression of UCP2 was lower than in group MC (P<0.05). There was negative correlation between the expression of SIRT1 and UCP2 (r=-0.61, P<0.01).

CONCLUSIONS

The expression of SIRT1 is low and the expression of UCP2 is high in rat liver of T2DM with NAFLD. Metformin can increase the expression of SIRT1 and reduce the expression of UCP2, with negative correlation between the expression of SIRT1 and UCP2.

The prevalence of non-alcoholic fatty liver disease (NAFLD), which is developed from hepatic steatosis, is increasing worldwide. However, no specific drugs for NAFLD have been approved yet. To observe the effects of Rho, a fraction from Rhodiola crenulate, on non-alcoholic hepatic steatosis, three mouse models with characteristics of NAFLD were used including high-fat diet (HFD)-induced obesity (DIO) mice, KKAy mice, and HFD combined with tetracycline stimulated Model-T mice. Hepatic lipid accumulation was determined via histopathological analysis and/or hepatic TG determination. The responses to insulin were evaluated by insulin tolerance test (ITT), glucose tolerance test (GTT), and hyperinsulinemic-euglycemic clamp, respectively. The pathways involved in hepatic lipid metabolism were observed via western-blot. Furthermore, the liver microcirculation was observed by inverted microscopy. The HPLC analysis indicated that the main components of Rho were flavan polymers. The results of histopathological analysis showed that Rho could ameliorate hepatic steatosis in DIO, KKAy, and Model-T hepatic steatosis mouse models, respectively. After Rho treatment in DIO mice, insulin resistance was improved with increasing glucose infusion rate (GIR) in hyperinsulinemic-euglycemic clamp, and decreasing areas under the blood glucose-time curve (AUC) in both ITT and GTT; the pathways involved in fatty acid uptake and de novo lipogenesis were both down-regulated, respectively. However, the pathways involved in beta-oxidation and VLDL-export on hepatic steatosis were not changed significantly. The liver microcirculation disturbances were also improved by Rho in DIO mice. These results suggest that Rho is a lead nature product for hepatic steatosis treatment. The mechanism is related to enhancing insulin sensitivity, suppressing fatty acid uptake and inhibiting de novo lipogenesis in liver.

OBJECTIVE

This was to determine the serum lipid profile of preeclamptic women and their association with severity of preeclampsia.

METHODS

This was a case control study conducted at the Lagos University Teaching Hospital, Lagos, Nigeria. Blood samples for serum lipid estimation were collected after an overnight fast. The National Cholesterol Education Program - Adult Treatment Panel (ATP) III criteria were used to define dyslipidemia.

RESULTS

Two hundred forty women participated in the study. The mean total cholesterol of preeclamptic and normotensive women was 309.9 ± 10.4 mg/dl and 237 ± 6.8 mg/dl, respectively. Both groups of women had higher than normal mean levels of triglycerides (TG) (203.3 ± 11.0 mg/dl versus 157.5 ± 7.1 mg/dl); low-density lipoprotein (LDL)-c (156.5 ± 11.0 mg/dl versus 109.7 ± 6.9 mg/dl); high-density lipoprotein (HDL)-c (63.2 ± 2.5 mg/dl versus 55.4 ± 1.8 mg/dl) and very low-density lipoprotein (VLDL) (39.5 ± 2.0 mg/dl versus 31.5 ± 1.4 mg/dl). Fewer women with preeclampsia had isolated hypertriglyceridemia (95 versus 99%). Maternal serum total cholesterol (TC), TG, and LDL was significantly (p < .001) higher in severe, compared to mild preeclampsia. Pearson's correlation indicated that all lipids, including total cholesterol (r = 0.406) had positive correlation with preeclampsia.

CONCLUSIONS

There is elevated serum lipid in pregnancy irrespective of preeclampsia developing. The positive correlation of maternal serum lipids to preeclampsia suggests a casual relationship.

Weight loss induced by decreased energy intake (diet) or exercise generally has favorable effects on insulin sensitivity and cardiometabolic risk. The variation in these responses to diet-induced weight loss with or without exercise, particularly in older obese adults, is less clear. The objectives of our study were to (1) examine the effect of weight loss with or without exercise on the variability of responses in insulin sensitivity and cardiometabolic risk factors and (2) to explore whether baseline phenotypic characteristics are associated with response. Sedentary older obese (BMI 36.3 ± 5.0 kg/m²) adults (68.6 ± 4.7 years) were randomized to one of 3 groups: health education control (HED); diet-induced weight loss (WL); or weight loss and exercise (WL + EX) for 6 months. Composite Z-scores were calculated for changes in insulin sensitivity (C_IS: rate of glucose disposal/insulin at steady state during hyperinsulinemic euglycemic clamp, HOMA-IR, and HbA1C) and cardiometabolic risk (C_CMR: waist circumference, triglycerides, and fasting glucose). Baseline measures included body composition (MRI), cardiorespiratory fitness, in vivo mitochondrial function (ATPmax; P-MRS), and muscle fiber type. WL + EX groups had a greater proportion of High Responders in both C_IS and C_CMR compared to HED and WL only (all p < 0.05). Pre-intervention measures of insulin (r = 0.60) and HOMA-IR (r = 0.56) were associated with change in insulin sensitivity (C_IS) in the WL group (p < 0.05). Pre-intervention measures of glucose (r = 0.55), triglycerides (r = 0.53), and VLDL (r = 0.53) were associated with change in cardiometabolic risk (C_CMR) in the WL group (p < 0.05), whereas triglycerides (r = 0.59) and VLDL (r = 0.59) were associated with C_CMR (all p < 0.05) in WL + EX. Thus, the addition of exercise to diet-induced weight loss increases the proportion of older obese adults who improve insulin sensitivity and cardiometabolic risk. Additionally, individuals with poorer metabolic status are more likely to experience greater improvements in cardiometabolic risk during weight loss with or without exercise.

<st<em>r</em>ong class="sub-title"> Keywo<em>r</em>ds: </st<em>r</em>ong> ca<em>r</em>diometabolic <em>r</em>isk; exe<em>r</em>cise; individual va<em>r</em>iability; insulin sensitivity; olde<em>r</em> adults; <em>r</em>esponse; weight loss.

BACKGROUND

Little is known so far on the lipid profile in polymyositis (PM) patients. Our aim is to identify lipid profiles in untreated patients with early PM, to assess the association between lipid profiles and C-reactive protein (a sensitive marker of inflammation) in these patients.

RESULTS

This work was conducted as a case-control study. Sixty untreated patients with PM and 60 age- and sex-matched healthy controls were included. The duration of PM was less than six months, and none of them had received intermittent or regular corticosteroids or disease-modifying antirheumatic drugs or biological agents prior to the study. Triglyceride (TG), total cholesterol (TC), LDL-cholesterol (LDL-C), and HDL-cholesterol (HDL-C), and C-reactive protein (CRP) were assessed using standard techniques. Thirty patients (50%) had a decreased level of HDL-C and 47% had an increased level of TG. The levels of HDL-C, LDL-C, and TC in PM were significantly lower than in controls (P<0.001, P<0.01, P<0.001, respectively). The level of TG was significantly higher in PM than in controls (P<0.001). The level of very low LDL-cholesterol (VLDL-C), and the ratios of VLDL-C/LDL-C, TC/HDL-C, and LDL-C/HDL-C were significantly higher than in controls (all P<0.001). Serum CRP levels correlated negatively with HDL-C (r = -0.352, P = 0.006) and TC (r = -0.262, P = 0.043). After adjustment for age, gender, smoking, drinking, body mass index, and pulmonary fibrosis/infection, linear regression model demonstrated that CRP is associated with HDL-C among PM patients (P = 0.028).

CONCLUSIONS

Dyslipidemia is a common feature in patients with PM that is characterized by a decrease in HDL-C and an increase in TG, suggesting a high risk of atherosclerosis. The Inflammatory condition in PM may account for the metabolism of HDL-C.

<st<em>r</em>ong class="sub-title"> Backg<em>r</em>ound: </st<em>r</em>ong> The de<em>r</em>angement of se<em>r</em>um lipids is well documented in psychiat<em>r</em>ic diso<em>r</em>de<em>r</em>s like schizoph<em>r</em>enia, mania, and dep<em>r</em>ession but not in obsessive compulsive diso<em>r</em>de<em>r</em> (OCD), whe<em>r</em>e it has been inadequately examined. Also, se<em>r</em>um lipid abno<em>r</em>malities a<em>r</em>e inc<em>r</em>easingly found in "impulsivity," an impo<em>r</em>tant sub-const<em>r</em>uct of OCD. Ou<em>r</em> study aimed to examine se<em>r</em>um lipid p<em>r</em>ofile among patients with OCD and its association with clinical p<em>r</em>ofile and impulsivity among them.

<st<em>r</em>ong class="sub-title"> Methods: </st<em>r</em>ong> Fo<em>r</em>ty d<em>r</em>ug naïve o<em>r</em> d<em>r</em>ug-f<em>r</em>ee (fou<em>r</em> weeks fo<em>r</em> o<em>r</em>al and eight weeks fo<em>r</em> any depot psychot<em>r</em>opics) patients with OCD acco<em>r</em>ding to Inte<em>r</em>national Classification of Disease -10^th ve<em>r</em>sion (ICD-10): Diagnostic C<em>r</em>ite<em>r</em>ia fo<em>r</em> Resea<em>r</em>ch (DCR) by the Wo<em>r</em>ld Health O<em>r</em>ganization (WHO), f<em>r</em>om outpatient and inpatient depa<em>r</em>tments of a te<em>r</em>tia<em>r</em>y ca<em>r</em>e psychiat<em>r</em>ic hospital we<em>r</em>e <em>r</em>ec<em>r</em>uited. Measu<em>r</em>es like Yale-B<em>r</em>own Obsessive Compulsive Scale (Y-BOCS), Hamliton Rating Scale fo<em>r</em> Dep<em>r</em>ession (HAM-D), Ba<em>r</em><em>r</em>att's Impulsivity Scale (BIS-11), and Hamilton Rating Scale fo<em>r</em> Anxiety (HAM-A) we<em>r</em>e administe<em>r</em>ed. Fo<em>r</em>ty age and sex-matched healthy cont<em>r</em>ols (HC) we<em>r</em>e <em>r</em>ec<em>r</em>uited afte<em>r</em> sc<em>r</em>eening with Gene<em>r</em>al Health Questionnai<em>r</em>e 12 (GHQ-12). Se<em>r</em>um lipids we<em>r</em>e assessed in both the g<em>r</em>oups.

<st<em>r</em>ong class="sub-title"> Results: </st<em>r</em>ong> Se<em>r</em>um high density lipop<em>r</em>oteins (HDL) (<i>P</i> < 0.001; pa<em>r</em>tial η² = 0.176) and apolipop<em>r</em>otein B (<i>P</i> < 0.001; pa<em>r</em>tial η² = 0.531) we<em>r</em>e significantly highe<em>r</em> in OCD g<em>r</em>oup than age- and sex-matched HC. A t<em>r</em>end towa<em>r</em>d lowe<em>r</em> se<em>r</em>um HDL (<i>P</i> = 0.06; pa<em>r</em>tial η² = 0.060) was obse<em>r</em>ved among patients of OCD with high impulsivity. Se<em>r</em>um HDL was negatively co<em>r</em><em>r</em>elated with BIS attention (<em>r</em>_s =-0.32; <i>p</i> = 0.03), BIS moto<em>r</em> (<em>r</em>_s = 0.40; <i>P</i> = 0.01), BIS non-planning (<em>r</em>_s = - 0.36; <i>P</i> = 0.02), and BIS total (<em>r</em>_s = - 0.36; <i>P</i> = 0.01) sco<em>r</em>es. Se<em>r</em>um t<em>r</em>iglyce<em>r</em>ides (TG) (<em>r</em>_s = 0.34; <i>P</i> = 0.03) and apolipop<em>r</em>otein B (<em>r</em>_s = -0.32; <i>P</i> = 0.04) we<em>r</em>e negatively co<em>r</em><em>r</em>elated with Y-BOCS compulsion sco<em>r</em>e. Se<em>r</em>um TG (<em>r</em>_s = -0.45, <i>P</i> < 0.01) and se<em>r</em>um ve<em>r</em>y low density lipop<em>r</em>otein (<em>VLDL</em>) was negatively (<em>r</em>_s = -0.39; <i>P</i> = 0.01) co<em>r</em><em>r</em>elated with Y-BOCS total sco<em>r</em>es. Se<em>r</em>um <em>VLDL</em> was positively (<em>r</em>_s = 0.34; <i>P</i> = 0.03) co<em>r</em><em>r</em>elated with BIS moto<em>r</em> sco<em>r</em>es.

<st<em>r</em>ong class="sub-title"> Conclusions: </st<em>r</em>ong> Se<em>r</em>um lipid f<em>r</em>actions a<em>r</em>e de<em>r</em>anged among patients with OCD. Diffe<em>r</em>ent lipid f<em>r</em>actions have diffe<em>r</em>ent associations with clinical p<em>r</em>ofiles of OCD. Impulsivity among patients with OCD may have a specific association with se<em>r</em>um lipids. A small sample size, use of self-<em>r</em>epo<em>r</em>t measu<em>r</em>e without adaptation fo<em>r</em> impulsivity, a lack of metabolic p<em>r</em>ofile assessment among pa<em>r</em>ticipants, and a lack of assessment of impulsivity among HC we<em>r</em>e the limitations of ou<em>r</em> tudy.

<st<em>r</em>ong class="sub-title"> Keywo<em>r</em>ds: </st<em>r</em>ong> Impulsivity; OCD; Se<em>r</em>um lipids a<em>r</em>e de<em>r</em>anged in OCD. Se<em>r</em>um lipids a<em>r</em>e also va<em>r</em>yingly co<em>r</em><em>r</em>elated with impulsivity and seve<em>r</em>ity of OCD.; lipids; obsessive-compulsive diso<em>r</em>de<em>r</em>.

Experiments were carried out in order to evaluate the effect of various levels of dietary zinc supplementation on the zinc status, growth and contents of retinol-binding protein (RBP), tocopherol and lower density lipoproteins (VLDL + LDL) in serum of rats fed on diets containing rapeseed protein concentrate (RPC) or casein as the sole source of protein. In male rats fed on RPC diet at a 10% protein 5% fat level, a highly significant correlation was found between dietary zinc content and the total tibia zinc content (r = 0.946) in the dietary zinc range of 35-137 microgram/mg. In contrast, the casein rats attained almost maximal bone zinc contents even at the lower level of dietary zinc. No correlation was found between zinc status and the protein efficiency ratio obtained for the rapeseed protein. In female rats fed on a zinc-supplemented RPC diet at a 20% protein and 10% fat level, the serum levels of tocopherol and VLDL + LDL were reduced in comparison to the levels observed in female rats fed on a corresponding casein diet. No diet-related changes in serum levels of RBP were found. However, male rats showed significantly higher RBP values than the female rats.

The aim of this study was to investigate the effects of trans-fatty acids (TFA) on liver and serum TAG regulation in mice fed diets containing different proportions of n-3, n-6 and n-9 unsaturated fatty acids (UFA) from olive (O), maize (C) or rapeseed (R) oils partially substituted or not with TFA (Ot, Ct and Rt, respectively). Male CF1 mice were fed (30 d) one of these diets. The effects of the partial substitution (1 %, w/w) of different UFA with TFA on the activity and expression of hepatic enzymes involved in lipogenesis and fatty acids oxidation were evaluated, as well as their transcription factor expressions. Some of the mechanisms involved in the serum TAG regulation, hepatic VLDL rich in TAG (VLDL-TAG) secretion rate and lipoprotein lipase (LPL) activity were assessed. In liver, TFA induced an increase in TAG content in the Ot and Rt groups, and this effect was associated with an imbalance between lipogenesis and β-oxidation. In the Ot group, exacerbated lipogenesis may be one of the mechanisms responsible for the liver steatosis induced by TFA, whereas in Rt it has been related to a decreased β-oxidation, compared with their respective controls. The enhanced hepatic VLDL-TAG secretion in the Ot and Rt groups was compensated with a differential removal of TAG by LPL enzyme in extrahepatic tissues, leading to unchanged serum TAG levels. In brief, the effects of low levels of TFA on liver and serum TAG regulation in mice depend on the dietary proportions of n-3, n-6 and n-9 UFA.

It is now known that possession of one of the three common forms of the apolipoprotein E gene (allele epsilon 4) confers an increased risk for Alzheimer's disease (AD), both familial and sporadic, and that this risk is dose-dependent. Other genes that may play a role in AD, either through independent association with the disease or through modification of, or interaction with, the existing apolipoprotein E (APOE) risk, are now under investigation including the alpha-1-antichymotrypsin (ACT) gene, the very low density lipoprotein receptor (VLDL-R) gene, and the presenilin-1 (PS-1) gene. Kamboh et al. [1995] reported that a polymorphism in the alpha-1-antichymotrypsin gene could modify the risk for AD conferred by the APOE locus, specifically by increasing the risk for AD among epsilon 4 homozygotes. The ACT gene, which is found on chromosome 14, has previously been proposed as a candidate for AD due to the presence of the ACT protein in senile plaques and the reported elevation of the protein in the cerebro-spinal fluid (CSF) and serum of AD cases. We have investigated this reported association within our familial and sporadic AD dataset, where we find no independent association between ACT and the occurrence of AD. Logistic regression analysis excludes ACT or the interaction between ACT and APOE as significant contributors in the prediction of disease status. By this analysis, ACT genotyping does not provide additional information about an individual's risk of Alzheimer's disease beyond the risk information conferred by APOE genotype alone.

The accumulation of the oxidized apolipoprotein, apoB-100, containing lipoproteins in the arterial wall and the progression of coronary atherosclerotic lesions in rabbits with beta-VLDL and LDL hypercholesterolemia was compared. In New Zealand White (NZW) rabbits on a 0.125% cholesterol diet, LDL cholesterol levels increased from 14 +/- 1 mg/dL (mean +/- SEM; n = 9) to 170 +/- 34 mg/dL (n = 10, P = .0002). On 0.5% cholesterol, LDL cholesterol levels were similar, but beta-VLDL cholesterol levels increased from 60 +/- 4 mg/dL (n = 10) to 550 +/- 75 mg/dL (n = 8; P < .0001). In Watanabe heritable hyperlipidemic (WHHL) rabbits, LDL cholesterol levels were 2.3-fold higher (n = 13; P < .0001) than in NZW rabbits on 0.5% cholesterol, whereas their beta-VLDL cholesterol levels were 3.7-fold lower (P < .0001), resulting in similar total cholesterol levels. At 2 months, mean intimal areas of lesions in the coronary arteries of NZW rabbits on 0.125% cholesterol were 0.13 +/- 0.045 mm2 (n = 4; mean +/- SEM) and were 5.8-fold, (n = 4; P = .016) and 2.0-fold (n = 6; P = NS versus 0.125% cholesterol and P = .014 versus 0.5% cholesterol) higher in NZW rabbits on 0.5% cholesterol and in WHHL rabbits, respectively. At 5 months, mean intimal areas were 0.47 +/- 0.088 mm2 (n = 6) in NZW rabbits on 0.125% cholesterol and were 4.5-fold (n = 4; P = .0001) and 2.0-fold (n = 7; P = .012 and P = .0019) higher in rabbits on 0.5% cholesterol and in WHHL rabbits, respectively. Levels of oxidized apoB-100 containing lipoproteins (both beta-VLDL and LDL) in the lesions correlated with mean intimal area (r = .88; n = 31; P < .0001) of those lesions and with the plasma levels of total beta-VLDL/LDL (r = .72; P < .0001). Levels of oxidized apoB-100 containing lipoproteins in the arterial wall correlate with progression of hypercholesterolemia-induced coronary atherosclerotic lesions. Plasma levels of beta-VLDL relative to similar increases in LDL result in a more pronounced accumulation of oxidized apoB-100 containing lipoproteins in the arterial wall and in the plasma and a more rapid progression of coronary atherosclerosis.

The effect of normo (NTG)- and hypertriglyceridemic (HTG)-VLDL on cultured human umbilical vein endothelial cell (HUVEC) surface-localized fibrinolysis was examined following pre-incubation with NTG-, HTG-VLDL, LDL (1-20 micrograms/mL) or buffer (control). Ligand binding assays, using 125I-labeled tcu-PA, t-PA, or Glu-plasminogen (Glu-Pmg) were carried out in the absence/presence of lipoproteins. Scatchard analyses showed that HTG-VLDL decreased the Bmax for 125I-labeled Glu-Pmg ligand binding approximately 35% [(2.11 +/- 0.39)-(1.40 +/- 0.32) x 10(6) sites/cell, p < 0.005] and increased the Kd, app approximately 5-fold (0.32 +/- 0.03 to 1.74 +/- 0.08 microM, p < 0.01), while NTG-VLDL, LDL, and buffer had no effect. 125I-labeled PA ligand binding was unaffected by these lipoproteins. Receptor-bound PA activation of cell-bound 125I-labeled Glu-Pmg was measured by quantitation of either the M(r) 20 kDa light- or M(r) 60 kDa heavy-chain of 125I-labeled plasmin, following SDS-PAGE. Kinetic analysis of these data (HTG-VLDL vs controls) indicated that HTG-VLDL decreased the V(max) of tcu-PA- and t-PA-mediated activation of plasminogen approximately 2.7-fold (0.317 +/- 0.023 vs 0.869 +/- 0.068 nM s-1, p < 0.01) and approximately 2.9-fold (0.391 +/- 0.098 vs 1.152 +/- 0.265 nM s-1, p < 0.01), respectively. Increasing concentrations of the HTG-VLDL increased 1/V(max), yielding a series of parallel plots, typical for uncompetitive inhibition with a Ki for inhibition of approximately 10 micrograms/mL. The combined ligand binding and kinetic data best fit an uncompetitive inhibition model in which the binding of the large HTG-VLDL particle to the EC surface may directly affect Glu-Pmg binding and activation, thus contributing to early fibrin deposition and the increased thrombotic risk associated with HTG.

The livers of both baboons and rhesus monkeys fed a high fat, high cholesterol diet secreted very low density lipoproteins (VLDL) that were enriched in cholesteryl ester and apoe as compared to VLDL secreted by the livers of chow-fed animals. Stimulation of macrophage cholesterol esterification by the experimental VLDL was compared to that produced by the standard beta-VLDL obtained from the plasma of a rhesus monkey fed 25% coconut oil plus 2% cholesterol. This standard beta-VLDL stimulated 7- to 10-fold more esterification than did the bovine albumin control. Hepatic VLDL from fat-fed animals stimulated esterification in J774 macrophages 50 to 150% as well as did the standard beta-VLDL, even though hepatic VLDL did not display beta electrophoretic mobility on agarose gel electrophoresis. Plasma VLDL from lard-fed baboons did not exhibit beta electrophoretic mobility but did stimulate esterification in macrophages. Baboons were divided into high and low responders based on the change in plasma cholesterol levels in response to a high fat, high cholesterol diet. Both plasma and hepatic VLDL from high responders stimulated cholesterol esterification, whereas hepatic VLDL obtained from low responders or chow-fed baboons did not stimulate cholesterol esterification in macrophages. There was a strong positive correlation (r = 0.866) between the number of apoE molecules per VLDL particle in VLDL obtained from chow-fed, lard-fed, or coconut oil-fed primates and the rate of cholesterol esterification in macrophages. Our results show that hepatic perfusate VLDL obtained from fat- and cholesterol-fed primates have compositional and functional properties usually ascribed to circulating beta-VLDL, without displaying beta mobility, and indicate that the liver may be an important source of atherogenic lipoproteins.

BACKGROUND

No study has been undertaken among rural adult population of India to investigate the association of cardiometabolic risk factors with TV watching.

METHODS

This cross-sectional study was carried out in 1007 participants (645 males and 362 females) aged 20-80 years from a rural community. Anthropometric measures were collected using standard techniques. HOMA-IR was calculated accordingly.

RESULTS

The significant higher value for MWC, WHtR, TER, SF4, BMI, %BF, FM, VFL, IVF, TC, LDL and FBG was observed with increasing duration of TV watching. No significant change was observed for TG, HDL, VLDL, DBP and MAP. Chi-square revealed significant difference for central obesity between male and females across TV watching category. The higher metabolic syndrome phenotypes were prevalent among both sexes with increasing duration of TV watching. Furthermore, multiple regression analyses (stepwise) revealed that occupation, monthly income, duration of TV watching in a day, education and monthly expenditure cumulatively explained ∼19% (R(2)=0.191) of the total variance of % body fat in the study.

CONCLUSIONS

It seems rational to argue that lengthy TV watching time might have detrimental effect on CVD health.

The degree of apo E sialylation in VLDL from serum of diabetics and controls was determined by densitometric scanning of the pherograms after isoelectric focusing of the VLDL proteins including treatment with neuraminidase. The distribution pattern of sialylation within the groups of patients and controls followed a Gaussian type. A significantly elevated level of sialylated apo E could be demonstrated in IDDM and NIDDM as compared to the controls. No correlation was found between the apo E phenotype and the diabetic state. From the correlation analysis including the parameters degree of sialylation, age, duration of diabetic state, and blood glucose pattern no significant results were obtained except a significant but only week correlation (r less than 0.3) between sialylation, age, and blood glucose in IDDM patients. Possible consequences of the elevated apo E sialylation in diabetes mellitus are discussed.

Type 2 diabetes (T2D) is a complex disease with an elusive link between its molecular aetiology and clinical presentation. Although, the role of visceral adipose tissue in insulin-resistance and T2D is known, limited information is available on the role of peripheral-subcutaneous adipose tissue especially in Asian Indians. In this microarray-based study of diabetic and normal glucose tolerant Asian Indians, we generated the transcriptome of their thigh adipose tissue and analyzed differentially expressed genes (DEGs) using weighted gene co-expression network analysis; further we identified perturbed pathways implicated by these DEGs in relevant co-expression modules. We also attempted to link these pathways with known aspects of T2D pathophysiology in terms of their association with some of their intermediate traits, namely; adipocyte size, HOMA-B, HOMA-R, Hb1Ac, insulin, glucose-level, TNF-α, IL-6, VLDLs, LDLs, HDLs, and NEFAs. It was observed that several modules of co-expressed genes show an association with diabetes and some of its intermediate phenotypic traits mentioned above. Therefore, these findings suggest a role of peripheral subcutaneous adipose tissue in the pathophsiology of T2D in Asian Indians. Additionally, our study indicated that the peripheral subcutaneous adipose tissue in diabetics shows pathologic changes characterized by adipocyte hypertrophy and up-regulation of inflammation-related pathways.

The whole lipoprotein spectrum of human plasma may be divided into atherosclerotic and anti-atherosclerotic lipoproteins. To the first class belong apolipoprotein (apo) B and some apoE-containing lipoproteins of the very-low-density (VLDL), intermediate-density (IDL) and low-density (LDL) lipoprotein fractions. Anti-atherosclerotic lipoproteins are apoA-containing high-density lipoproteins (HDL). Circulating plasma lipoproteins are catabolized mainly by specific cell surface receptors (R) which react with apoB and apoE (B/E-R), for apoE (E-R) or for apoA (HDL-R). Whereas the B/E-R and E-R are responsible for the cellular uptake of lipoproteins and their lipid load by various organs, HDL-R are thought to promote lipid (cholesterol) efflux. There is an additional class of lipoprotein receptors, the so called scavenger-R which are responsible for the removal of altered or degraded lipoproteins for the circulation. Under normal physiological conditions, the concerted action of these receptors warrants efficient lipoprotein turnover and direction into target organs. Derangements of this system, however, may lead to the deposition and accumulation of atherogenic lipids, notably free cholesterol (FC) and cholesteryl esters (CE) in arterial tissue causing atherosclerosis and cardiac death.

Apolipoprotein B-100 (apo B) is the principal structural and functional protein of the pro-atherogenic lipoproteins, but its homeostasis in man has not been clearly established. The hepatic availability of cholesterol substrate may be a determining factor. We examined whether there was a direct correlation between plasma concentrations of mevalonic acid (MVA) and lathosterol (indices of in vivo cholesterol synthesis) and hepatic secretion of very-low-density lipoprotein (VLDL) apo B in 13 normolipidaemic, healthy male subjects. The secretion of VLDL apo B was measured using a primed constant intravenous infusion of 1-[13C]-leucine (1 mg/kg per h) over 8 h. Gas-chromatography mass spectrometry (GCMS) was used to derive isotopic enrichment of apo B and fractional turnover rate was calculated using a monoexponential function. There was a highly significant positive correlation between the absolute secretion rate (ASR) of VLDL apo B and the plasma concentrations of mevalonic acid (r = 0.72, P = 0.005) and lathosterol (r = 0.81, P = 0.001) and the lathosterol:cholesterol ratio (r = 0.79, P = 0.001). In multiple regression analysis, these correlations remained significant after adjusting for waist circumference, age, apolipoprotein E genotype and dietary fat intake. The data further support the notion that the availability of cholesterol substrate regulates the hepatic secretion rate of apo B.

Lipoprotein compositional studies were carried out in 20 patients with atherosclerotic peripheral vascular disease. Twelve of these patients were normolipidemic, the other eight, hypertriglyceridemic. Ten normolipidemic and 10 hypertriglyceridemic age-matched subjects were used as controls. High density lipoprotein cholesterol levels were markedly reduced in the hypertriglyceridemic subjects, both with (35.1 +/- 5.0 mg/dl) and without (36.2 +/- 11.7 mg/dl) peripheral vascular disease, as compared to the normolipidemic patients (47.0 +/- 6.3 mg/dl) and controls (48.1 +/- 10.0 mg/dl). A decreased relative content of apo C-11 in very low density lipoproteins in the hypertriglyceridemic subjects, as compared to the normolipidemics, was detected by isoelectric focusing. Hypertriglyceridemia in patients with peripheral vascular disease shows a typical Type IV lipoprotein and apoprotein profile. Apoprotein B levels in very and low density lipoproteins were determined by electroimmunodiffusion and selective precipitation with tetramethylurea (r = 0.981 between the two methods). All the patients with peripheral vascular disease showed an increased apo B content in very low density lipoproteins vascular disease showed an increased apo B content in very low density lipoproteins (VLDL) as compared to controls (apo B cholesterol in VLDL = 0.341 +/- 0.124 for peripheral vascular disease patients and 0.236 +/- 0.086 for controls, p less than 0.001). A significant correlation between VLDL cholesterol and apo b levels was detected both in peripheral vascular disease patients and in controls; however, two distinct populations could be clearly separated (slopes of the regression lines: peripheral vascular disease patients = 0.350; controls = 0.215, p less than 0.001). The data suggest a possible discriminatory power of VLDL-apo B levels in patients with peripheral vascular disease independent from other lipoprotein and lipid parameters.