HDL Protein Research Articles

Impaired high-density lipoprotein function in patients with heart failure

Abstract Background We recently showed that a lower high-density lipoprotein cholesterol (HDL-C) concentration was one of the strongest predictors of death or heart failure (HF) hospitalisation in patients with HF. In a follow-up study, we suggested that this association could be partly explained by HDL proteome composition. However, whether the emerging concept of HDL function contributes to prognosis of HF patients has not been addressed. Methods We measured three key HDL function metrics, namely cholesterol efflux, antioxidative capacity, and anti-inflammatory capacity, at baseline and after 9 months in 446 randomly selected HF patients from BIOSTAT-CHF. Additionally, the relationship between HDL functionality and HDL proteome composition was determined in 86 patients. Results From baseline to 9 months, HDL-C concentrations did not substantially change, but HDL-mediated cholesterol efflux and anti-inflammatory capacity had decreased (both P<0.001). In contrast, antioxidative capacity improved during the 9 months follow-up (P<0.001). Higher HDL-mediated cholesterol efflux was independently associated with lower risk of mortality after adjustment for BIOSTAT risk models and log HDL-C (HR=0.81 [95% CI: 0.71–0.92], P=0.001). Other functionality parameters were not associated with outcome. Several HDL proteins correlated with HDL functionality, mainly with cholesterol efflux, and apolipoprotein A1 emerged as the main protein associated with all three functionality parameters. Conclusions HDL-mediated cholesterol efflux and anti-inflammatory capacity significantly decreased over time in patients with HF. Better baseline cholesterol efflux was prospectively associated with reduced mortality during follow-up independent of HDL-C. Combined these data indicate that HDL function measurements have the potential to provide clinical information beyond static HDL-C concentrations in HF patients. Changes in HDL functionality over time Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): European Commission

High-Density Lipoprotein Carries Markers That Track With Recovery From Stroke

Prospective cohort studies question the value of HDL-C (high-density lipoprotein cholesterol) for stroke risk prediction. Investigate the relationship between long-term functional recovery and HDL proteome and function. Changes in HDL protein composition and function (cholesterol efflux capacity) in patients after acute ischemic stroke at 2 time points (24 hours, 35 patients; 96 hours, 20 patients) and in 35 control subjects were measured. The recovery from stroke was assessed by 3 months, the National Institutes of Health Stroke Scale and modified Rankin scale scores. When compared with control subject after adjustments for sex and HDL-C levels, 12 proteins some of which participate in acute phase response and platelet activation (APMAP [adipocyte plasma membrane-associated protein], GPLD1 [phosphate inositol-glycan specific phospholipase D], APOE [apolipoprotein E], IHH [Indian hedgehog protein], ITIH4 [inter-alpha-trypsin inhibitor chain H4], SAA2 [serum amyloid A2], APOA4 [apolipoprotein A-IV], CLU [clusterin], ANTRX2 [anthrax toxin receptor 2], PON1 [serum paraoxonase/arylesterase], SERPINA1 [alpha-1-antitrypsin], and APOF [apolipoprotein F]) were significantly (adjusted P<0.05) altered in stroke HDL at 96 hours. The first 8 of these proteins were also significantly altered at 24 hours. Consistent with inflammatory remodeling, cholesterol efflux capacity was reduced by 32% (P<0.001) at both time points. Baseline stroke severity adjusted regression model showed that changes within 96-hour poststroke in APOF, APOL1, APMAP, APOC4 (apolipoprotein C4), APOM (apolipoprotein M), PCYOX1 (prenylcysteine oxidase 1), PON1, and APOE correlate with stroke recovery scores (R2=0.38-0.73, adjusted P<0.05). APOF (R2=0.73) and APOL1 (R2=0.60) continued to significantly correlate with recovery scores after accounting for tPA (tissue-type plasminogen activator) treatment. Changes in HDL proteins during early acute phase of stroke associate with recovery. Monitoring HDL proteins may provide clinical biomarkers that inform on stroke recuperation.

Effect of niacin monotherapy on high density lipoprotein composition and function

BackgroundNiacin has modest but overall favorable effects on plasma lipids by increasing high density lipoprotein cholesterol (HDL-C) and lowering triglycerides. Clinical trials, however, evaluating niacin therapy for prevention of cardiovascular outcomes have returned mixed results. Recent evidence suggests that the HDL proteome may be a better indicator of HDL’s cardioprotective function than HDL-C. The objective of this study was to evaluate the effect of niacin monotherapy on HDL protein composition and function.MethodsA 20-week investigational study was performed with 11 participants receiving extended-release niacin (target dose = 2 g/day) for 16-weeks followed by a 4-week washout period. HDL was isolated from participants at weeks: 0, 16, and 20. The HDL proteome was analyzed at each time point by mass spectrometry and relative protein quantification was performed by label-free precursor ion intensity measurement.ResultsIn this cohort, niacin therapy had typical effects on routine clinical lipids (HDL-C + 16%, q < 0.01; LDL-C − 20%, q < 0.01; and triglyceride − 15%, q = 0.1). HDL proteomics revealed significant effects of niacin on 5 proteins: serum amyloid A (SAA), angiotensinogen (AGT), apolipoprotein A-II (APOA2), clusterin (CLUS), and apolipoprotein L1 (APOL1). SAA was the most prominently affected protein, increasing 3-fold in response to niacin (q = 0.008). Cholesterol efflux capacity was not significantly affected by niacin compared to baseline, however, stopping niacin resulted in a 9% increase in efflux (q < 0.05). Niacin did not impact HDL’s ability to influence endothelial function.ConclusionExtended-release niacin therapy, in the absence of other lipid-modifying medications, can increase HDL-associated SAA, an acute phase protein associated with HDL dysfunction.

Atherosclerosis: cell biology and lipoproteins.

Lipoproteins have significant role in both the promotion and prevention of atherosclerosis. This brief review will focus on recent reports on relationship between HDL and HDL subclasses and their composition and function, the role of apoC-III in metabolism of triglyceride-rich lipoproteins, the impact of Lipoprotein (a) (Lp(a)) on endothelial cells, and the mechanism of uptake of aggregated LDL by macrophages. The complexity of the protein and lipid content of murine and human HDL and their relationship to its cholesterol efflux capacity have been examined. HDL has also been shown to have both antiatherogenic and proatherogenic properties. The relationship between apoC-III and LPL activity, apoprotein E mediated clearance of triglyceride-rich lipoproteins and the potential importance of apoC-III in the increased risk of cardiovascular disease in type 1 diabetics has been investigated. Oxidized phospholipid in Lp(a) promotes endothelial cells inflammatory and glycolytic responses. TLR4 participates in the uptake of aggregated LDL to contribute to foam cell formation. These studies contribute to our mechanistic understanding of how lipoproteins contribute to atherogenesis and identify potential therapeutic targets.

Food cravings: Associations with dietary intake and metabolic health

Food cravings are a desire for specific foods which, if uncontrolled may lead to excess energy intake and weight gain. However, information on the relation between food cravings, dietary intake, and indices of metabolic health is limited. This study used baseline data from females (n = 229; aged 40.9 ± 0.7 years; BMI 34.7 ± 6.4 kg/m2) who were dependents of active duty and retired military personnel, and enrolled in the Healthy Families Healthy Forces weight loss and maintenance study. Measures obtained included food cravings using the Food Craving Questionnaire-Trait (which provides a habitual and stable measure of food cravings), dietary composition and eating patterns from three 24-h dietary recalls and the Stanford 7-day Physical Activity Recall, body composition from anthropometric measures, cardiometabolic risk factors from blood measures, and demographic information from questionnaires. Linear, quantile, or logistic regression models were used to examine the association of total food craving scores on dietary intake, and indices of metabolic health. In individuals reporting plausible energy intake (n = 146; 2210 ± kcals/day) higher food craving scores were associated with a lower diet quality (P < 0.05), higher eating frequency (P = 0.02), longer daily eating interval (P < 0.05), and a lower likelihood of following a time restricted eating pattern (P = 0.02). Food cravings were also positively associated with BMI (P = 0.03) and waist circumference (P = 0.01), but not with measures of cardiometabolic risk (LDL, HDL, total cholesterol:HDL, triglycerides, glucose, glycated hemoglobin, insulin and C-reactive protein concentrations, blood pressure, metabolic syndrome). Our findings of significant associations of food cravings with lower diet quality, poor eating patterns, and unfavorable body composition strongly support efforts of targeting cravings in behavioral programs for weight management.

Abstract P228: Do Cardiometabolic Risk Profiles Differ Across Race-Ethnicity? An Analysis of the Most Active U.S. Adults in the 2003-2006 NHANES

Introduction: Previous studies have revealed a significant, inverse dose-response relationship between total activity counts/day (TAC/d) and several cardiometabolic risk factors (CMRF). An ongoing line of research is the examination of the contributions of behavioral, environmental, and physiological factors to CMRF differences across race-ethnicity. However, it is unknown if these differences exist among the most physically active adults. Hypothesis: Among the most active U.S. adults, we hypothesize that CMRF measures will differ across race-ethnic groups. Methods: Study sample (n=1,059) included adult (20-79 years of age) participants from the 2003-2006 NHANES who wore an ActiGraph model 7164 accelerometer on the right hip. The top quartile of accelerometer-derived age- and gender-specific TAC/d was used as a cutpoint to define the “most active”. All participants were without T2D (fasting glucose &lt;126 mg/dL, no medication, no self-reported diagnosis) and without CVD (self-report). CMRF included HOMA-IR, fasting insulin and glucose, systolic (SBP) and diastolic blood pressure (DBP), HDL, LDL, triglycerides, BMI, waist circumference (WC) and C-reactive protein (CRP). Multiple linear regression was used to examine CMRF differences between non-Hispanic white (NHW), non-Hispanic black (NHB) and Mexican American (MA) participants. Regression models were adjusted for age, sex, education, smoking, wear time, BMI (except BMI and WC models), objectively-measure MVPA (≥760 counts/min) and race-ethnicity. Results: No significant differences were found in mean TAC/d across race-ethnicity. When compared to NHW, NHB had significantly higher HOMA-IR, fasting insulin, SBP, WC, and BMI. Compared to NHW, MA had significantly higher HOMA-IR, fasting insulin, triglycerides, WC and BMI. When comparing NHB to MA, MA had significantly higher triglycerides and HDL and significantly lower SBP. Conclusions: It has been proposed that the race-ethnic differences in PA participation could be contributing to disparities in elevated CMRF, but even among U.S. adults in the 75th percentile for total activity volume (i.e. TAC/d), race-ethnic differences in CMRF still exist. It is probable that other social, environmental, and genetic factors are responsible for moderating the beneficial effects PA has on CMRF specifically among NHB and MA adults.

Effects of Grape (Vitis vinifera L.) Seed Oil and St John’s Wort (Hypericum perforatum L.) Extract Supplementation into Diets of Laying Hens at Different Levels on Performance, Egg Quality and Some Blood Parameters

This study set out to determine the effects of dietary supplementation of grape seed oil and Hypericum perforatum L. extract to the laying hens (Lohmann White, 40 weeks of age) on performance, egg quality and some blood parameters. For this purpose, a total of 336 hens were randomly distributed to the control and other treatment groups, 12 replicates/group with 4 hens/replication. Birds were fed with basal diet only (control group) and the basal diet supplemented with different levels (100, 200, 300 mg/kg) of grape seed oil (GSO-1, GSO-2, GSO-3) and Hypericum perforatum L. extract (HPE-1, HPE-2, HPE-3). Dietary treatments had no significant effect on performance parameters. GSO-3 and HPE-1 supplemental groups presented with increased shell weight (p&amp;lt;0.01) while only GSO-1 group showed increased egg albumen index (p&amp;lt;0.01) and Haugh unit (p&amp;lt;0.05). Among blood parameters, except for serum HDL and total protein, the other blood parameters (serum triglyceride, total cholesterol, LDL, AST, Ca and P) were not affected by the treatments. In conclusion, results showed a partial improvement in some egg quality traits, however, further studies are needed to fully investigate the beneficial effects of these additives in laying hens reared under different stresses.

The Relationship between the Consumption Pattern of Pokea Clam and Protein with LDL and HDL Levels in Patients with Hypertension

Introduction: This study aims to determine the relationship between the consumption pattern of pokea clam and protein with LDL and HDL levels in patients with hypertension. Method : This study used an observational analysis method with a case control study design. Research location in the area of the Sampara District. The number of samples was 60 people consisting of 30 case samples and 30 control samples using purposive sampling technique. The data was taken using a questionnaire pokea clam consumption pattern, Semi-Quantitative Food Frequency Questionnaire (FFQ-SQ) questionnaire and blood pressure data using mercury sphygmomanometer. Result of the data obtained were processed by analysis of Chi-Square test data with a value of p&lt;0.05 accompanied by an Odd Ratio value. Results: Statistical analysis showed that the relationship between pokea clam consumption patterns (ρ=0,604; OR=1,408) and protein consumption patterns (ρ=0,218; OR=2,051) with LDL levels. Statistical analysis showed that the consumption patterns of pokea with HDL levels (OR= 1.259,p=0.704) and protein consumption patterns with HDL levels (OR=0.889, p=0.839). Conclusion : There were no correlation between pokea clam consumption pattern and protein with LDL and HDL levels in hypertensive patients of Sampara District.

Effects of tibolone or continuous combined oestradiol and norethisterone acetate on lipids, high-density lipoprotein subfractions and apolipoproteins in postmenopausal women in a two-year, randomized, double-blind, placebo-controlled trial.

To compare the effects of (a) tibolone, (b) continuous combined oestrogen plus progestogen and (c) placebo on plasma lipid and lipoprotein markers of cardiovascular risk in healthy postmenopausal women. Randomized, single-centre, placebo-controlled, double-blind study. One hundred and one postmenopausal women were randomized (1:1:1) into one of three groups taking daily 2.5mg tibolone, continuous oral oestradiol-17β 2mg plus norethisterone acetate 1mg daily (E2 /NETA) or placebo. Fasting serum lipid, lipoprotein and apolipoprotein concentrations measured at baseline and after 6, 12 and 24months of treatment. Both tibolone and E2 /NETA lowered plasma total cholesterol concentrations relative to placebo. With tibolone, high-density lipoprotein cholesterol (HDL-C) was reduced (-27% at 24months, P<.001), the greatest effect being in the cholesterol-enriched HDL2 subfraction (-40%, P<.001). Tibolone's effect on HDL concentrations was also apparent in the principal HDL protein component, apolipoprotein AI (-29% at 24months, P<.001). However, there was no significant effect of tibolone on low-density or very low-density lipoprotein cholesterol (LDL-C and VLDL-C, respectively). By contrast, the greatest reduction in cholesterol with E2 /NETA was in LDL-C (-22% at 24months, P=.008). E2 /NETA reduced HDL-C to a lesser extent than tibolone (-12% at 24months, P<.001). Effects on HDL apolipoproteins were similarly diminished relative to tibolone. E2 /NETA had no effect on VLDL-C or on the protein component of LDL, apolipoprotein B. Tibolone reduces serum HDL. E2 /NETA reduces LDL cholesterol but not apolipoprotein B, suggesting decreased cholesterol loading of LDL. Any impact these changes may have on CVD risk needs further investigation.

CORRELATION BETWEEN APOPROTEIN B/APOPROTEIN A-I RATIO WITH HOMA IR VALUE (HOMEOSTATIC MODEL ASSESMENT INSULIN RESISTANCE) IN TYPE 2 DIABETES MELLITUS

Background: Diabetes mellitus (DM) is the seventh leading cause of death in the world (the occuring rate has reached 400 million people). Type2 DM is caused by the body cells’ inability to respond normally to insulin (insulin resistance). Homeostatic Model Assessment-Insuline Resistance (HOMA-IR) is a calculation method which function is to measure the body insulin resistance. Diabetes mellitus can cause lipid metabolism disorders (dyslipidemia) resulting in an increased level of LDL cholesterol and decreased HDL cholesterol. The apoprotein B/apoprotein A-I ratio is the result of comparisons of apoprotein B (LDL protein constituent) and apoprotein A-I (HDL protein constituent). The apo B/apo A-I ratio represents a balance between LDL cholesterol (atherogenic) and HDL (anti-atherogenic). It is astrong signifier in predicting heart disease. Purpose: This study aim to determine the correlation between the apoprotein B/apoprotein A-I ratio with HOMA-IR in patients with type 2 diabetes mellitus. Methods: Observasional, consecutive, 100 people with type 2 diabetes mellitus who is examined in apoprotein B, apoprotein A-I test that calculating the ratio in which ratio are calculated, as well as HOMA-IR in Parahita Clinical Laboratory Surabaya. This study uses Pearson correlation test method with SPSS 22.0 for Windows program. Results: The result of Pearson correlation test between apoprotein B/apoprotein A-I ratio with HOMA-IR in 100 samples is a strong and significant correlation value (r=0,610, p&lt;0,05).Conclusion: There is a strong correlation between the apoprotein B/apoprotein A-I ratio with HOMA-IR in patients with type 2 diabetes mellitus.

Biochemical evaluation of antibacterial activity of short and medium chain fatty acids in broiler

The objective of the present study was to evaluate the antimicrobial effect of short and medium fatty acid chain. Total number of 2000 Cobb broiler chicks (mixed sexes) were commercially purchased from EL Dakahlia poultry company that were 1d old were reared up to 40d of age. Corn and soybean meal based starter and grower diet were supplemented. Chicken were randomly divided in to two main group, 1st group act as normal control, 2nd group was add C12( mixed short and medium fatty acid) in drinking water for 3 day each 8 day at 11, 22 and 33 days age. Blood sample were collected before and after taking C12 treatment for biochemical examination. Supplementation of C12 caused decrease in serum level of AST, ALT, glucose, cholesterol, triglyceride, and pro-inflammatory cytokines as IL-6, increase HDL and total protein. Evaluation of antimicrobial activity of C12.

High Concentration of Medium-Sized HDL Particles and Enrichment in HDL Paraoxonase 1 Associate With Protection From Vascular Complications in People With Long-standing Type 1 Diabetes.

A subset of people with long-standing type 1 diabetes (T1D) appears to be protected from microvascular and macrovascular complications. Previous studies have focused on improved abilities to respond to glucose and its downstream effects as protective mechanisms. It is unclear whether lipoproteins play a role in the vascular health of these people. We therefore determined whether HDL particle concentration, size, function, and/or protein composition associate with protection from vascular complications. We studied two independent cross-sectional cohorts with T1D: the T1D Exchange Living Biobank (n = 47) and the Joslin Medalist Study (n = 100). Some of the subjects had vascular complications, whereas others never exhibited vascular complications, despite an average duration of diabetes in the cohorts of 45 years. We assessed HDL particle size and concentration by calibrated ion mobility analysis, the HDL proteome by targeted mass spectrometry, and HDL function ex vivo by quantifying cholesterol efflux capacity and inhibition of monocyte adhesion to endothelial cells. In both cohorts, people without vascular complications exhibited significantly higher concentrations of medium-sized HDL particles (M-HDL) independently of total and HDL cholesterol levels. While no consistent differences in HDL functions were observed ex vivo, people without vascular complications had higher levels of HDL-associated paraoxonase 1 (PON1), an enzyme that inhibits atherosclerosis in animal models. Elevated concentrations of M-HDL particles and elevated levels of HDL-associated PON1 may contribute to long-term protection from the vascular complications of diabetes by pathways that are independent of total cholesterol and HDL cholesterol.

The HDL lipidome is widely remodeled by fast food versus Mediterranean diet in 4days.

HDL is associated with increased longevity and protection from multiple chronic diseases. The major HDL protein ApoA-I has a half-life of about 4days, however, the effects of diet on the composition of HDL particles at this time scale have not been studied. The objective of this study is to investigate the short term dietary effect on HDL lipidomic composition. In this randomized order cross-over study, ten healthy subjects consumed a Mediterranean (Med) and a fast food (FF) diet for 4days, with a 4-day wash-out between treatments. Lipidomic composition was analyzed in isolated HDL fractions by an untargeted LC-MS method with 15 internal standards. HDL phosphatidylethanolamine (PE) content was increased by FF diet, and 41 out of 170 lipid species were differentially affected by diet. Saturated fatty acids (FAs) and odd chain FA were enriched after FF diet, while very-long chain FA and unsaturated FA were enriched after Med diet. The composition of phosphatidylcholine (PC), triacylglycerol (TG) and cholesteryl ester (CE) were significantly altered to reflect the FA composition of the diet whereas the composition of sphingomyelin (SM) and ceramides were generally unaffected. Results from this study indicate that the HDL lipidome is widely remodeled within 4days of diet change and that certain lipid classes are more sensitive markers of diet whereas other lipid classes are better indicators of non-dietary factors.

HDL subclass proteomic analysis and functional implication of protein dynamic change during HDL maturation

Recent clinical trials reported that increasing high-density lipoprotein-cholesterol (HDL-C) levels does not improve cardiovascular outcomes. We hypothesize that HDL proteome dynamics determine HDL cardioprotective functions. In this study, we characterized proteome profiles in HDL subclasses and established their functional connection. Mouse plasma was fractionized by fast protein liquid chromatography, examined for protein, cholesterial, phospholipid and trigliceride content. Small, medium and large (S/M/L)-HDL subclasseses were collected for proteomic analysis by mass spectrometry. Fifty-one HDL proteins (39 in S-HDL, 27 in M-HDL and 29 in L-HDL) were identified and grouped into 4 functional categories (lipid metabolism, immune response, coagulation, and others). Eleven HDL common proteins were identified in all HDL subclasses. Sixteen, 3 and 7 proteins were found only in S-HDL, M-HDL and L-HDL, respectively. We established HDL protein dynamic distribution in S/M/L-HDL and developed a model of protein composition change during HDL maturation. We found that cholesterol efflux and immune response are essential functions for all HDL particles, and amino acid metabolism is a special function of S-HDL, whereas anti-coagulation is special for M-HDL. Pon1 is recruited into M/L-HDL to provide its antioxidative function. ApoE is incorporated into L-HDL to optimize its cholesterial clearance function. Next, we acquired HDL proteome data from Pubmed and identified 12 replicated proteins in human and mouse HDL particle. Finally, we extracted 3 shared top moleccular pathways (LXR/RXR, FXR/RXR and acute phase response) for all HDL particles and 5 top disease/bio-functions differentially related to S/M/L-HDL subclasses, and presented one top net works for each HDL subclass. We conclude that beside their essencial functions of cholesterol efflux and immune response, HDL aquired antioxidative and cholesterol clearance functions by recruiting Pon1 and ApoE during HDL maturation.

SUN-542 Comparison of Different Muscle Mass Indices for Evaluation of Low Muscle Mass Regarding Muscle Function, Bone Mineral Density and Metabolic Profile in Obese Patients Prior to Bariatric Surgery

Sarcopenic obesity increases the risk of metabolic complications (MC), falls, fractures and even increased mortality. The identification of a low muscle mass (LMM) occurs through the muscle mass index (MMI). The height-adjusted MMI in the elderly is the most used for the diagnosis of sarcopenia (SARC). However, in the young obese subject there is data in the literature favoring the weight-adjusted MMI, due to a better identification of SARC and correlation with MC. Objective: To identify obese patients with low muscle mass (O-LMM) prior to bariatric surgery through three different MMIs regarding muscle function (hand grip (HG) and gait velocity (GV)), bone mineral density (BMD) and metabolic profile. Methods: The cross-sectional study, involving 59 obese women of a public hospital in Brazil, was conducted. The sample was divided into two groups according to the presence of O-LMM and obese patients with normal muscle mass (O-NMM) for each IMM. We considered O-LMM patients who were in the lowest quintile for each IMM and the patients who were in the other quintiles were considered as O-NMM. The body composition was evaluated by bio-impedance (inbody-370), multifrequency (5, 50, 250 HZ), with fasting of 12 hours and BMD by lunar densitometer prodigy advance. To estimate muscle mass, the following MMIs were used: height-adjusted MMI (MMI-height): appendicular muscle mass (AMM) / height2; MMI adjusted for weight (MMI-weight): AMM / weight x 100 and MMI adjusted for body mass index (MMI-BMI): MMA / BMI. The HG was evaluated by jamar dynamometer (3 measurements with interval of 30 seconds between them) and the physical performance by the GV for 6 minutes. Fasting glycemia, HbA1c, HOMA-IR, insulin, total cholesterol, HDL, LDL, triglycerides and high sensitivity quantitative C-reactive protein were assessed. Results: The participants had a mean age of 39.53 ± 8,99 years, weight: 108.60 ± 13.86 kg and BMI: 42.6 ± 4.64 kg / m2. O-LMM were identified at 30.5% (n = 18) by MMI-weight, and also at 20.33% by MMI-BMI and MMI-height. Patients in the lowest quintile for the MMI-weight had a lower HG (24.16 x 30.69 kg, p = 0.000), lower BMD in L1-L4 (1.17 x 1.27 g / cm2, p = 0.001), in the femoral neck (FN) ( 1.04 x 1.14 g / cm2, p = 0.012) and in the total femur (TF) (1.10 x 1.19 g / cm2, p = 0.039), respectively, but without significant difference for GV. For MMI-BMI, O-LMM presented lower GV (0.93 x 1.06 m / s, p = 0.017) and HG (23.19 x 30.22 kg, p = 0.000), however without significant difference for BMD. The O-LMM identified by the MMI-height had lower BMD in FN (1.01 x 1.13 g / cm2, p = 0.009) and TF (1.06 x 1.19 g / cm2, p = 0.012), with no significant difference for muscle function. Metabolic profile was not worse in the O-LMM by the three MMIs. Conclusion: The MMI-weight identifies more O-LMM patients than the other MMI. The O-LMM diagnosed by MMI-weight had lower BMD in all sites and lower HG than O-NMM, possibly being a better IMM to diagnose SARC in obese patients.

From HDL-cholesterol to HDL-function: cholesterol efflux capacity determinants.

The validity of HDL-cholesterol (HDL-C) elevation as a therapeutic target has been questioned, in comparison to enhancing HDL functionality. Cholesterol efflux capacity (CEC) is an in-vitro assay that measures the ability of an individual's HDL to promote cholesterol efflux from cholesterol donor cells such as macrophages. CEC of HDL is a predictor of cardiovascular risk independent of HDL-C levels. However, molecular determinants of CEC and the effects of diseases and therapeutic interventions on CEC have not been completely defined. We review here recent findings on elevated HDL-C and disease risk, as well as determinants of CEC, from genetics and proteomics to pathophysiology and therapeutic interventions that contribute to our understanding of CEC as a biomarker of HDL functionality. Elevated HDL-C levels are not always protective against cardiovascular disease and mortality. CEC is a heritable trait, and genetic polymorphisms in genes involved in HDL and triglycerides metabolism are associated with CEC. Multiple HDL proteins correlate positively with CEC levels and inversely with noncalcified plaque burden. Differences in CEC assays that make comparisons between studies difficult are also emphasized. CEC should be measured in clinical trials of lipid-modifying and anti-inflammatory therapies to determine whether increases are cardioprotective.

Serum interleukin 15 in anorexia nervosa: Comparison to normal weight and obese girls

Background: Interleukin 15 (IL-15) plays a key role in the muscle-fat interaction, reducing adipose tissue mass without changes in the lean body mass and reduction of food intake. Here we assess serum IL-15 levels in girls with anorexia nervosa (AN) relative to obese and normal weight female adolescents.Methods: Serum IL-15 concentrations were evaluated using a commercially available ELISA kit in 32 Polish girls with restrictive AN, 29 girls with obesity (O), and 21 healthy controls (C). Anthropometric measurements (weight, height, BMI) and laboratory assays (serum fasting glucose, insulin, HOMA-IR, total cholesterol, HDL, LDL, triglycerides, and C-reactive protein (CRP)) were performed.Results: Mean serum IL-15 in the AN group was significantly higher than in C, but lower than in O. In all examined girls, significant positive correlations between IL-15 and body weight, BMI, insulin, HOMA, LDL, triglycerides and CRP were noted. We also observed an inverse relationship between IL-15 and HDL.Conclusions: Our study demonstrated that serum IL-15 concentrations in adolescent girls with AN and obesity are significantly elevated in comparison to normal weight controls. However, the role of IL-15 in the pathogenesis of AN and obesity remains still unclear.

Abstract MP41: A Diet High in Carbohydrate and Low in Fat Alters the HDL Proteome and Metabolism of 9 HDL Proteins in Humans

Introduction: When dietary carbohydrate replaces fat, HDL cholesterol (HDL-C) and the primary HDL protein apolipoprotein A1 (apoA1) decrease. The proportion in plasma of large HDL2 decreases while small HDL3 increases. These findings suggest that diet affects metabolically important attributes of HDL that produce the size changes. We studied in humans the effect of dietary carbohydrate and unsaturated fat on the HDL proteome and metabolism of 9 HDL proteins across 5 HDL sizes. Methods and Results: Twelve participants were placed on a healthy, controlled diet high in unsaturated fat (HF) or high in carbohydrate (HC) in a randomized crossover design. At the end of each 4-week diet period, subjects were infused with a stable isotope tracer (D3-Leu) in order to label all newly synthesized HDL proteins. Blood samples were collected and tracer was followed for 70 hrs post-infusion. ApoA1-HDL was isolated by immunoaffinity purification, separated into 5 HDL particle sizes, and prepared for analysis by mass spectrometry. We used label free quantification to characterize the HDL proteome. The proteome composition and distribution across the 5 HDL sizes were remarkably conserved in all subjects on both diets. Diet altered the abundance of several proteins on the major HDL sizes alpha2 and alpha3. The HC diet increased proteins involved in lipid metabolism (apoC3, apoA2) and decreased antioxidant (PON1, PON3) and protease inhibitor (SERPINA3, SERPING1) proteins. We also monitored the metabolism of 9 proteins that likely affect HDL metabolism - apoA1, apoA2, apoA4, apoC3, apoE, apoJ, apoL1, apoM and LCAT. We used parallel reaction monitoring and XPI software to measure the amount of D3-Leu tracer over time in these 9 proteins across the 5 HDL sizes. We found that the HC diet increased apoA2 and apoJ and decreased apoA1 pool sizes on large HDL. The HC diet also increased apoM turnover in large HDL, and apoA1, apoA2, and apoE turnover across the HDL size range. Conclusions: Dietary carbohydrate when it replaces unsaturated fat alters the HDL proteome and metabolism of several HDL proteins on specific HDL sizes. Carbohydrate increases the abundance of proteins involved in lipid metabolism, decreases antioxidant and protease inhibitor proteins, and accelerates turnover of apoA1, apoA2, apoE, and apoM. This study suggests that diet modulates HDL function by affecting HDL composition and the metabolism of major HDL proteins.

Genetic control of the mouse HDL proteome defines HDL traits, function, and heterogeneity

HDLs are nanoparticles with more than 80 associated proteins, phospholipids, cholesterol, and cholesteryl esters. The potential inverse relation of HDL to coronary artery disease (CAD) and the effects of HDL on myriad other inflammatory conditions warrant a better understanding of the genetic basis of the HDL proteome. We conducted a comprehensive genetic analysis of the regulation of the proteome of HDL isolated from a panel of 100 diverse inbred strains of mice (the hybrid mouse diversity panel) and examined protein composition and efflux capacity to identify novel factors that affect the HDL proteome. Genetic analysis revealed widely varied HDL protein levels across the strains. Some of this variation was explained by local cis-acting regulation, termed cis-protein quantitative trait loci (QTLs). Variations in apoA-II and apoC-3 affected the abundance of multiple HDL proteins, indicating a coordinated regulation. We identified modules of covarying proteins and defined a protein-protein interaction network that describes the protein composition of the naturally occurring subspecies of HDL in mice. Sterol efflux capacity varied up to 3-fold across the strains, and HDL proteins displayed distinct correlation patterns with macrophage and ABCA1-specific cholesterol efflux capacity and cholesterol exchange, suggesting that subspecies of HDL participate in discrete functions. The baseline and stimulated sterol efflux capacity phenotypes were associated with distinct QTLs with smaller effect size, suggesting a multigenetic regulation. Our results highlight the complexity of HDL particles by revealing the high degree of heterogeneity and intercorrelation, some of which is associated with functional variation, and support the concept that HDL-cholesterol alone is not an accurate measure of HDL’s properties, such as protection against CAD.

Diabetes-induced Alterations in HDL Subfractions Distribution.

Diabetes mellitus (DM) due to its increasing prevalence and associated morbidity and mortality has become a serious public health problem. In DM, HDL may lose its beneficial features and become proatherogenic due to its altered biological activity thus increasing cardiovascular risk. The aim of this study was to assess the influence of the presence of diabetes mellitus type 2 and its duration on the distribution of HDL subfractions. Moreover, the effect of statin treatment on HDL subfraction share was analysed in this study. The study group consisted of 50 patients with newly diagnosed DM and 50 persons with DM for longer than 10 years while the control group consisted of 50 healthy volunteers. HDL subfractions were analysed with the use of Lipoprint. We demonstrated progressive worsening of heart functioning and impairment of its structure in the course of diabetes mellitus. Moreover, we observed that HDL-6 subfraction and intermediate HDL fraction are lowest in the group with advanced DMt2 compared to the group with newly diagnosed DM and a healthy control group. Finally, the results of our study indicated the effect of statin treatment on HDL subfractions that seems not to be advantageous. It seems that in patients with diabetes mellitus compromised antiatherogenic properties of HDL, as a result of oxidative modification and glycation of the HDL protein as well as the transformation of the HDL proteome into a proinflammatory protein, increase cardiovascular risk.