Per-Particle Triglyceride-Rich Lipoproteins Imply Higher Myocardial Infarction Risk Than Low-Density Lipoproteins: Copenhagen General Population Study.

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ANGPTL3 Inhibition With Evinacumab Results in Faster Clearance of IDL and LDL apoB in Patients With Homozygous Familial Hypercholesterolemia-Brief Report.

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Scavenging of reactive dicarbonyls with 2-hydroxybenzylamine reduces atherosclerosis in hypercholesterolemic Ldlr-/- mice.

Lipid peroxidation generates reactive dicarbonyls including isolevuglandins (IsoLGs) and malondialdehyde (MDA) that covalently modify proteins. Humans with familial hypercholesterolemia (FH) have increased lipoprotein dicarbonyl adducts and dysfunctional HDL. We investigate the impact of the dicarbonyl scavenger, 2-hydroxybenzylamine (2-HOBA) on HDL function and atherosclerosis in Ldlr-/- mice, a model of FH. Compared to hypercholesterolemic Ldlr-/- mice treated with vehicle or 4-HOBA, a nonreactive analogue, 2-HOBA decreases atherosclerosis by 60% in en face aortas, without changing plasma cholesterol. Ldlr-/- mice treated with 2-HOBA have reduced MDA-LDL and MDA-HDL levels, and their HDL display increased capacity to reduce macrophage cholesterol. Importantly, 2-HOBA reduces the MDA- and IsoLG-lysyl content in atherosclerotic aortas versus 4-HOBA. Furthermore, 2-HOBA reduces inflammation and plaque apoptotic cells and promotes efferocytosis and features of stable plaques. Dicarbonyl scavenging with 2-HOBA has multiple atheroprotective effects in a murine FH model, supporting its potential as a therapeutic approach for atherosclerotic cardiovascular disease.

Apolipoprotein CIII Deficiency Protects Against Atherosclerosis in Knockout Rabbits.

OBJECTIVE: Apo (apolipoprotein) CIII mediates the metabolism of triglyceride (TG)-rich lipoproteins. High levels of plasma apoCIII are positively correlated with the plasma TG levels and increase the cardiovascular risk. However, whether apoCIII is directly involved in the development of atherosclerosis has not been fully elucidated. Approach and Results: To examine the possible roles of apoCIII in lipoprotein metabolism and atherosclerosis, we generated apoCIII KO (knockout) rabbits using ZFN (zinc finger nuclease) technique. On a normal standard diet, apoCIII KO rabbits exhibited significantly lower plasma levels of TG than those of WT (wild type) rabbits while total cholesterol and HDL (high-density lipoprotein) cholesterol levels were unchanged. Analysis of lipoproteins isolated by sequential ultracentrifugation revealed that reduced plasma TG levels in KO rabbits were accompanied by prominent reduction of VLDLs (very-low-density lipoproteins) and IDLs (intermediate-density lipoproteins). In addition, KO rabbits showed faster TG clearance rate after intravenous fat load than WT rabbits. On a cholesterol-rich diet, KO rabbits exhibited constantly and significantly lower levels of plasma total cholesterol and TG than WT rabbits, which was caused by a remarkable reduction of ß-VLDLs-the major atherogenic lipoproteins. ß-VLDLs of KO rabbits showed higher uptake by cultured hepatocytes and were cleared faster from the circulation than ß-VLDLs isolated from WT rabbits. Both aortic and coronary atherosclerosis was significantly reduced in KO rabbits compared with WT rabbits. CONCLUSIONS: These results indicate that apoCIII deficiency facilitates TG-rich lipoprotein catabolism, and therapeutic inhibition of apoCIII expression may become a novel means not only for the treatment of hyperlipidemia but also for atherosclerosis.

Effect of the Fat Eaten at Breakfast on Lipid Metabolism: A Crossover Trial in Women with Cardiovascular Risk.

Recent studies point out that not only the daily intake of energy and nutrients but the time of day when they are ingested notably regulates lipid metabolism and cardiovascular risk (CVR). Therefore, the aim of the study was to assess if the type of fat ingested at breakfast can modify lipid metabolism in women with CVR. A randomized, crossover clinical trial was performed. Sixty volunteers were randomly assigned to a (A) polyunsaturated fatty acid (PUFA)-rich breakfast, (B) saturated fatty acid (SFA)-rich breakfast, or (C) monounsaturated fatty acid (MUFA)-rich breakfast. Plasma lipoprotein and apolipoprotein subfractions were determined. Our data showed that the PUFA-rich breakfast decreased lipoprotein (a) (Lp(a)), very low-density lipoproteins (VLDL), and intermediate-density lipoproteins (IDL), and increased high-density lipoproteins (HDL). A similar trend was observed for the MUFA-rich breakfast, whereas the SFA-rich breakfast, although it decreased VLDL, also increased IDL and reduced HDL. The PUFA-rich breakfast also decreased ß-lipoproteins and apolipoprotein-B. In summary, varying the type of fat eaten at breakfast is enough to significantly modify the lipid metabolism of women with CVR, which can be of great relevance to establish new therapeutic strategies for the treatment of these subjects.

Gender differences in LDL and HDL subfractions in atherogenic and nonatherogenic phenotypes.

OBJECTIVES: The aim of our study was to examine the role of low density lipoprotein (LDL)-subfractions in individuals with the atherogenic and non-atherogenic phenotype and the gender differences in lipoprotein subfractions including small dense LDL (sdLDL) and small high density lipoprotein (sHDL) subfractions representing the most atherogenic lipoprotein subfractions. DESIGN & METHODS: 35 persons in the atherogenic group (AG) (with sdLDL3-7 subfractions ≥6 mg/dl) and 104 individuals in the non-atherogenic group (NAG) (sdLDL3-7 subfractions <6 mg/dl) were included in our study. To analyze plasma lipoprotein subfractions, a polyacrylamide gel electrophoresis-the Lipoprint system was used. RESULTS: Males compared to females in the AG had significantly higher levels of atherogenic lipoprotein subfractions such as HDL8, HDL9 and HDL10. All participants in AG had significantly lower levels of intermediate density lipoprotein IDL-A than those in NAG but significantly higher levels of IDL-B and IDL-C. Males in the AG compared to NAG had significantly lower levels of LDL1 and higher levels of LDL2 and LDL3-7 subfractions. In the NAG LDL2 positively correlated with sHDL subfractions while in the AG with the large HDL subfraction. CONCLUSION: Results of our study demonstrate more atherogenic profile in males compared to females and a double role of LDL2 subfraction in the atherogenic process depending on the phenotype (atherogenic/non-atherogenic) of individuals.

A third of nonfasting plasma cholesterol is in remnant lipoproteins: Lipoprotein subclass profiling in 9293 individuals.

BACKGROUND AND AIMS: Increased concentrations of calculated remnant cholesterol in triglyceride-rich lipoproteins are observationally and genetically, causally associated with increased risk of ischemic heart disease; however, when measured directly, the fraction of plasma cholesterol present in remnant particles is unclear. We tested the hypothesis that a major fraction of plasma cholesterol is present in remnant lipoproteins in individuals in the general population. METHODS: We examined 9293 individuals from the Copenhagen General Population Study using nuclear magnetic resonance spectroscopy measurements of total cholesterol, free- and esterified cholesterol, triglycerides, phospholipids, and particle concentration. Fourteen subclasses of decreasing size and their lipid constituents were analysed: six subclasses were very low-density lipoprotein (VLDL), one intermediate-density lipoprotein (IDL), three low-density lipoprotein (LDL), and four subclasses were high-density lipoprotein (HDL). Remnant lipoproteins were VLDL and IDL combined. RESULTS: Mean nonfasting cholesterol concentration was 1.84 mmol/L (72 mg/dL) for remnants, 2.01 mmol/L (78 mg/dL) for LDL, and 1.83 mmol/L (71 mg/dL) for HDL, equivalent to remnants containing 32% of plasma total cholesterol. Of 14 lipoprotein subclasses, large LDL and IDL were the ones containing most of plasma cholesterol. The plasma concentration of remnant cholesterol was from ∼1.4 mmol/L (54 mg/dL) at age 20 to ∼1.9 mmol/L (74 mg/dL) at age 60. Corresponding values for LDL cholesterol were from ∼1.5 mmol/L (58 mg/dL) to ∼2.1 mmol/L (81 mg/dL). CONCLUSIONS: Using direct measurements, one third of total cholesterol in plasma was present in remnant lipoproteins, that is, in the triglyceride-rich lipoproteins IDL and VLDL.

Effect of 1- and 2-Month High-Dose Alpha-Linolenic Acid Treatment on 13 C-Labeled Alpha-Linolenic Acid Incorporation and Conversion in Healthy Subjects.

SCOPE: The study aims at identifying 1) the most sensitive compartment among plasma phospholipids, erythrocytes, and LDL for studying alpha-linolenic acid (ALA) conversion, and 2) whether ALA incorporation and conversion is saturable after administration of 13 C-labeled ALA-rich linseed oil (LO). The effect of a daily intake of 7 g nonlabeled LO (>43% w/w ALA) for 1 month after bolus administration of 7 g 13 C-labeled LO on day 1, and for 2 months after bolus administration of 7 g 13 C-labeled LO on day 1 and day 29 on 13 C-ALA incorporation and conversion into its higher homologs is investigated in healthy volunteers. METHODS AND RESULTS: Incorporation and conversion of LO-derived 13 C-labeled ALA is quantified by applying compartmental modeling. After bolus administration, a fractional conversion of approximately 30% from 13 C-ALA to 13 C-DHA is calculated as reflected by the LDL compartment. Treatment with LO for 8 weeks induces a mean reduction of 13 C-ALA conversion to 13 C-DHA by 48% as reflected by the LDL compartment, and a mean reduction of the 13 C-ALA incorporation into LDL by 46%. CONCLUSION: A 2-month dietary intake of a high dose of LO is sufficient to reach saturation of ALA incorporation into LDL particles, which are responsible for ALA distribution in the body.

Lipoprotein particle sizes in patients undergoing kidney transplantation.

Asymptomatic atherosclerotic disease is prevalent in the middle-aged group of kidney transplant recipients. In order to improve the estimation of their cardiovascular risk, dyslipidaemia pattern is very important to be evaluated. Knowledge of the lipid particle spectrum in patients undergoing kidney transplantation could help the clinicians to timely start intervention and prevention of atherosclerosis with an early hypolipidemic statin treatment (Tab. 2, Ref. 20).

Low IDL-B and high LDL-1 subfraction levels in serum of ALS patients.

INTRODUCTION: Converging evidence highlights that lipid metabolism plays a key role in ALS pathophysiology. Dyslipidemia has been described in ALS patients and may be protective but peripheral lipoprotein subclasses have never been studied. MATERIAL AND METHODS: We collected sera from 30 ALS patients and 30 gender and age-matched controls. We analyzed 11 distinct lipoprotein subclasses by linear polyacrylamide gel electrophoresis (Lipoprint, Quantimetrix Corporation, USA). We also measured lipoprotein (a), apolipoprotein B, and apolipoprotein E levels. RESULTS: ALS patients had significant higher total cholesterol, HDL-cholesterol, and LDL-cholesterol levels than controls (p<0.0001, p=0.0007, and p=0.0065, respectively). The LDL-1 subfraction concentration was higher (1.03±0.41 vs. 0.71±0.28mmol/L; p=0.0006) and the IDL-B subfraction lower (6.5±2% vs. 8.0±2%; p=0.001) in ALS patients than controls. DISCUSSION: Our preliminary work confirmed the association between ALS and dyslipidemia. The low IDL-B levels may explain the hepatic steatosis frequently reported in ALS. The high levels of the cholesterol-rich LDL-1 subfraction is consistent with previously reported hypercholesterolemia. CONCLUSION: This study describes, for the first time, the distribution of serum lipoproteins in ALS patients, with low IDL-B and high LDL-1 subfraction level.

High-quality fish oil has a more favourable effect than oxidised fish oil on intermediate-density lipoprotein and LDL subclasses: a randomised controlled trial.

Fish oil (FO) supplementation reduces the risk of CVD. However, it is not known if FO of different qualities have different effects on lipoprotein subclasses in humans. We aimed at investigating the effects of oxidised FO and high-quality FO supplementation on lipoprotein subclasses and their lipid concentrations in healthy humans. In all, fifty-four subjects completed a double-blind randomised controlled intervention study. The subjects were randomly assigned to receive high-quality FO (n 17), oxidised FO (n 18) or high-oleic sunflower oil capsules (HOSO, n 19) for 7 weeks. The concentration of marine n-3 fatty acids was equal in high-quality FO and oxidised FO (1·6 g EPA+DHA/d). The peroxide value (PV) and anisidine value (AV) were 4 mEq/kg and 3 in high-quality FO and HOSO, whereas the PV and AV in the oxidised FO were 18 mEq/kg and 9. Blood samples were collected at baseline and end of study. NMR spectroscopy was applied for the analysis of lipoprotein subclasses and their lipid concentrations. High-quality FO reduced the concentration of intermediate-density lipoprotein (IDL) particles and large, medium and small LDL particles, as well as the concentrations of total lipids, phospholipids, total cholesterol, cholesteryl esters and free cholesterol in IDL and LDL subclasses compared with oxidised FO and HOSO. Hence, high-quality FO and oxidised FO differently affect lipid composition in lipoprotein subclasses, with a more favourable effect mediated by high-quality FO. In future trials, reporting the oxidation levels of FO would be useful.

Effect of ezetimibe on low- and high-density lipoprotein subclasses in sitosterolemia.

BACKGROUND AND AIMS: Sitosterolemia displays high plasma total sterols [high plant sterols (PS) + normal to high total cholesterol (TC)] with normal to moderately elevated low-density lipoprotein (LDL) levels. High LDL, intermediate-density lipoprotein (IDL) and very low-density lipoprotein (VLDL) particles, low high-density lipoprotein (HDL), and increased non-HDL and the ratios of TC and triglycerides (TG) to HDL can increase the risk for atherosclerosis. Ezetimibe (EZE) can reduce plasma PS and TC levels in sitosterolemia, but its effect on lipoprotein subclasses has not been previously reported. METHODS: Sitosterolemia patients (n = 8) were taken off EZE for 14 weeks (OFF EZE) and placed on EZE (10 mg/d) for 14 weeks (ON EZE). Serum lipids were measured enzymatically and lipoprotein subclasses were assessed by polyacrylamide gel electrophoresis. RESULTS: EZE reduced (p < 0.05) total sterols (-12.5 ± 4.1%) and LDL-sterol (-22.7 ± 5.7%) and its sterol mass of large VLDL (-24.4 ± 4.5%), VLDL remnants (-21.1 ± 7.9%) and large IDL (-22.4 ± 7.2%) compared to OFF EZE. EZE did not affect large LDL subclasses or mean LDL particle size (273.8 ± 0.6 vs. 274.6 ± 0.3 Å). EZE increased HDL-sterol (25.5 ± 8.0%, p = 0.008) including intermediate (34 ± 14%, p = 0.02) and large (33 ± 16%, p = 0.06) HDL. EZE reduced non-HDL-sterol (-21.8± 5.0%), total sterols/HDL (-28.2 ± 5.5%) and TG/HDL (-27.4 ± 6.5%, all p < 0.01). CONCLUSIONS: EZE improves VLDL and HDL subfraction distribution, thereby reducing the atherogenic lipid profile, thus providing potential clinical benefit in sitosterolemia beyond TC and PS reduction.

Serum macrophage migration inhibitory factor levels are associated with infarct volumes and long-term outcomes in patients with acute ischemic stroke.

PURPOSE: Previous studies have shown that macrophage migration inhibition factor (MIF) plays a significant role in stroke. The aim of this study was to investigate the association of the serum MIF level with both infarct volume and long-term outcome in patients with acute ischemic stroke (AIS). METHODS: This study included 146 patients who were identified within 24 h of first experiencing AIS symptoms. Serum MIF levels were tested at the time of admission and three months later. Logistic regression was used to evaluate the risk and long-term outcome of stroke according to serum MIF level. RESULTS: Serum MIF levels were only higher in acute-stage AIS patients compared with those of the normal controls (p < 0.0001). Chronic-stage serum MIF levels were significantly lower than acute-stage serum MIF levels (p < 0.001) and were similar to serum MIF levels in the controls (p = 0.392). The serum MIF level was positively associated with infarct volume (r = 0.5515, p < 0.0001) and NIHSS score (r = 0.5190, p < 0.0001). After adjusting for other significant outcome predictors, the serum MIF level was an independent predictor of long-term outcome, with an adjusted OR of 1.113 (p = 0.005, 95% CI: 1.051-1.238). CONCLUSIONS: This study demonstrated that serum MIF levels were significantly increased after AIS. Serum MIF levels at admission were positively correlated with infarct volume and long-term outcome in patients with AIS. The serum MIF level could serve as a useful prognostic marker in patients with AIS.

Do HDL and LDL subfractions play a role in atherosclerosis in end-stage renal disease (ESRD) patients?

BACKGROUND: Significantly increased cardiovascular mortality in patients with chronic kidney (CKD) disease cannot be explained by traditional risk factors. Recent studies revealed that the quality of HDL and LDL cholesterol may be more important than their serum levels. The aim of this study was to assess which LDL and HDL subfractions were more abundant in end-stage renal disease (ESRD) patients and to analyse whether subfraction distribution could be associated with accelerated atherosclerotic processes. METHODS: This study included 50 ESRD patients undergoing dialysis and 20 healthy volunteers. LDL and HDL subfractions were analysed in serum with the use of Lipoprint system. All patients had intima-media thickness (IMT) measured. RESULTS: Statistically significant differences in subfractions between control and study group were observed in case of: HDL1 (p < 0.0001), HDL2 (p = 0.009), HDL3 (p < 0.0001), HDL4 (p = 0.003), HDL5 (p = 0.01), HDL7 (p < 0.0001), HDL8 (p < 0.0001), HDL9 (p < 0.0001), HDL10 (p < 0.0001), large HDL (p < 0.0001), HDL Small (p < 0.0001) as well as IDL-B (p = 0.014), IDLA (p = 0.011), LDL2 (p = 0.007). Significant differences were also observed in HDL and LDL subfraction distribution between haemodialysis patients with normal and increased IMT: HDL6 (p = 0.020), HDL Large (HDL1-3) (p = 0.017), HDL Intermediate (HDL4-7) (p = 0.017). CONCLUSIONS: This study revealed that ESRD influenced HDL subfractions. In HD patients, large HDL subfractions are more abundant while small HDL fraction is more frequent in healthy persons. It failed to show the influence of end-stage disease on LDL subfraction levels. Shift in HDL subfractions might be responsible for the increased risk of atherosclerosis in CKD patients.

Comprehensive assessment of lipoprotein subfraction profiles according to glucose metabolism status, and association with insulin resistance in subjects with early-stage impaired glucose metabolism.

BACKGROUND: Early detection of atherogenic dyslipidemia is crucial. We investigated lipoprotein subfraction parameters according to glucose metabolism status. METHODS: We recruited 1255 lipid-lowering drug-naïve subjects with normal fasting glucose (NFG; n=200, 15.9%), impaired fasting glucose (IFG; n=443, 35.3%), or type 2 diabetes (T2D; n=612, 48.8%). Lipoprotein subfractions (1-7) were determined by polyacrylamide gel electrophoresis, separating low-density lipoprotein (LDL) into large buoyant LDL (lbLDL, LDL1-2) and small dense LDL (sdLDL, LDL3-7). Lipoprotein subfraction parameters including the sdLDL% (LDL3-7/LDL1-7), the sdLDL/lbLDL ratio (LDL3-7/LDL1-2), and weighted LDL subfraction (LDLSF) scores, were compared between groups. Their associations with insulin resistance, estimated using the homeostasis model assessment of insulin resistance, were examined. RESULTS: The concentrations of sdLDL particles were significantly higher in subjects with T2D and IFG than in those with NFG (15.78±13.47mg/dl and 14.60±14.33mg/dl, respectively, vs. 12.22±12.31mg/dl). Compared with those with NFG, subjects with IFG or T2D had significantly a higher sdLDL% (15.98±15.26% vs. 19.50±16.21% or 21.46±16.81%, respectively), a higher sdLDL/lbLDL ratio (0.24±0.30 vs. 0.31±0.37 or 0.35±0.39), and a higher LDLSF score (2.08±0.91 vs. 2.30±1.14 or 2.36±1.17). These lipoprotein subfraction parameters had stronger associations with insulin resistance compared to conventional lipid profiles in the IFG and T2D groups. CONCLUSIONS: Atherogenic dyslipidemia is initiated in an early stage of impaired glucose metabolism, when early intervention might be required.

Low-Density Lipoprotein Receptor-Dependent and Low-Density Lipoprotein Receptor-Independent Mechanisms of Cyclosporin A-Induced Dyslipidemia.

OBJECTIVE: Cyclosporin A (CsA) is an immunosuppressant commonly used to prevent organ rejection but is associated with hyperlipidemia and an increased risk of cardiovascular disease. Although studies suggest that CsA-induced hyperlipidemia is mediated by inhibition of low-density lipoprotein receptor (LDLr)-mediated lipoprotein clearance, the data supporting this are inconclusive. We therefore sought to investigate the role of the LDLr in CsA-induced hyperlipidemia by using Ldlr-knockout mice (Ldlr(-/-)). APPROACH AND RESULTS: Ldlr(-/-) and wild-type (wt) C57Bl/6 mice were treated with 20 mg/kg per d CsA for 4 weeks. On a chow diet, CsA caused marked dyslipidemia in Ldlr(-/-) but not in wt mice. Hyperlipidemia was characterized by a prominent increase in plasma very low-density lipoprotein and intermediate-density lipoprotein/LDL with unchanged plasma high-density lipoprotein levels, thus mimicking the dyslipidemic profile observed in humans. Analysis of specific lipid species by liquid chromatography-tandem mass spectrometry suggested a predominant effect of CsA on increased very low-density lipoprotein-IDL/LDL lipoprotein number rather than composition. Mechanistic studies indicated that CsA did not alter hepatic lipoprotein production but did inhibit plasma clearance and hepatic uptake of [(14)C]cholesteryl oleate and glycerol tri[(3)H]oleate-double-labeled very low-density lipoprotein-like particles. Further studies showed that CsA inhibited plasma lipoprotein lipase activity and increased levels of apolipoprotein C-III and proprotein convertase subtilisin/kexin type 9. CONCLUSIONS: We demonstrate that CsA does not cause hyperlipidemia via direct effects on the LDLr. Rather, LDLr deficiency plays an important permissive role for CsA-induced hyperlipidemia, which is associated with abnormal lipoprotein clearance, decreased lipoprotein lipase activity, and increased levels of apolipoprotein C-III and proprotein convertase subtilisin/kexin type 9. Enhancing LDLr and lipoprotein lipase activity and decreasing apolipoprotein C-III and proprotein convertase subtilisin/kexin type 9 levels may therefore provide attractive treatment targets for patients with hyperlipidemia receiving CsA.

Complex effects of inhibiting hepatic apolipoprotein B100 synthesis in humans.

Mipomersen is a 20mer antisense oligonucleotide (ASO) that inhibits apolipoprotein B (apoB) synthesis; its low-density lipoprotein (LDL)-lowering effects should therefore result from reduced secretion of very-low-density lipoprotein (VLDL). We enrolled 17 healthy volunteers who received placebo injections weekly for 3 weeks followed by mipomersen weekly for 7 to 9 weeks. Stable isotopes were used after each treatment to determine fractional catabolic rates and production rates of apoB in VLDL, IDL (intermediate-density lipoprotein), and LDL, and of triglycerides in VLDL. Mipomersen significantly reduced apoB in VLDL, IDL, and LDL, which was associated with increases in fractional catabolic rates of VLDL and LDL apoB and reductions in production rates of IDL and LDL apoB. Unexpectedly, the production rates of VLDL apoB and VLDL triglycerides were unaffected. Small interfering RNA-mediated knockdown of apoB expression in human liver cells demonstrated preservation of apoB secretion across a range of apoB synthesis. Titrated ASO knockdown of apoB mRNA in chow-fed mice preserved both apoB and triglyceride secretion. In contrast, titrated ASO knockdown of apoB mRNA in high-fat-fed mice resulted in stepwise reductions in both apoB and triglyceride secretion. Mipomersen lowered all apoB lipoproteins without reducing the production rate of either VLDL apoB or triglyceride. Our human data are consistent with long-standing models of posttranscriptional and posttranslational regulation of apoB secretion and are supported by in vitro and in vivo experiments. Targeting apoB synthesis may lower levels of apoB lipoproteins without necessarily reducing VLDL secretion, thereby lowering the risk of steatosis associated with this therapeutic strategy.

Chronic consumption of an inositol-enriched carob extract improves postprandial glycaemia and insulin sensitivity in healthy subjects: A randomized controlled trial.

BACKGROUND & AIMS: Inositols are thought to be mediators of the insulin signalling pathway. We assessed the effects of inositols on glycaemic control in fasting and postprandial states and evaluated lipoprotein profile and LDL particle size in healthy population. METHODS: A 12-week double-blind clinical trial was performed with forty healthy subjects administered either an inositol-enriched beverage (IEB) -containing 2.23 g of inositols in 250 ml- or a sucrose-sweetened beverage (SB) twice a day. Anthropometric measurements, fasting glucose levels, insulin and HOMA-IR index, lipoprotein profile and postprandial glucose concentrations (measured using the continuous glucose monitoring system (CGMS)) were recorded throughout the intervention period. RESULTS: Following the 12-week trial subjects receiving the IEB exhibited a significant decrease in insulin, HOMA-IR and Apo B and an increase in LDL particle size, whereas the SB group showed increases in BMI and fasting glucose concentration. Analysis of postprandial glucose levels at breakfast, lunch and dinner revealed a mean reduction of glucose of ≈14% and a significant reduction in the area under the curve at 24 h after consumption of the IEB. CONCLUSIONS: Our results show that chronic IEB supplementation induces a significant improvement in carbohydrated metabolism parameters in healthy subjects.

Ghrelin in the pilosebaceous unit: alteration of ghrelin in patients with acne vulgaris.

BACKGROUND: Ghrelin in the pilosebaceous tissues of human skin and ghrelin levels in patients with acne vulgaris have not yet been investigated. OBJECTIVE: The purpose of this study was to screen ghrelin immunoreactivity by immunohistochemistry in human pilosebaceous tissues of human skin and also to determine the quantities of ghrelin in the serum of the patients with acne vulgaris. METHODS: 30 patients presenting with acne vulgaris and 30 control subjects participated in this study. Ghrelin levels were determined by enzyme linked immunosorbent assay (ELISA). Human hair follicles and sebaceous glands were immunohistochemically examined. RESULTS: Immunohistochemistry results showed that there is a strong ghrelin immunoreactivity in the hair follicles and sebaceous glands in sections of human skin. The mean serum ghrelin levels (27.58 ・} 15.44 pg/mL) in patients with acne vulgaris was significantly lower than those of controls (35.62・}20.46 pg/mL). CONCLUSIONS: Ghrelin produced in hair follicles and sebaceous glands of the skin might participate in the pathogenesis of acne vulgaris and also acne vulgaris in humans might be associated with decreased serum ghrelin.