Suk-Jeong Kim

Consumption of policosanol enhances HDL functionality via CETP inhibition and reduces blood pressure and visceral fat in young and middle-aged subjects

It is well-known that policosanol can improve serum lipid profiles, although the physiological mechanism is still unknown. Here, we investigated functional and structural changes in lipoproteins after consumption of policosanol. To investigate the physiological effect of policosanol, we analyzed serum parameters in young non-smoker (YN; n=7, 24.0±2.4 years), young smoker (YS; n=7, 26.3±1.5 years), and middle-aged subjects (MN; n=11, 52.5±9.8 years) who consumed policosanol daily (10 mg/day) for 8 weeks. After 8 weeks, systolic blood pressure was significantly lowered to 4% (7 mmHg, p=0.022) from initial levels in the YS and MN groups. Moisture content of facial skin increased up to 38 and 18% from initial levels in the YS and MN groups, respectively. Serum triglyceride (TG) levels decreased to 28 and 26% from initial levels in the YN and MN groups, respectively. The percentage of high-density lipoprotein-cholesterol (HDL-C) in total cholesterol was elevated in all subjects (YN, 36%; YS, 35%; MN, 8%) after 8 weeks of policosanol consumption. All groups showed a reduction in serum glucose and uric acid levels. Serum cholesteryl ester transfer protein (CETP) activity was significantly diminished up to 21 and 32% from initial levels in the YN and MN groups, respectively. After 8 weeks, oxidation of the low-density lipoprotein fraction was markedly reduced accompanied by decreased apolipoprotein B (apoB) fragmentation. In the HDL fraction, paraoxonase activity was elevated by 17% along with elevation of apoA-I and cholesterol contents. Electron microscopy revealed that the size and number of HDL particles increased after 8 weeks, and the YS group showed a 2-fold increase in particle size. Daily consumption of policosanol for 8 weeks resulted in lowered blood pressure, reduced serum TG level and CETP activity, and elevated HDL-C contents. These functional enhancements of HDL can prevent and/or attenuate aging-related diseases, hypertension, diabetes and coronary heart disease.

Cadmium exposure exacerbates severe hyperlipidemia and fatty liver changes in zebrafish via impairment of high-density lipoproteins functionality

Cadmium (Cd) is a heavy metal with several toxicities that have destructive effect on most organ systems. However, its toxic effects on human lipoproteins are largely remained unknown especially in hyperlipidemic zebrafish model. Treatment of human high-density lipoprotein (HDL) with cadmium chloride (CdCl2, final 12 and 24μM) caused spontaneous formation of multimeric apoA-I as well as increased production of glycated extent products. Cd-HDL3 accelerated uptake of oxidized LDL (oxLDL) into macrophages and induced severe senescence in human dermal fibroblast (HDF) cells. Microinjection of Cd-HDL3 into zebrafish embryos resulted in acute embryonic toxicity with high mortality. Exposure of zebrafish embryos to water containing CdCl2 (final 12 and 24μM) caused early embryonic death along with increased production of oxidized products and impairment of skeletal development. Consumption of CdCl2 (12 and 24μM) by zebrafish for 4weeks resulted in severe elevation of plasma total cholesterol (TC) and triglyceride (TG) levels as well as cholesteryl ester (CE) transfer activity. Furthermore, consumption of CdCl2 resulted in acceleration of fatty liver changes and increased production of reactive oxygen species (ROS). In conclusion, CdCl2 caused structural modification of HDL3 and impaired the beneficial functions of HDL3, including anti-oxidation, anti-atherosclerosis, and anti-senescence effects. Consumption of CdCl2 also resulted in exacerbated hyperlipidemia and fatty liver changes in zebrafish via enhancement of cholesteryl ester transfer protein (CETP) activity.

Correlation among lipid parameters, pulse wave velocity and central blood pressure in young Korean population

ABSTRACT Background: Central blood pressure is closely related to the important cardiovascular intermediate end points, such as vascular hypertrophy and extent of carotid atherosclerosis. Therefore it is prudent to study correlation among central aortic blood pressure, body composition, lipid profiles, and pulse wave velocity in population-based study. Consequently, we investigate the correlation between central aortic blood pressure and other risk parameters of hypertension such as body composition and lipid profile. Methods: We recruited 20 young participants diagnosed with hypertension as well as 30 without hypertension. The study used an X-SCAN PLUS 950 machine for measurement of overall body composition. Measurements of central blood pressure and carotid–femoral pulse wave velocity were carried out using SphygmoCor XCEL. Results: The hypertensive participants had significantly higher total weight without fat, body moisture mass, muscle mass, body mass index, basal metabolic rate, intracellular and extracellular water contents, protein and mineral contents along with brachial and central aortic blood pressures. In both hypertensive and non-hypertensive participants, central aortic diastolic blood pressure were significantly related to the lipid parameters. Conclusion: Overall, the correlations between central blood pressure, pulse wave velocity, and lipid profile in hypertensive and non-hypertensive participants were substantial.

Methionine sulfoxide reductase B1 deficiency does not increase high-fat diet-induced insulin resistance in mice

Abstract Methionine-S-sulfoxide reductase (MsrA) protects against high-fat diet-induced insulin resistance due to its antioxidant effects. To determine whether its counterpart, methionine-R-sulfoxide reductase (MsrB) has similar effects, we compared MsrB1 knockout and wild-type mice using a hyperinsulinemic-euglycemic clamp technique. High-fat feeding for eight weeks increased body weights, fat masses, and plasma levels of glucose, insulin, and triglycerides to similar extents in wild-type and MsrB1 knockout mice. Intraperitoneal glucose tolerance test showed no difference in blood glucose levels between the two genotypes after eight weeks on the high-fat diet. The hyperglycemic-euglycemic clamp study showed that glucose infusion rates and whole body glucose uptakes were decreased to similar extents by the high-fat diet in both wild-type and MsrB1 knockout mice. Hepatic glucose production and glucose uptake of skeletal muscle were unaffected by MsrB1 deficiency. The high-fat diet-induced oxidative stress in skeletal muscle and liver was not aggravated in MsrB1-deficient mice. Interestingly, whereas MsrB1 deficiency reduced JNK protein levels to a great extent in skeletal muscle and liver, it markedly elevated phosphorylation of JNK, suggesting the involvement of MsrB1 in JNK protein activation. However, this JNK phosphorylation based on a p-JNK/JNK level did not positively correlate with insulin resistance in MsrB1-deficient mice. Taken together, our results show that, in contrast to MsrA deficiency, MsrB1 deficiency does not increase high-fat diet-induced insulin resistance in mice.

Consumption of Cuban Policosanol Improves Blood Pressure and Lipid Profile via Enhancement of HDL Functionality in Healthy Women Subjects: Randomized, Double-Blinded, and Placebo-Controlled Study

Policosanol has been reported to improve blood pressure, lipid profile, and HDL functionality via inhibition of cholesteryl ester transfer protein (CETP) both in vitro and in vivo in zebrafish and human models. However, there are limited reports and randomized, double-blinded trials on policosanol that could advocate the blood pressure-lowering effect in prehypertensive participants. Therefore, we performed in vitro, in vivo, and ex vivo experiments to provide more substantial and concrete data on the blood pressure-lowering effect of policosanol. Consumption of policosanol for 8 weeks enhanced plasma antioxidant activity. In the policosanol group, plasma total cholesterol (TC) and triglyceride (TG) levels were reduced up to 20% and 14%, respectively, and HDL-C level was elevated up to 1.3-fold compared to that at week 0. TG/HDL-C and cholesteryl ester transfer protein (CETP) activities were reduced up to 36% and 20%, respectively. Uptake of oxidized LDL in macrophages was reduced as oxidized species levels were reduced, and HDL2-associated paraoxonase activities were enhanced by 60% compared to those at week 0. Encapsulation of policosanol into reconstituted HDL (PCO-rHDL) enhanced cholesterol efflux activity and insulin secretion capacity. In conclusion, consumption of policosanol for 8 weeks in healthy female subjects resulted in lowered blood pressure and CETP activity via elevation of HDL/apoA-I contents and enhancement of HDL functionalities, including cholesterol efflux and insulin secretion. These functional enhancements of HDL can contribute to the prevention of aging-related diseases, hypertension, and stroke.

Long-Term Consumption of Cuban Policosanol Lowers Central and Brachial Blood Pressure and Improves Lipid Profile With Enhancement of Lipoprotein Properties in Healthy Korean Participants

Metabolic syndrome is closely associated with higher risk of hypertension, cardiovascular disease (CVD), diabetes and stroke. The aim of the present study was to investigate the long-term effects of policosanol supplementation on blood pressure (BP) and the lipid profile in healthy Korean participants with pre-hypertension (systolic 120–139 mmHg, diastolic 85–89 mmHg). This randomized, double-blinded, and placebo-controlled trial included 84 healthy participants who were randomly assigned to three groups receiving 10 mg of policosanol, 20 mg of policosanol, or placebo for 24 weeks. The BP, lipid profile, and anthropometric factors were measured pre- and post-intervention and then compared. Based on an average of three measurements of brachial BP, the policosanol 20 mg group showed the most significant reduction in average systolic BP (SBP) from 138 ± 12 mmHg at week 0 to 126 ± 13 mmHg at week 24 (p < 0.0001). The policosanol 20 mg group also showed significant reductions in aortic SBP and DBP up to 9% (p = 0.00057) and 8% (p = 0.004), respectively compared with week 0. Additionally, blood renin and aldosterone levels were significantly reduced in the policosanol 20 mg group up to 63% (p < 0.01) and 42% (p < 0.05), respectively, at week 24. For the blood lipid profile, the policosanol 10 mg and 20 mg groups showed significant reductions in total cholesterol (TC) of around 8% (p = 0.029) and 13% (p = 0.0004), respectively, at week 24 compared with week 0. Serum HDL-C level significantly increased up to 16% and 12% in the policosanol 10 mg (p = 0.002) and 20 mg (p = 0.035) group, respectively. The study results suggest that long-term policosanol consumption simultaneously reduces peripheral BP as well as aortic BP accompanied by elevation of HDL-C and % HDL-C in TC in a dose-dependent manner.

High Consumption of Iron Exacerbates Hyperlipidemia, Atherosclerosis, and Female Sterility in Zebrafish via Acceleration of Glycation and Degradation of Serum Lipoproteins.

Elevated serum iron level is linked with an increased risk of diabetes and atherosclerosis. However, the pathological mechanism by which iron affects serum lipoprotein levels is unknown. To elucidate the mechanism, a high dose of ferrous ion was applied (final 60 µM, 120 µM) to human serum lipoproteins, macrophages, and human dermal fibroblast (HDF) cells. Iron-treated lipoproteins showed loss of antioxidant ability along with protein degradation and multimerization, especially co-treatment with fructose (final 10 mM). In the presence of fructose, HDF cells showed 3.5-fold more severe cellular senescence, as compared to the control, dependent on the dosage of fructose. In macrophages, phagocytosis of acetylated low-density lipoprotein (acLDL) was more accelerated by ferrous ion, occurring at a rate that was up to 1.8-fold higher, than acLDL alone. After 24 weeks supplementation with 0.05% and 0.1% ferrous ion in the diet (wt/wt), serum total cholesterol (TC) level was elevated 3.7- and 2.1-fold, respectively, under normal diet (ND). Serum triglyceride (TG) was elevated 1.4- and 1.7-fold, respectively, under ND upon 0.05% and 0.1% ferrous ion supplementation. Serum glucose level was elevated 2.4- and 1.2-fold under ND and high cholesterol diet (HCD), respectively. However, body weight was decreased by the Fe2+ consumption. Iron consumption caused severe reduction of embryo laying and reproduction ability, especially in female zebrafish via impairment of follicular development. In conclusion, ferrous ion treatment caused more pro-atherogenic, and pro-senescence processes in human macrophages and dermal cells. High consumption of iron exacerbated hyperlipidemia and hyperglycemia as well as induced fatty liver changes and sterility along with reduction of female fertility.

Nutritional regulation of renal lipogenic factor expression in mice: comparison to regulation in the liver and skeletal muscle

Regulation of lipogenesis by pathophysiological factors in the liver and skeletal muscle is well understood; however, regulation in the kidney is still unclear. To elucidate nutritional regulation of lipogenic factors in the kidney, we measured the renal expression of lipogenic transcriptional factors and enzymes during fasting and refeeding in chow-fed and high-fat-fed mice. We also examined the regulatory effect of the liver X receptor (LXR) on the expression of lipogenic factors. The renal gene expression of sterol regulatory element-binding protein (SREBP)-1c and fatty acid synthase (FAS) was reduced by fasting for 48 h and restored by refeeding, whereas the mRNA levels of forkhead box O (FOXO)1/3 were increased by fasting and restored by refeeding. Accordingly, protein levels of SREBP-1, FAS, and phosphorylated FOXO1/3 were reduced by fasting and restored by refeeding. The patterns of lipogenic factors expression in the kidney were similar to those in the liver and skeletal muscle. However, this phasic regulation of renal lipogenic gene expression was blunted in diet-induced obese mice. LXR agonist TO901317 increased the lipogenic gene expression and the protein levels of SREBP-1 precursor and FAS but not nuclear SREBP-1. Moreover, increases in insulin-induced gene mRNA and nuclear carbohydrate-responsive element binding protein (ChREBP) levels were observed in the TO901317-treated mice. These results suggest that the kidney shows flexible suppression and restoration of lipogenic factors following fasting and refeeding in lean mice, but this is blunted in obese mice. LXR is involved in the renal expression of lipogenic enzymes, and ChREBP may mediate the response.

The Ability of Different Ketohexoses to Alter Apo-A-I Structure and Function In Vitro and to Induce Hepatosteatosis, Oxidative Stress, and Impaired Plasma Lipid Profile in Hyperlipidemic Zebrafish

In the current study, we have tested the nonenzymatic glycation activities of ketohexoses, such as tagatose and psicose. Although tagatose-treated apoA-I (t-A-I) and psicose-treated apoA-I (p-A-I) exerted more inhibitory activity you cupric ion-mediated low-density lipoprotein (LDL) oxidation and oxidized LDL (oxLDL) phagocytosis into macrophage than fructose-treated apoA-I (f-A-I). In the lipid-free state, t-A-I and f-A-I showed more multimerized band without crosslinking. Since t-A-I lost its phospholipid binding ability, the rHDL formation was not as successful as f-A-I. However, injecting t-A-I showed more antioxidant activities in zebrafish embryo under the presence of oxLDL. Three weeks of consumption of fructose (50% of wt in Tetrabit/4% cholesterol) showed a 14% elevation of serum triacylglycerol (TG), while tagatose-administered group showed 30% reduction in serum TG compared to high cholesterol control. Fructose-fed group showed the biggest area of Oil Red O staining with the intensity as strong as the HCD control. However, tagatose-consumed group showed much lesser Oil Red O-stained area with the reduction of lipid accumulation. In conclusion, although tagatose treatment caused modification of apoA-I, the functional loss was not as much severe as the fructose treatment in macrophage cell model, zebrafish embryo, and hypercholesterolemic zebrafish model.

Blood Pressure Lowering Effect of Cuban Policosanol is Accompanied by Improvement of Hepatic Inflammation, Lipoprotein Profile, and HDL Quality in Spontaneously Hypertensive Rats

We investigated the antihypertensive effect of policosanol on spontaneously hypertensive rats (SHR). For this, we analyzed blood pressure, blood lipid, and lipoprotein properties in male SHR after consumption of Cuban policosanol (PCO). The experimental groups were as follows: normotensive Wistar Kyoto (WKY) control, SHR group fed normal diet (ND), SHR group fed 20 mg of PCO, SHR group fed 100 mg of PCO, and SHR group fed 200 mg of PCO per kg of body weight. After eight weeks, the SHR control group showed gradual increases up to 22% in systolic blood pressure (SBP) and 17.6% in the diastolic blood pressure (DBP) compared with values at week 0. However, policosanol consumption had a dose-dependent reduction effect on SBP and also reduced DBP up to 16% in a dose-dependent manner. Heart rate (HR) bpm increased by six percent in the SHR control, whereas the 20 mg, 100 mg, and 200 mg of policosanol groups showed a reduction of 36%, 28%, and 34% respectively. Although serum total cholesterol (TC) level of SHR was not affected by policosanol consumption (70–80 mg/dL), serum triglyceride (TG) level significantly decreased in the SHR + 200 mg of PCO group. Serum high-density lipoprotein cholesterol (HDL-C) level was also significantly elevated by policosanol consumption. The % HDL-C/TC ratio was elevated in the policosanol group up to 67–70%, whereas the SHR control group showed a ratio of 58%. Serum cholesteryl ester transfer protein (CETP) activity was reduced by policosanol in a dose-dependent manner. Although the serum glutamate oxaloacetate transaminase (GOT)/ glutamate pyruvate transaminase (GPT) were similar across all groups, policosanol consumption caused reduction of reactive oxygen species (ROS) levels in hepatic tissue. The SHR control group showed a 2.1-fold higher serum C-reactive protein (CRP) level than the WKY group, whereas the CRP level decreased in the SHR + 200 mg of PCO group (up to 45%) than SHR control group. Aldosterone level was reduced in the policosanol group (up to 34%) in a dose-dependent manner compared to the control. In conclusion, eight weeks of policosanol consumption in SHR resulted in remarkable reduction of blood pressure, serum aldosterone, and serum TG levels along with the elevation of HDL-C and improvement of hepatic inflammation.