Objective: To explore the correlation of serum lipids levels of Alzheimer's disease (AD) patients with sex, age and apolipoprotein E (Apo E) gene polymorphism. Methods: The retrospective study method was used, and 407 AD patients (142 males and 265 females, aged 52-91 years) were selected from Beijing Tiantan Hospital from January 2015 to August 2021 as the research target, and 894 healthy persons (339 males and 555 females, aged 52-94 years) who did body examination were selected as the control group. The AD patients were divided into four age groups according to the age interval of 10 years, including 85 aged 50-59 years, 163 aged 60-69 years, 119 aged 70-79 years, and 40 aged more than 80 years. The serum lipids levels were detected by biochemical analyzer, including triglycerides (TG), cholesterol (CHO), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoproteinA1(Apo A1) and apolipoprotein B (Apo B). ApoE gene polymorphism were detected by PCR fluorescent probe method. Mann-Whitney U test and Kruskal-Wallis H test were used to compare the serum lipids levels in each group. Results: The levels of serum CHO and LDL-C were 3.30(1.41,4.82) mmol/L and 1.76(1.39,2.78) mmol/L in AD patients, and 4.84(4.24, 5.56) mmol/L and 2.91(2.36, 3.57) mmol/L in control group, and the levels of serum CHO and LDL-C of AD patients were significantly lower than control group (Z=-15.172,Z=-14.583 , P<0.001, P<0.001). The levels of serum HDL-C and Apo B were 1.84(1.30, 3.88) mmol/L and 1.17(0.85, 1.57) g/L in AD patients, and 1.39(1.18, 1.64) mmol/L and 0.93(0.81, 1.09) g/L in control group, and the levels of serum HDL-C and Apo-B of AD patients were significantly higher than control group (Z=-12.249 , Z=-9.706 , P<0.001, P<0.001). There was no significant difference in TG and Apo A1 between 2 groups (Z=-1.577 , Z=-0.408 , P=0.115, P=0.683). The levels of TG, CHO, LDL-C in female AD patients were significantly higher than male patients (Z=-2.737 , Z=-3.963 , Z=-4.417, P=0.006, P<0.001, P<0.001). There were significant differences in TG, CHO, HDL-C, LDL-C, Apo A1 and Apo B among AD patients of all age groups (Z=11.263 , Z=10.060 , Z=40.246 , Z=10.451 , Z=24.315 , Z=19.922 , P=0.010 , P=0.018 , P<0.001 , P=0.015 , P<0.001 , P<0.001). The serum CHO and LDL-C levels were positively correlated with age (r_s=0.160, r_s=0.174, P=0.001, P<0.001), and HDL-C, Apo A1 and Apo B levels were negatively correlated with age (r_s=-0.312, r_s=-0.272, r_s=-0.146, P<0.001, P<0.001, P=0.003), and there was no correlation between TG level and age in AD patients (r_s=0.086, P=0.082). There were 3 cases (3.33%) of E2, 43 cases of E3 (47.78%) and 44 cases of E4 (48.89%) in AD patients, and 22 cases (12.72%) of E2, 117 cases of E3 (67.63%) and 34 cases of E4 (19.65%) in control group. There was significant difference in Apo E genotype distribution between AD patients and control group (χ²=26.381 , P<0.001). Apo E4 was the most common genotype in AD patients, and the proportion was 48.89%. Except for Apo A1(Z=7.821 , P=0.020), there was no significant difference in TG, CHO, HDL-C, LDL-C and Apo B levels among all patients with different genotypes (Z=3.732 , Z=1.677 , Z=1.455 , Z=1.619 , Z=2.202 , P=0.155, P=0.432, P=0.483, P=0.445, P=0.333). Conclusion: The levels of CHO and LDL-C decreased while the levels of HDL-C and Apo B increased in AD patients. The dyslipidemia in AD patients might be correlated with age, but not sex and Apo E genotypes.
Aged ; Aged, 80 and over ; Alzheimer Disease/genetics* ; Apolipoproteins E/genetics* ; Cholesterol, HDL/blood* ; Female ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; Retrospective Studies ; Triglycerides/blood*

OBJECTIVE: To evaluate the effects of 12 weeks high intensity interval training(HIIT) on serum lipids profile in patients with dyslipidemia of different apolipoprotein E(ApoE) genotypes. METHODS: Eighty-eight patients with dyslipidemia were screened by fasting blood lipid as subjects. Apolipoprotein E genotypes were detected in oral mucosa of subjects. Serum lipids before and after 12 weeks high intensity interval training were measured to analysis the effect of high intensity interval training on serum lipids. RESULTS: Five genotypes were detected in 88 cases of dyslipidemia. The distributions were ApoE3/3＞ApoE3/4＞ApoE2/3＞ApoE2/2＞ApoE2/4,and allele ε3＞ε2=ε4. Before exercise intervention, the level of total cholesterol in patients with ε4 allele was significant higher than those in patients with ε2 and ε3 (P＜0.01), low density lipoprotein cholesterol in patients with ε4 was significant higher than that of patients with ε2 (P＜0.05), and the other indexes had no significant difference among the groups (P＞ 0.05). After 12 weeks high intensity interval training, the levels of total cholesterol, triglyceride and low density lipoprotein cholesterol were decreased significantly ,while the level of high density lipoprotein cholesterol was increased in those patients with ε3 genotype. For those individuals with ε4 genotype , their serum levels of total cholesterol and low density lipoprotein cholesterol were reduced after 12 weeks high intensity interval training , but there was no changes in serum levels of triglyceride and high density lipoprotein cholesterol. For those individuals with ε2 genotype, there was no significant improvement in serum lipids after 12 weeks high intensity interval training interventions. CONCLUSION The polymorphisms of apolipoprotein E gene resulted in different effects of exercise interventions on serum lipids of dyslipidemia. Twelve weeks high intensity interval training can be used as an intervention method to regulate serum lipids of dyslipidemia with ε3 and ε4 alleles.
Apolipoproteins E ; genetics ; Dyslipidemias ; genetics ; therapy ; Genotype ; High-Intensity Interval Training ; Humans ; Lipids ; blood

BACKGROUND: Metabolic syndrome (MetS) is a complex and multifactorial disorder characterized by insulin resistance, dyslipidaemia, hyperglycemia, abdominal obesity, and elevated blood pressure. The apolipoprotein A5 (APOA5) gene variants have been reported to correlate with two major components of MetS, including low levels of high density lipoprotein cholesterol (HDL-C) and high levels of triglyceride. In the present study, we explored the associations between five single nucleotide polymorphisms (SNPs) of APOA5 gene and the MetS risk. METHODS: In a case-control design, 120 Iranian children and adolescents with/without MetS were genotyped by polymerase chain reaction-sequencing for these SNPs. Then, we investigated the association of SNPs, individually or in haplotype constructs, with MetS risk. RESULTS: The rs34089864 variant and H1 haplotype (harboring the two major alleles of rs619054 and rs34089864) were associated with HDL-C levels. However, there was no significant association between different haplotypes/individual SNPs and MetS risk. CONCLUSION: These results presented no association of APOA5 3’UTR SNPs with MetS. Further studies, including other polymorphisms, are required to investigate the involvement of APOA5 gene in the genetic susceptibility to MetS in the pediatric age group.
Adolescent ; Alleles ; Apolipoproteins ; Blood Pressure ; Case-Control Studies ; Child ; Cholesterol, HDL ; Genetic Predisposition to Disease ; Haplotypes ; Humans ; Hyperglycemia ; Insulin Resistance ; Obesity, Abdominal ; Polymorphism, Single Nucleotide ; Triglycerides

BACKGROUND/OBJECTIVES: In this randomized, placebo-controlled, double-blind study, we evaluated the antihypertensive effects of enzymatic hydrolysate from Styela clava flesh tissue in patients with type 2 diabetes mellitus (T2DM) and hypertension. SUBJECTS/METHODS: S. clava flesh tissue hydrolysate (SFTH) (n = 34) and placebo (n = 22) were randomly allocated to the study subjects. Each subject ingested two test capsules (500 mg) containing powdered SFTH (SFTH group) or placebo capsules (placebo group) during four weeks. RESULTS: In the SFTH group, systolic and diastolic blood pressure decreased significantly 4 weeks after ingestion by 9.9 mmHg (P < 0.01) and 7.8 mmHg (P < 0.01), respectively. In addition, the SFTH group exhibited a significant decrease in hemoglobin A1c with a tendency toward improvement in homeostasis model assessment of insulin resistance, triglyceride, apolipoprotein B and plasma insulin levels after 4 weeks. No adverse effects were observed in other indexes, including biochemical and hematological parameters in both groups. CONCLUSION: The results of our study suggested that SFTH exerts a regulatory, antihypertensive effect in patients with T2DM and hypertension.
Antihypertensive Agents ; Apolipoproteins ; Aquatic Organisms ; Blood Pressure ; Capsules ; Diabetes Mellitus, Type 2 ; Double-Blind Method ; Eating ; Homeostasis ; Humans ; Hypertension* ; Insulin ; Insulin Resistance ; Plasma ; Protein Hydrolysates ; Triglycerides

BACKGROUND: Tacrolimus (Tac) can cause impaired insulin release and dyslipidemia, and may affect the development of post-transplant diabetes mellitus. However, these effects on insulin sensitivity and lipid profile have not been compared in renal transplant recipients receiving traditional twice-daily tacrolimus (TacBID) or cyclosporine and those receiving once-daily prolonged release formulation of tacrolimus (TacOD). METHODS: We conducted an observational prospective study of 15 stable non-diabetic renal transplant recipients to observe the changes in insulin sensitivity and lipid profiles for 1 year at a tertiary hospital. We evaluated the levels of hemoglobin A1c, total cholesterol, high density lipoprotein, low density lipoprotein, triglycerides, apolipoprotein A1, apolipoprotein B, serum creatinine, fasting plasma glucose, fasting insulin, homeostatic model assessment of β-cell (HOMA-β) and HOMA-insulin resistance index at baseline and at 2 and 4 months. To analyze differences in parameters, we conducted a Wilcoxon rank sum test and general linear model (GLM)-repeated measures analysis of variance (ANOVA) in both groups (cyclosporine to TacOD conversion group/TacBID to TacOD conversion group). RESULTS: At baseline, parameters did not differ between groups. GLM-repeated measures ANOVA revealed no change in insulin sensitivity or lipid profile after conversion at baseline or at 2 and 4 months. There were no complications after conversion from standard TacBID or cyclosporine to TacOD. CONCLUSIONS: There was no change in insulin sensitivity or lipid profile in renal transplant recipients. Any conversion from TacBID to TacOD should be performed in a controlled manner under close surveillance.
Apolipoprotein A-I ; Apolipoproteins ; Blood Glucose ; Cholesterol ; Creatinine ; Cyclosporine* ; Diabetes Mellitus ; Dyslipidemias ; Fasting ; Insulin Resistance* ; Insulin* ; Kidney Transplantation ; Linear Models ; Lipoproteins ; Prospective Studies ; Tacrolimus* ; Tertiary Care Centers ; Transplant Recipients* ; Triglycerides

This study aimed to investigate the association of Apolipoprotein B (ApoB) with the risk of diabetes in Koreans. Korean men (n = 790, 40-79 years) who had been never diagnosed for diabetes before participating were enrolled. Subjects were categorized into normal fasting glucose (NFG, n = 519), impaired fasting glucose (IFG, n = 188) and newly-onset diabetes (n = 83) according to fasting glucose levels. Age was not significantly different among the subgroups. Mean values of BMI, waist circumference, Blood pressure(BP), triglyceride, non-HDL cholesterol were significantly higher in IFG or newly-onset diabetic subjects compared to NFG subjects. The levels of glucose, insulin, free fatty acid, insulin resistance and ApoB were highest in diabetic patients and lowest in NFG subjects. According to ApoB level, subjects were divided into two groups (high-ApoB group: ≥ 87.0 mg/dL vs. low-ApoB group: < 87.0 mg/dL). The risk of diabetes was higher in the high-ApoB group than the low-ApoB group [OR₀: 2.392, (95% CI: 1.470-3.893), P₀< 0.001]. This association was maintained after adjusted for age and BMI [OR₁: 2.228, (95% CI: 1.362-3.646), P₁ = 0.001] and further adjustment for blood pressure, triglyceride, HDL-cholesterol, LDL-cholesterol, non-HDL-cholesterol, ApoA1 and adiponectin [OR₂: 1.984, (95% CI: 1.001-4.064), P₂ = 0.049]. The association was much greater in subjects with metabolic syndrome (MetS) [OR₁: 2.805 (95% CI: 1.137-5.737), P₁ = 0.005] than in those without [OR₁: 1.917 (95% CI: 0.989-3.718), P₁ = 0.054]. After 3-month, further investigation was randomly performed in subjects with NFG or IFG who agreed to reinvestigation. Multiple stepwise regression analysis revealed that net change of ApoB levels was a main contributor to the net change of glucose levels (standardized b-coefficient: 0.315, p = 0.002). In conclusion, ApoB levels are closely associated with the increased risk of diabetes in Korean men.
Adiponectin ; Apolipoproteins B ; Apolipoproteins* ; Blood Pressure ; Cholesterol ; Fasting ; Glucose ; Humans ; Insulin ; Insulin Resistance ; Male ; Triglycerides ; Waist Circumference

Fibroblast growth factor 21 (FGF21) is a metabolic hormone with pleiotropic effects on energy metabolism and insulin sensitivity. Besides its antiobese and antidiabetic activity, FGF21 also possesses the protective effects against atherosclerosis. Circulating levels of FGF21 are elevated in patients with atherosclerosis, macrovascular and microvascular complications of diabetes, possibly due to a compensatory upregulation. In apolipoprotein E-deficient mice, formation of atherosclerotic plaques is exacerbated by genetic depletion of FGF21, but is attenuated upon replenishment with recombinant FGF21. However, the blood vessel is not the direct target of FGF21, and the antiatherosclerotic activity of FGF21 is attributed to its actions in adipose tissues and liver. In adipocytes, FGF21 promotes secretion of adiponectin, which in turn acts directly on blood vessels to reduce endothelial dysfunction, inhibit proliferation of smooth muscle cells and block conversion of macrophages to foam cells. Furthermore, FGF21 suppresses cholesterol biosynthesis and attenuates hypercholesterolemia by inhibiting the transcription factor sterol regulatory element-binding protein-2 in hepatocytes. The effects of FGF21 on elevation of adiponectin and reduction of hypercholesterolemia are also observed in a phase-1b clinical trial in patients with obesity and diabetes. Therefore, FGF21 exerts its protection against atherosclerosis by fine-tuning the interorgan crosstalk between liver, brain, adipose tissue, and blood vessels.
Adipocytes ; Adiponectin ; Adipose Tissue ; Animals ; Apolipoproteins ; Atherosclerosis* ; Blood Vessels ; Brain ; Cholesterol ; Energy Metabolism ; Fibroblast Growth Factors* ; Fibroblasts* ; Foam Cells ; Hepatocytes ; Humans ; Hypercholesterolemia ; Insulin Resistance ; Liver ; Macrophages ; Mice ; Myocytes, Smooth Muscle ; Obesity ; Plaque, Atherosclerotic ; Transcription Factors ; Up-Regulation ; Vascular Diseases

OBJECTIVETo investigate the effects of the DPP4 inhibitor sitagliptin on the expressions of early growth response-1 (Egr-1) and fibronectin in the kidney of ApoE gene knockout mice.

METHODSEight-week-old male ApoE gene knockout mice were randomly divided into sitagliptin + apoE(-/-) group and apoE(-/-) group (n=6), with 6 C57BL mice as the normal control group. After feeding with high-fat diet and drug treatment for 16 weeks, the mice underwent intraperitoneal glucose tolerance test (IPGTT) and were measured for 24-h urinary albumin using ELISA. All the mice were then sacrificed to examine the changes of blood lipid profile and for detection of Egr-1 and fibronectin mRNA and proteins in the renal tissue using real-time PCR and Western blotting.

RESULTSThe mice in both apoE(-/-) group and sitagliptin+apoE(-/-) group all showed prominently increased blood lipids as compared with the control group (P<0.05) without significant differences between the two apoE(-/-) groups. The level of HDL was significantly higher in sitagliptin +apoE(-/-) group than in apoE(-/-) group (P<0.001) and control group (P<0.001). IPGTT showed no significant differences in the levels of blood glucose among the 3 groups. The excretion of urinary albumin was increased in apoE(-/-) group compared with the control group (P<0.01), but was significantly lower in sitagliptin+ apoE(-/-) group than in apoE(-/-) group (P<0.01). Real-time PCR and Western blotting showed significantly decreased mRNA and protein expressions of renal cortical Egr-1 and fibronectin in sitagliptin+apoE(-/-) group compared with apoE(-/-) group.

CONCLUSIONSitagliptin can reduce the renal expression of fibronectin by regulating the expression of Egr-1 to achieve renal protection.

Animals ; Apolipoproteins E ; genetics ; Diet, High-Fat ; Dipeptidyl-Peptidase IV Inhibitors ; pharmacology ; Early Growth Response Protein 1 ; metabolism ; Fibronectins ; metabolism ; Gene Knockout Techniques ; Kidney ; metabolism ; Lipids ; blood ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Real-Time Polymerase Chain Reaction ; Sitagliptin Phosphate ; pharmacology

BACKGROUNDMenopausal hormone therapy (MHT) has been proven to have beneficial effects on several components of metabolic syndrome. However, the effects vary according to different regimens, dosages, and duration of MHT. The aim of the study was to evaluate the effect of standard-dose 0.625 mg conjugated equine estrogen (CEE) and half-dose 0.3 mg CEE daily with different progestogens in a continuous sequential regimen on postmenopausal metabolic parameters in generally healthy postmenopausal women.

METHODSA prospective, open-label, randomized controlled clinical trial was conducted between February 2014 and December 2015. Totally 123 Chinese postmenopausal women with climacteric symptoms were included in this study and were randomly assigned to three groups: Group A received CEE 0.3 mg/micronized progesterone (MP) 100 mg daily; Group B received CEE 0.625 mg/MP 100 mg daily; and Group C received CEE 0.625 mg/dydrogesterone 10 mg daily. Drugs were given in a continuous sequential pattern. The duration of treatment was 12 months. Clinical, anthropometrical, and metabolic variables were measured. Data were analyzed according to intention-to-treat analysis, using Student's t-test and analysis of variance.

RESULTSA total of 107 participants completed the 12-month follow-up and were included in the data analysis. At 12 months of treatment, high-density lipoprotein cholesterol and apolipoprotein A significantly increased, and low-density lipoprotein cholesterol, fasting glucose, and glycosylated hemoglobin significantly decreased in Groups B and C, compared with baseline (all P < 0.05). Among the three groups, only Group C showed significantly increased triglycerides compared with baseline (1.61 ± 0.80 mmol/L vs. 1.21 ± 0.52 mmol/L, P = 0.026). Each group showed a neutral effect on total cholesterol, lipoprotein A, apolipoprotein B, and fasting insulin levels. No cardiovascular and venous thromboembolic events occurred in the three groups.

CONCLUSIONSAmong Chinese postmenopausal women, half-dose CEE was not sufficient to induce a favorable lipid and carbohydrate profile compared with standard-dose CEE. Adding natural MP may counterbalance the TG-increasing effect of CEE.

TRIAL REGISTRATIONClinicalTrials.gov, NCT01698164; https://clinicaltrials.gov/ct2/show/NCT01698164?term=NCT01698164&rank=1.

Apolipoproteins B ; blood ; Blood Pressure ; drug effects ; Body Composition ; drug effects ; Dydrogesterone ; administration & dosage ; therapeutic use ; Estrogens, Conjugated (USP) ; administration & dosage ; therapeutic use ; Female ; Humans ; Insulin ; blood ; Lipoprotein(a) ; blood ; Metabolic Syndrome ; blood ; drug therapy ; Middle Aged ; Postmenopause ; Progesterone ; administration & dosage ; therapeutic use ; Triglycerides ; blood

OBJECTIVETo study the effect of polydatin on the expression level of miR-214 and liver function in atherosclerotic mice.

METHODSForty male ApoE(-/-) mice were randomly allocated into 4 groups (n=10), namely the model group, low- and high-dose polydatin groups, and simvastin group, with 10 male C57BL/6J mice serving as the normal control group. Mouse models of atherosclerosis were established by feeding the ApoE(-/-) mice with a high-fat diet. After 12 weeks of treatment, blood levels of glucose, lipids, AST, and ALT and the contents of T-SOD and MDA in the liver tissue were detected. The pathologies of the liver were examined with HE staining, and miR-214 expression in the liver was detected using quantitative real-time PCR.

RESULTSCompared with the normal control mice, the mice in the model group showed significantly increased blood glucose, serum TC, TG, LDL-C, ALT, and AST levels, and MDA contents in the liver (P<0.01), with significantly decreased serum HDL-C level and SOD and miR-214 levels in liver (P<0.01). Polydatin treatment significantly ameliorated such changes in blood glucose, serum ALT, AST, TC, TG, LDL-C, and HDL-C levels, and MDA, SOD, and miR-214 contents in liver tissue (P<0.05).

CONCLUSIONs Polydatin can reduce blood glucose and lipid levels and protect the liver function in atherosclerotic mice possibly by up-regulating the expression of miR-214 and T-SOD and down-regulating MDA in the liver.

Animals ; Apolipoproteins E ; genetics ; Atherosclerosis ; drug therapy ; Blood Glucose ; analysis ; Diet, High-Fat ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Glucosides ; pharmacology ; Lipids ; blood ; Liver ; drug effects ; Male ; Malondialdehyde ; metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; MicroRNAs ; metabolism ; Stilbenes ; pharmacology ; Superoxide Dismutase ; metabolism