Increased Plasma Triglyceride Levels Research Articles

Telmisartan ameliorates adipoR1 and adipoR2 expression via PPAR-γ activation in the coronary artery and VSMCs

The effects of telmisartan on insulin-resistant properties and expression of adiponectin receptors (AdipoRs) were investigated. A diabetic rat model was established using a high-fat diet and streptozotocin (25mg/kg) and primary rat coronary vascular smooth muscle cells (VSMCs) were used to elucidate the underlying mechanisms. The diabetic rats were insulin-resistant and exhibited weight gain, elevated blood pressures, and increased plasma triglyceride levels. These manifestations were ameliorated by elmisartan treatment. Four-week telmisartan therapy increased plasma adiponectin and decreased TNF-α expression in the coronary artery. Moreover, telmisartan significantly decreased AdipoR1 and AdipoR2 expression. Using high glucose-treated rat coronary VSMCs, telmisartan and PPAR-γ agonist GW1929 prominently stimulated PPAR-γ and decreased TNF-α expression. Interestingly, telmisartan or GW1929 also prevented hyperglycemia-induced downregulation of AdipoR1 and AdipoR2 expression. Additionally, GW9662 (PPAR-γ antagonist) significantly decreased the effects of telmisartan on AdipoR1 and AdipoR2 expression. These results demonstrated that telmisartan effectively ameliorated coronary insulin resistance and inflammation in diabetic rats and upregulated AdipoR1/R2 expression via activation of PPAR-γ in the coronary artery and VSMCs.

Farnesoid X receptor antagonist exacerbates dyslipidemia in mice.

The effects of farnesoid X receptor (FXR) antagonists on plasma lipid profile in mice have not been investigated thus far. The aim of this study was to investigate the antidyslipidemic effects of an FXR antagonist in dyslipidemic mice, and to clarify the mechanisms underlying the lipid modulatory effect. Compound-T0 (1-100 mg/kg) was orally administered to C57BL/6J mice fed a Western-type diet or low-density lipoprotein receptor knockout (LDLR-/-) mice fed a Western-type diet for a week, and plasma lipid levels were investigated. Effects on lipid clearance, hepatic triglyceride secretion after Triton WR-1339 challenge, and intestinal lipid absorption were investigated after multiple dosing. Compound-T0 significantly increased plasma level of non-high-density lipoprotein cholesterol in both C57BL/6 and LDLR-/- mice; in addition, it significantly increased plasma triglyceride level in LDLR-/- mice. Compound-T0 failed to enhance the clearance of 3,3'-dioctadecylindocarbocyanine (DiI)-labeled LDL in C57BL/6J mice. Although compound-T0 did not affect triglyceride clearance and hepatic triglyceride secretion, it significantly increased intestinal [3H]cholesterol absorption in LDLR-/- mice. It was found that the FXR antagonist, compound-T0 exacerbated dyslipidemia in mice because it enhanced intestinal lipid absorption via acceleration of bile acid excretion.

Effects of Low-Dose Developmental Bisphenol A Exposure on Metabolic Parameters and Gene Expression in Male and Female Fischer 344 Rat Offspring.

Background:Bisphenol A (BPA) is an endocrine-disrupting chemical that may contribute to development of obesity and metabolic disorders. Humans are constantly exposed to low concentrations of BPA, and studies support that the developmental period is particularly sensitive.Objectives:The aim was to investigate the effects of low-dose developmental BPA exposure on metabolic parameters in male and female Fischer 344 (F344) rat offspring.Methods:Pregnant F344 rats were exposed to BPA via their drinking water, corresponding to (BPA0.5; ) or (BPA50; ), from gestational day (GD) 3.5 until postnatal day (PND) 22, and controls were given vehicle (). Body weight (BW), adipose tissue, liver (weight, histology, and gene expression), heart weight, and lipid profile were investigated in the 5-wk-old offspring.Results:Males and females exhibited differential susceptibility to the different doses of BPA. Developmental BPA exposure increased plasma triglyceride levels ( compared with , females BPA50 ; compared with , males BPA0.5 ) in F344 rat offspring compared with controls. BPA exposure also increased adipocyte cell density by 122% in inguinal white adipose tissue (iWAT) of female offspring exposed to BPA0.5 compared with controls ( number of adipocytes/HPF compared with number of adipocytes/HPF; ) and by 123% in BPA0.5 females compared with BPA50 animals ( number of adipocytes/high power field (HPF) compared with number of adipocytes/HPF; ). In iWAT of male offspring, adipocyte cell density was increased by 129% in BPA50-exposed animals compared with BPA0.5-exposed animals ( number of adipocytes/HPF compared with number of adipocytes/HPF; ). Furthermore, the expression of genes involved in lipid and adipocyte homeostasis was significantly different between exposed animals and controls depending on the tissue, dose, and sex.Conclusions:Developmental exposure to of BPA, which is 8–10 times lower than the current preliminary EFSA (European Food Safety Authority) tolerable daily intake (TDI) of and is within the range of environmentally relevant levels, was associated with sex-specific differences in the expression of genes in adipose tissue plasma triglyceride levels in males and adipocyte cell density in females when F344 rat offspring of dams exposed to BPA at were compared with the offspring of unexposed controls. https://doi.org/10.1289/EHP505

ANGPTL8 requires ANGPTL3 to inhibit lipoprotein lipase and plasma triglyceride clearance

Angiopoietin-like (ANGPTL)3 and ANGPTL8 are secreted proteins and inhibitors of LPL-mediated plasma triglyceride (TG) clearance. It is unclear how these two ANGPTL proteins interact to regulate LPL activity. ANGPTL3 inhibits LPL activity and increases serum TG independent of ANGPTL8. These effects are reversed with an ANGPTL3 blocking antibody. Here, we show that ANGPTL8, although it possesses a functional inhibitory motif, is inactive by itself and requires ANGPTL3 expression to inhibit LPL and increase plasma TG. Using a mutated form of ANGPTL3 that lacks LPL inhibitory activity, we demonstrate that ANGPTL3 activity is not required for its ability to activate ANGPTL8. Moreover, coexpression of ANGPTL3 and ANGPTL8 leads to a far more efficacious increase in TG in mice than ANGPTL3 alone, suggesting the major inhibitory activity of this complex derives from ANGPTL8. An antibody to the C terminus of ANGPTL8 reversed LPL inhibition by ANGPTL8 in the presence of ANGPTL3. The antibody did not disrupt the ANGPTL8:ANGPTL3 complex, but came in close proximity to the LPL inhibitory motif in the N terminus of ANGPTL8. Collectively, these data show that ANGPTL8 has a functional LPL inhibitory motif, but only inhibits LPL and increases plasma TG levels in mice in the presence of ANGPTL3.

TMG-123, a novel glucokinase activator, exerts durable effects on hyperglycemia without increasing triglyceride in diabetic animal models.

Glucokinase (GK) plays a critical role for maintaining glucose homeostasis with regulating glucose uptake in liver and insulin secretion in pancreas. GK activators have been reported to decrease blood glucose levels in patients with type 2 diabetes mellitus. However, clinical development of GK activators has failed due to the loss of glucose-lowering effects and increased plasma triglyceride levels after chronic treatment. Here, we generated a novel GK activator, TMG-123, examined its in vitro and in vivo pharmacological characteristics, and evaluated its risks of aforementioned clinical issues. TMG-123 selectively activated GK enzyme activity without increasing Vmax. TMG-123 improved glucose tolerance without increasing plasma insulin levels in both insulin-deficient (Goto-Kakizaki rats) and insulin-resistant (db/db mice) models. The beneficial effect on glucose tolerance was greater than results observed with clinically available antidiabetic drugs such as metformin and glibenclamide in Zucker Diabetic Fatty rats. TMG-123 also improved glucose tolerance in combination with metformin. After 4 weeks of administration, TMG-123 reduced the Hemoglobin A1c levels without affecting liver and plasma triglyceride levels in Goto-Kakizaki rats and Diet-Induced Obesity mice. Moreover, TMG-123 sustained its effect on Hemoglobin A1c levels even after 24 weeks of administration without affecting triglycerides. Taken together, these data indicate that TMG-123 exerts glucose-lowering effects in both insulin-deficient and -resistant diabetes, and sustains reduced Hemoglobin A1c levels without affecting hepatic and plasma triglycerides even after chronic treatment. Therefore, TMG-123 is expected to be an antidiabetic drug that overcomes the concerns previously reported with other GK activators.

Quantitative proteomics analysis reveals perturbation of lipid metabolic pathways in the liver of Atlantic cod (Gadus morhua) treated with PCB 153

PCB 153 is one of the most abundant PCB congeners detected in biological samples. It is a persistent compound that is still present in the environment despite the ban on production and use of PCBs in the late 1970s. It has strong tendencies to bioaccumulate and biomagnify in biota, and studies have suggested that it is an endocrine and metabolic disruptor. In order to study mechanisms of toxicity, we exposed Atlantic cod (Gadus morhua) to various doses of PCB 153 (0, 0.5, 2 and 8mg/kg body weight) for two weeks and examined the effects on expression of liver proteins using label-free quantitative proteomics. Label-free liquid chromatography-mass spectrometry analysis of the liver proteome resulted in the quantification of 1272 proteins, of which 78 proteins were differentially regulated in the PCB 153-treated dose groups compared to the control group. Functional enrichment analysis showed that pathways significantly affected are related to lipid metabolism, cytoskeletal remodeling, cell cycle and cell adhesion. Importantly, the main effects appear to be on lipid metabolism, with up-regulation of enzymes in the de novo fatty acid synthesis pathway, consistent with previous transcriptomics results. Increased plasma triglyceride levels were also observed in the PCB 153 treated fish, in agreement with the induction of the lipogenic genes and proteins. The results suggest that PCB 153 perturbs lipid metabolism in the Atlantic cod liver. Elevated levels of lipogenic enzymes and plasma triglycerides further suggest increased synthesis of fatty acids and triglycerides.

Myelo peroxidase as an Indicator of Oxidative Stress in Metabolic Syndrome

Background: Increased myeloperoxidase (MPO) activity would be the link between the rise of the inflammatory response and oxidative stress (OS) in metabolic syndrome (MS). Objective: The aim of this study was to determine the enzymatic activity of MPO associated with OS in animals with MS and establish their relationship with probable cardiovascular injury. Methods: Male Wistar rats were divided into two groups: Group A, control (n=12) and Group B, induced MS (n=12). Metabolic syndrome was produced by 6-week administration of 10% fructose diluted in the drinking water. Insulin (mU/ml), glucose (mg/dl), lipid panel (mg/dl), HOMA (homeostatic model assessment), MPO (IU/ml) and superoxide dismutase (SOD) activity (U/ml) were measured. Light microscopy was used for the histological study of the heart and thoracic aorta. Results: Group B showed significantly increased levels of plasma glucose (176±17.3 mg/dl), insulin (29.5±4.52 mU/ml), HOMA (11±1.3), total cholesterol (133±9.6 mg/dl) and triglycerides (75±12.9 mg/dl) compared with Group A: plasma glucose (115±1.1 mg/dl), insulin (4±0.82 mU/ml), HOMA (3±0.38), total cholesterol (69.7±1.6 mg/dl) and triglycerides (46.2±6 mg/dl), (p<0.001 for all variables). A significant decrease in HDL (28.3±1.14 mg/dl) in Group B vs. Group A (61±1.0 mg/dl) (p<0.001) validated the experimental MS model. Myeloperoxidase activity increased significantly in Group B (181.3±15.7 IU/ml) vs. Group A (116.07±4.2 IU/ml) (p<0.001). A similar behavior was seen with SOD antioxidant activity in Group B (181±6 U/ml) vs. Group A (138±3.6 U/ml) (p <0.01). Light microscopy of the heart and thoracic aorta revealed histopathological changes in animals with induced MS. Conclusion: Increased MPO and SOD in Group B would indicate the presence of OS in MS, with consequences at the vascular level.

Effect of dietary copper addition on lipid metabolism in rabbits

ABSTRACTThe present study was conducted to investigate the effect of copper supplementation on lipid metabolism in rabbits. Our study showed dietary copper addition (5-45 mg/kg) increased body mass gain, but decreased fat and liver weights compared with those in the control group (P < 0.05). Copper (45 mg/kg) addition significantly increased the skeletal muscle weight, but inhibited cytoplasmic lipid accumulation in liver, skeletal muscle and adipose tissue (P < 0.05). Compared with the control group, dietary copper addition (45 mg/kg) significantly increased plasma triglyceride levels but decreased very low density lipoprotein levels (P < 0.05). Copper treatment significantly increased gene expression of carnitine palmitoyltransferase (CPT) 1, CPT2 and peroxisome proliferator-activated receptor (PPAR) a in liver (P < 0.05). In skeletal muscle, CPT1, CPT2, fatty acid transport protein, fatty acid-binding protein, and PPARa mRNA as well as phosphorylated AMP-activated protein kinase (AMPK) levels were significantly up-regulated by copper treatment (P < 0.05). Rabbits receiving copper supplementation had higher CPT1, CPT2, PPARa and hormone-sensitive lipase mRNA levels in adipose tissue (P < 0.05). In conclusion, copper promoted skeletal muscle growth and reduced fat accretion. PPARa signaling in liver, skeletal muscle and adipose tissues and AMPK signaling in skeletal muscle tissue were involved in the regulation of lipid metabolism by copper.

Intravenous Glucose Acutely Stimulates Intestinal Lipoprotein Secretion in Healthy Humans.

Increased production of intestinal triglyceride-rich lipoproteins (TRLs) contributes to dyslipidemia and increased risk of atherosclerotic cardiovascular disease in insulin resistance and type 2 diabetes. We have previously demonstrated that enteral glucose enhances lipid-stimulated intestinal lipoprotein particle secretion. Here, we assessed whether glucose delivered systemically by intravenous infusion also enhances intestinal lipoprotein particle secretion in humans. On 2 occasions, 4 to 6 weeks apart and in random order, 10 healthy men received a constant 15-hour intravenous infusion of either 20% glucose to induce hyperglycemia or normal saline as control. Production of TRL-apolipoprotein B48 (apoB48, primary outcomes) and apoB100 (secondary outcomes) was assessed during hourly liquid-mixed macronutrient formula ingestion with stable isotope enrichment and multicompartmental modeling, under pancreatic clamp conditions to limit perturbations in pancreatic hormones (insulin and glucagon) and growth hormone. Compared with saline infusion, glucose infusion induced both hyperglycemia and hyperinsulinemia, increased plasma triglyceride levels, and increased TRL-apoB48 concentration and production rate (P<0.05), without affecting TRL-apoB48 fractional catabolic rate. No significant effect of hyperglycemia on TRL-apoB100 concentration and kinetic parameters was observed. Short-term intravenous infusion of glucose stimulates intestinal lipoprotein production. Hyperglycemia may contribute to intestinal lipoprotein overproduction in type 2 diabetes. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02607839.

A CpG-SNP Located within the ARPC3 Gene Promoter Is Associated with Hypertriglyceridemia in Severely Obese Patients

Aims: To test the potential association of cytosine-phosphate-guanine dinucleotides (CpG)-single-nucleotide polymorphisms (SNPs) located within actin-related protein 2/3 complex subunit 3 (ARPC3), a gene recently linked to adipogenesis and lipid accumulation, with metabolic syndrome (MetS) features in severely obese patients. Methods: Prioritized SNPs within the ARPC3 locus were genotyped and tested for associations with MetS features in a cohort of 1,749 obese patients with and without MetS. Association testing with CpG methylation levels was performed in a methylation sub-cohort of 16 obese men. Results: A significant association was found between the CpG-SNP rs3759384 (C>T) and plasma triglyceride (TG) levels (false discovery rate-corrected p = 3.5 × 10^-2), with 0.6% of the phenotypic variance explained by the CpG-SNP, and with TT homozygotes showing the highest plasma TG levels (1.89 mmol/l). The carriers of the rs3759384 T allele also showed a significant decrease in methylation levels of the ARPC3 promoter-associated CpG site cg10738648 in both visceral adipose tissue and blood. ARPC3 expression levels showed a strong correlation with plasma TG levels (r = 0.70; p = 0.02). Conclusions: The increased plasma TG levels found in homozygous rs3759384 T allele carriers argue for a relevant role of this CpG-SNP in lipid management among obese individuals, which may be driven by an epigenetic-mediated mechanism.

ANGPTL4 variants E40K and T266M are associated with lower fasting triglyceride levels and predicts cardiovascular disease risk in Type 2 diabetic Tunisian population.

BackgroundAngiopoietin-like protein 4 (ANGPTL4) is a metabolic factor that increases plasma triglyceride levels by inhibiting lipoprotein lipase (LPL). The objective of this study was to investigate the association of ANGPTL4 variants (E40K and T266M) with triglyceride levels and with cardiovascular risk factors, such as metabolic syndrome (MetS) and obesity in type 2 diabetic Tunisian population.MethodsWe investigated the effect of the tagging single nucleotide polymorphisms (SNPs) rs1044250 (T266M) and rs116843064 (E40K) with triglyceride (TG) levels and CAD risk factors in a cohort of 220 patients undergoing coronary angiography for the evaluation of stable CAD, all of whom had (type 2 diabetes) T2D and were at least overweight. Multivariate logistic regressions were performed on association studies.ResultsTT genotype of rs1044250 (T266M variant) showed a protective effect on CVD risk in CAD group patients (OR 1.92, 95 % CI 0.601.42, p =0.05) compared with control Group patients (OR 1.17, 95 % CI 0.70–1.66, p = 0.72). Likewise, GA genotype of rs116843064 (E40K variant): (OR 0.74, 95 % CI 0.54–1.65, p =0.01) for the CAD group compared with control Group patients (OR 1.12, 95 % CI 0.68–1.74, p = 0.074).ConclusionsANGPTL4 variants are associated with, not only lower fasting triglyceride levels, but also a decreased cardiovascular risk in T2D Tunisian patients. So, T266M and E40K polymorphism predicts cardiovascular disease risk in Type 2 diabetic Tunisian population

Hepatoprotective effect of resveratrol against ethanol-induced oxidative stress through induction of superoxide dismutase in vivo and in vitro.

The present study aimed to investigate the hepatoprotective effect of resveratrol (RSV) against ethanol-induced oxidative stress in vivo, and investigate the underlying mechanisms by which RSV exerts its anti-oxidative effects on hepatic cells. C57BL/6J mice were divided into four groups: Untreated control, ethanol-treated, RSV-treated, and ethanol + RSV-treated. The plasma lipid profile, hepatic lipid accumulation and antioxidative enzyme activities were analyzed. HepG2 cells were used as a cellular model to analyze the effects of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and peroxisome proliferator-activated receptors (PPARs) in the RSV-mediated protection of ethanol-induced oxidative stress. In C57BL/6J mice, ethanol caused a significant increase in plasma triglyceride levels and hepatic lipid accumulation (P<0.05), whereas RSV notably increased SOD activity. In HepG2 cells, SOD activity was enhanced in the RSV-treated HepG2 cells, whereas the activity of CAT and GPx was not affected. Western blot and quantitative polymerase chain reaction analyses demonstrated that RSV significantly increased SOD protein and mRNA expression levels (P<0.05). Using a transient transfection assay, PPARγ was observed to participate in the regulation of SOD gene expression in RSV-administered HepG2 cells. To conclude, the results from the present study suggest that RSV may contribute towards the protection of hepatic cells from ethanol-induced oxidative stress via the induction of SOD activity and gene expression.

Antihyperlipidemic effect of Acanthopanax senticosus (Rupr. et Maxim) Harms leaves in high-fat-diet fed mice.

Metabolic syndrome is a major risk factor for a variety of obesity-related diseases. Recently, the effects of functional foods have been investigated on lipid metabolism as a means to reduce lipid content in the blood, liver and adipose tissues associated with carnitine O-palmitoyltransferase (CPT) activity. Acanthopanax senticosus (Rupr. et Maxim) Harms (AS) is a medicinal herb possessing a wide spectra of functions including antioxidant, anti-inflammatory and anti-fatigue actions. Despite much research being focused on the cortical roots of AS, little information is available regarding its leaves, which are also expected to promote human health, for example by improving abnormal lipid metabolism. Here, we explored whether AS leaves affect lipid metabolism in mice fed a high-fat diet. The administration of AS to BALB/c mice fed a high-fat diet significantly decreased plasma triglycerides (TG). CPT activity in the liver of these mice was significantly enhanced by AS treatment. These findings indicate that AS leaves have the potential to alleviate increase in plasma TG levels due to high-fat diet intake in mice, possibly by increasing mitochondrial fatty acid β-oxidation, especially via CPT activation. Consequently, daily intake of AS leaves could promote beneficial health effects including the prevention of metabolic syndrome. © 2015 Society of Chemical Industry.

Immunoproteasome subunit LMP7 Deficiency Improves Obesity and Metabolic Disorders.

Inflammation plays an important role in the development of obesity and metabolic disorders; however, it has not been fully understood how inflammation occurs and is regulated in their pathogenesis. Low-molecular mass protein-7 (LMP7) is a proteolytic subunit of the immunoproteasome that shapes the repertoire of antigenic peptides on major histocompatibility complex class I molecule. In this study, we investigated the role of LMP7 in the development of obesity and metabolic disorders using LMP7-deficient mice. LMP7 deficiency conveyed resistant to obesity, and improved glucose intolerance and insulin sensitivity in mice fed with high-fat diet (HFD). LMP7 deficiency decreased pancreatic lipase expression, increased fecal lipid contents, and inhibited the increase of plasma triglyceride levels upon oral oil administration or HFD feeding. Using bone marrow-transferred chimeric mice, we found that LMP7 in both bone marrow- and non-bone marrow-derived cells contributes to the development of HFD-induced obesity. LMP7 deficiency decreased inflammatory responses such as macrophage infiltration and chemokine expression while it increased serum adiponection levels. These findings demonstrate a novel role for LMP7 and provide new insights into the mechanisms underlying inflammation in the pathophysiology of obesity and metabolic disorders.

Pregnancy-related severe hypertriglyceridemia

The increase in plasma triglyceride level in pregnancy is modest, but in those who have deficiencies in lipoprotein lipase or apolipoprotein C-II (i.e., familial hyperlipidemia), the increase in very LDL concentration cannot be controlled and results in severe hypertriglyceridemia. This case is related to severe primary hypertriglyceridemia (types V) detected on the 25th week of gestation and treated with regular therapeutic plasma exchange and later on with alternate plasmapheresis with donated plasma. No complications were observed. A healthy male baby was delivered on the 39th week of pregnancy. After giving birth, the maternal triglyceride levels showed a remarkable reduction.

Genetic Variants Associated with Gestational Hypertriglyceridemia and Pancreatitis

Severe hypertriglyceridemia is a well-known cause of pancreatitis. Usually, there is a moderate increase in plasma triglyceride level during pregnancy. Additionally, certain pre-existing genetic traits may render a pregnant woman susceptible to development of severe hypertriglyceridemia and pancreatitis, especially in the third trimester. To elucidate the underlying mechanism of gestational hypertriglyceridemic pancreatitis, we undertook DNA mutation analysis of the lipoprotein lipase (LPL), apolipoprotein C2 (APOC2), apolipoprotein A5 (APOA5), lipase maturation factor 1 (LMF1), and glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) genes in five unrelated pregnant Chinese women with severe hypertriglyceridemia and pancreatitis. DNA sequencing showed that three out of five patients had the same homozygous variation, p.G185C, in APOA5 gene. One patient had a compound heterozygous mutation, p.A98T and p.L279V, in LPL gene. Another patient had a compound heterozygous mutation, p.A98T & p.C14F in LPL and GPIHBP1 gene, respectively. No mutations were seen in APOC2 or LMF1 genes. All patients were diagnosed with partial LPL deficiency in non-pregnant state. As revealed in our study, genetic variants appear to play an important role in the development of severe gestational hypertriglyceridemia, and, p.G185C mutation in APOA5 gene appears to be the most common variant implicated in the Chinese population. Antenatal screening for mutations in susceptible women, combined with subsequent interventions may be invaluable in the prevention of potentially life threatening gestational hypertriglyceridemia-induced pancreatitis.

Effect of apolipoprotein C3 genetic polymorphisms on serum lipid levels and the risk of intracerebral hemorrhage.

BackgroundSerum lipid levels are associated with the risk of intracerebral hemorrhage (ICH). Genetic variants in the apolipoprotein C3 (APOC3) gene were associated with plasma triglyceride (TG) and very-low-density lipoprotein (VLDL) levels. The aim of this study was to evaluate the effect of two genetic variants (1100 C/T and 3238 C/G) of APOC3 on serum lipid levels and risk of ICH.MethodsA prospective hospital-based case–control design and logistic regression analysis were utilized. We enrolled 150 ICH patients and 150 age- and gender-matched controls. The APOC3 gene polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).ResultsICH patients had a significantly higher frequency of APOC3 3238 GG genotype [odds ratio (OR) =2.97, 95 % confidence interval (CI) = 1.20, 7.38; P = 0.02] and APOC3 3238 G allele (OR =1.53, 95 % CI = 1.03, 2.27; P = 0.04) than controls. The APOC3 3238 G allele was significantly associated with increasing plasma TG levels and VLDL levels both in ICH cases (P = 0.01) and controls (P = 0.02). No association was found between APOC3 1100 C/T polymorphisms and ICH.ConclusionTo the best of our knowledge, this is the first report in the literature that the APOC3 3238 GG genotype and G allele might contribute to an increased risk of ICH as a result of its effect on serum lipid levels.

PAPEL DE LOS ANTICONCEPTIVOS CON PROGESTÁGENO SOLO EN MUJERES CON FACTORES DE RIESGO

Existen condiciones clínicas en las cuales los anticonceptivos combinados orales podrían implicar riesgos, especialmente cardiovasculares. En estas situaciones el uso de anticonceptivos con progestágeno solo (APS) podría ser una buena alternativa. Así por ejemplo, en mujeres con mayor riesgo trombótico, tanto arterial como venoso, el uso de algunos anticonceptivos combinados puede aumentar el riesgo de accidente cerebrovascular, infarto del miocardio o tromboembolismo venoso, lo que no se ha observado con la APS. Tampoco se ha descrito que su uso aumente el riesgo trombótico en fumadoras mayores de 35 años, como lo hacen los anticonceptivos combinados. La AP5 sería también una buena indicación en hipertrigliceridemia, ya que el etinilestradiol aumenta los niveles plasmáticos de triglicéridos. Por otra parte, como con la mayor edad y/o con la obesidad se incrementa la prevalencia de factores de riesgo, en ambas condiciones puede ser también adecuado el uso de APS. En hipertensas, dado la probabilidad de aumento de cifras tensionales inducidas por los estrógenos, es también recomendable su utilización. Su principal desventaja sería que no tienen un adecuado control de ciclos, como el dado por los anticonceptivos combinados. CONCLUSIONES: Los anticonceptivos con sólo progestágenos son una buena alternativa en mujeres con riesgos o con contraindicaciones.

Detraining in pregnancy and/or lactation modulates neuropeptidergic hypothalamic systems in offspring mice.

Manipulations in metabolic parameters during pregnancy/lactation can impact the development of short- and long-term energy control mechanisms, which are mainly modulated by neural and hormonal inputs to the hypothalamus. Thus, we tested how mice training and detraining during pregnancy and lactation affect hypothalamus gene expression and change biometric and metabolic profiles of the offspring. Three-month-old female Swiss mice were submitted to an 8-week exercise program (swimming 5 times/week, 1 h/day). Following this physical exercise protocol, these conditioned animals and the control group were submitted to matting. After pregnancy verification, the animals were distributed into four groups: training during pregnancy and lactation (T); detraining after pregnancy confirmation (DP); detraining during lactation (DL); and control (CT), without interventions. After weaning, the offspring of the four groups were derived into these as follows: TO, DPO, DLO, and CTO, respectively. The body weight was lower in conditioned females compared to control at weeks 4-8 of the exercise regimen. No statistical difference in dam's body weight was observed during pregnancy. Related to offspring, at post-natal day 90, the animals were euthanized and DPO and DLO showed decrease in Npy and Cart expression in hypothalamus, and DLO also had increased Lep gene expression in white adipose tissue. Additionally, DPO showed increase in plasma triglycerides levels, total liver weight, and decrease in brown adipose tissue compared to CTO. Together, these results support that detraining during critical periods of development leads to altered gene expression in hypothalamic neuropeptidergic systems.

Anthocyanin-rich Phytochemicals from Aronia Fruits Inhibit Visceral Fat Accumulation and Hyperglycemia in High-fat Diet-induced Dietary Obese Rats.

Aronia fruits (chokeberry: Aronia melanocarpa E.) containing phenolic phytochemicals, such as cyanidin 3-glycosides and chlorogenic acid, have attracted considerable attention because of their potential human health benefits in humans including antioxidant activities and ability to improved vision. In the present study, the effects of anthocyanin-rich phytochemicals from aronia fruits (aronia phytochemicals) on visceral fat accumulation and fasting hyperglycemia were examined in rats fed a high-fat diet (Experiment 1). Total visceral fat mass was significantly lower in rats fed aronia phytochemicals than that in both the control group and bilberry phytochemicals-supplemented rats (p < 0.05). Moreover, perirenal and epididymal adipose tissue mass in rats fed aronia phytochemicals was significantly lower than that in both the control and bilberry phytochemicals group. Additionally, the mesenteric adipose tissue mass in aronia phytochemicals-fed rats was significantly low (p < 0.05). Furthermore, the fasting blood glucose levels significantly decreased in rats fed aronia phytochemicals for 4 weeks compared to that in the control rats (p < 0.05). Therefore, we investigated the effects of phytochemicals on postprandial hyperlipidemia after corn oil loading in rats, pancreatic lipase activity in vitro, and the plasma glycemic response after sucrose loading in order to elucidate the preventive factor of aronia phytochemical on visceral fat accumulation. In the oral corn oil tolerance tests (Experiment 2), aronia phytochemicals significantly inhibited the increases in plasma triglyceride levels, with a half-maximal inhibitory concentration (IC(50)) of 1.50 mg/mL. However, the inhibitory activity was similar to that of bilberry and tea catechins. In the sucrose tolerance tests (Experiment 3), aronia phytochemicals also significantly inhibited the increases in blood glucose levels that were observed in the control animals (p < 0.05). These results suggest that anthocyanin-rich phytochemicals in aronia fruits suppress visceral fat accumulation and hyperglycemia by inhibiting pancreatic lipase activity and/or intestinal lipid absorption.