Low Dose Monacolin K Combined with Coenzyme Q10, Grape Seed, and Olive Leaf Extracts Lowers LDL Cholesterol in Patients with Mild Dyslipidemia: A Multicenter, Randomized Controlled Trial.

Certain nutraceuticals, mainly containing red yeast rice, might be considered as an alternative therapy to statins in patients with dyslipidemia, although there is still insufficient evidence available with respect to long-term safety and effectiveness on cardiovascular disease prevention and treatment. The aim of this study was to assess the lipid-lowering activity and safety of a dietary supplement containing a low dose of monacolin K combined with coenzyme Q10, grape seed and olive tree leaf extracts in patients with mild hypercholesterolemia. In total, 105 subjects with mild hypercholesterolemia (low-density lipoprotein cholesterol LDL-C levels 140-180 mg/dL) and low CV risk were randomly assigned into three treatment groups: lifestyle modification (LM), LM plus a low dosage of monacolin K (3 mg), and LM plus a high dosage of monacolin K (10 mg) and treated for 8 weeks. The primary endpoint was the reduction of LDL-C and total cholesterol (TC). LDL-C decreased by 26.46% on average (p < 0.001) during treatment with 10 mg of monacolin and by 16.77% on average during treatment with 3 mg of monacolin (p < 0.001). We observed a slight but significant reduction of the triglyceride levels only in the high-dose-treated group (mean -4.25%; 95% CI of mean -11.11 to 2.61). No severe adverse events occurred during the study. Our results confirm the LDL-C-lowering properties of monacolin are clinically meaningful even in lower doses of 3 mg/day.

Digeda-4 decoction and its disassembled prescriptions improve dyslipidemia and apoptosis by regulating AMPK/SIRT1 pathway on tyloxapol-induced nonalcoholic fatty liver disease in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Nonalcoholic fatty liver disease (NAFLD) is a manifestation of metabolic syndrome in the liver and the leading cause of chronic liver disease worldwide. Digeda-4 decoction (DGD-4) is a commonly prescribed Mongolian herbal drug for treating acute and chronic liver injury and fatty liver. However, the mechanisms underlying the improvement of dislipidemia and liver injury via treatment with DGD-4 remain unclear. Disassembling a prescription is an effective approach to studying the effects and mechanisms underlying Mongolian medicine prescriptions. By disassembling a prescription, it is feasible to discover effective combinations of individual herbs to optimize a given prescription. Accordingly, we disassembled DGD-4 into two groups: the single Lomatogonium rotatum (L.) Fries ex Nym (LR) (DGD-1) and non-LR (DGD-3). AIM OF THIS STUDY: To study whether DGD-4 and its disassembled prescriptions have protective effects against tyloxapol (TY)-induced NAFLD and to explore the underlying mechanisms of action and compatibility of prescriptions. MATERIAL AND METHODS: NAFLD mice were developed by TY induction. Biochemical horizontal analyses, enzyme-linked immunosorbent assay, and liver histological staining were performed to explore the protective effects of DGD-4 and its disassembled prescriptions DGD-3 and DGD-1. Furthermore, we performed immunohistochemical analyses and Western blotting to further explore the expression of target proteins. RESULTS: DGD-4 and its disassembled prescriptions could inhibit TY-induced dislipidemia and liver injury. In addition, DGD-4 and its disassembled prescriptions increased the levels of p-AMPKα and p-ACC, but decreased the levels of SREBP1c, SCD-1, SREBP-2, and HMGCS1 proteins. The activation of lipid metabolic pathways SIRT1, PGC-1α, and PPARα improved lipid accumulation in the liver. Moreover, DGD-4 could inhibit hepatocyte apoptosis and treat TY-induced liver injury by upregulating the Bcl-2 expression, downregulating the expression of Bax, caspase-3, caspase-8, and the ratio of Bax/Bcl-2, and positively regulating the imbalance of oxidative stress (OxS) markers (such as superoxide dismutase [SOD], catalase [CAT], malondialdehyde [MDA], and myeloperoxidase [MPO]). DGD-1 was superior to DGD-3 in regulating lipid synthesis-related proteins such as SREBP1c, SCD-1, SREBP-2, and HMGCS1. DGD-3 significantly affected the expression of lipid metabolic proteins SIRT1, PGC-1α, PPARα, apoptotic proteins Bcl-2, Bax, caspase-3, caspase-8, and the regulation of Bax/Bcl-2 ratio. However, DGD-1 showed no regulatory effects on Bax and Bcl-2 proteins. CONCLUSION: This study demonstrates the protective effects of DGD-4 in the TY-induced NAFLD mice through a mechanism involving improvement of dyslipidemia and apoptosis by regulating the AMPK/SIRT1 pathway. Although the Monarch drug DGD-1 reduces lipid accumulation and DGD-3 inhibits apoptosis and protects the liver from injury, DGD-4 can be more effective overall as a therapy when compared to DGD-1 and DGD-3.

Caffeic acid regulates glucose homeostasis and inhibits purinergic and cholinergic activities while abating oxidative stress and dyslipidaemia in fructose-streptozotocin-induced diabetic rats.

OBJECTIVES: The antidiabetic potential of caffeic acid in fructose/streptozotocin-induced type 2 diabetic rats was examined in this study. METHODS: Male Sprague-Dawley rats were supplied with 10% fructose solution for 14 days followed by an intraperitoneal injection of 40 mg/kg bw streptozotocin to induce type 2 diabetes (T2D). Rats were treated with both low (150 mg/kg bw) and high (300 mg/kg bw) doses of caffeic acid for 5 weeks, while the positive control group was treated with metformin (200 mg/kg bw). KEY FINDINGS: Treatment with caffeic acid significantly decreased blood glucose levels and elevated serum insulin levels while improving glucose tolerance, pancreatic ß-cell function and morphology. It also led to a significant reduction of serum cholesterol, triglyceride, LDL-cholesterol, ALT, AST, creatinine, urea and uric acid levels, while increasing HDL cholesterol levels. Caffeic acid significantly (P < 0.05) elevated hepatic glycogen level, serum and pancreatic glutathione level, superoxide dismutase and catalase activities with a concomitant decrease in malondialdehyde level, α-amylase, lipase, adenosine triphosphatase (ATPase), ectonucleoside triphosphate diphosphohydrolase (ENTPDase), 5'-nucleotidase (5'-NTD) and acetylcholinesterase activities. CONCLUSION: The results suggest caffeic acid as a potent natural product with therapeutic effects against T2D. Further molecular and clinical studies are, however, required to ascertain these findings.

Protective Effects of Green Tea Supplementation against Lead-Induced Neurotoxicity in Mice.

The use of natural products as therapeutic agents is rapidly growing recently. In the current study, we investigated the protective effects of green tea supplementation on lead-induced toxicity in mice. Forty albino mice were divided into four groups as follows: A: control group; B: green tea receiving group; C: lead-intoxicated group; and D: lead-intoxicated group supplemented with green tea. At the end of the experiment, the animals were tested for neurobehavioral and biochemical alterations. Green tea was analyzed through Gas Chromatography-Mass Spectrometry (GC/MS) analysis. We found that supplementation with green tea ameliorated the lead-associated increase in body weight and blood glucose. Green tea supplementation also changed the blood picture that was affected due to lead toxicity and ameliorated lead-induced dyslipidemia. The group of mice that were supplemented with green tea has shown positive alterations in locomotory, anxiety, memory, and learning behaviors. The GC/MS analysis revealed many active ingredients among which the two most abundant were caffeine and 1,2-benzenedicarboxylic acid, mono(2-ethylhexyl) ester. We concluded that green tea supplementation has several positive effects on the lead-induced neurotoxicity in mice and that these effects may be attributed to its main two active ingredients.

In vivo, Lipid Profile Efficacy of Ethanol Extracts of Stevia rebaudiana Bertoni in Rabbits.

BACKGROUND AND OBJECTIVE: Contraceptive pills are chemical substances used as a means to prevent pregnancy, but they have several effects, including high lipid profile and in many cases, patients with heart and blood diseases cannot use it as a contraceptive helps in increasing the risk of cardiovascular diseases (CVD). A Stevia extract with high sweetening capacity due to its content of glycosides is used to reduce lipid profile and this study aimed to decrease lipid profile levels and lowering the risk factor in women using contraceptive drugs by stevia extracts. MATERIALS AND METHODS: Sixteen rabbits have been used as a case-control study design due to their anatomical and physiological similarity to humans. The stevia leaves are extracted using Soxhlet apparatus of ethanol solvent. Statistical package (SPSS), were used for data analysis and management using independent sample t-test, test, comparison of means for lipid profile of Triglyceride (TG), Cholesterol, High-density lipoprotein (HDL-C), Low-density lipoprotein (LDL-C) between (di-contraceptive, mono-contraceptive and control groups). RESULTS: The results showed increasing cholesterol and LDL-C during the combined oral contraceptive (COCP) and progesterone-only pills with decreased HDL-C level. A comparison of means before and after stevia used explains the elevated HDL-C and decreased LDL-C. CONCLUSION: The lipid profile levels should continuously be monitored during oral contraceptive intake and Stevia leaf powder extraction is suggested to reduce the risk of CVD.

Vildagliptin, a dipeptidyl peptidase-4 inhibitor, reduces betel-nut induced carcinogenesis in female mice.

AIM: Betel-nut, a popular masticatory among Southeast Asian populations is a class I carcinogen, previously associated with dyslipidemia and aberrant lipid metabolism, and is reported to be used more frequently by females, than males. This study investigates the potential of repurposing the anti-diabetic drug, vildagliptin, a dipeptidyl peptidase-4 inhibitor, for alleviating the oncogenic condition in female Swiss Albino mice administered an aqueous extract of betel-nut (AEBN) orally (2 mg ml-1) for 24 weeks. MAIN METHODS: Tissues were investigated by histopathological, immunohistochemical and apoptosis assays. Biochemical analyses of oxidative stress markers and lipid profile were performed using different tissues and sera. The expressions of different proteins involved in lipid metabolism and oncogenic pathways were evaluated by Western blotting. KEY FINDINGS: AEBN induced carcinogenesis primarily in the liver by significantly impairing AMPK signaling, inducing oxidative stress, activating Akt/mTOR signaling, increasing Ki-67 immunoreactivity and cyclin D1 expression, and significantly diminishing apoptosis. Co-administration of AEBN with vildagliptin (10 mg kg-1 body weight) for 8 weeks reduced liver dysplasia, and significantly decreased free palmitic acid, increased free oleic acid, normalized lipid profile, decreased oxidative stress, cyclin D1 expression, Ki-67 immunoreactivity, and Bcl2 expression, and increased the ratio of apoptotic/non-apoptotic cells. Mechanistically, vildagliptin elicited these physiological and molecular alterations by restoring normal AMPK signaling and reducing the cellular expressions of FASN and HMGCR, restoring AMPK-dependent phosphorylation of p53 at Ser-15 and reducing Akt/mTOR signaling. SIGNIFICANCE: These results indicate that vildagliptin may alleviate betel-nut induced carcinogenesis in the liver of female mice.

Matcha Improves Metabolic Imbalance-Induced Cognitive Dysfunction.

This study was conducted to assess the protective effect of extract of match (EM) on high-fat diet- (HFD-) induced cognitive deficits in male C57BL/6 mice. It was found that EM improved glucose tolerance status by measuring OGTT and IPGTT with HFD-induced mice. EM protected behavioral and memory dysfunction in Y-maze, passive avoidance, and Morris water maze tests. Consumption of EM reduced fat mass, dyslipidemia, and inflammation in adipose tissue. Also, EM ameliorated hepatic and cerebral antioxidant systems. EM improved the cerebral cholinergic system by regulating ACh contents and expression of AChE and ChAT. Also, EM restored mitochondrial function in liver and brain tissue. EM attenuated hepatic inflammatory effect, lipid synthesis, and cholesterol metabolism by regulating the protein expression of TNF-α, TNFR1, p-IRS-1, p-JNK, IL-1ß, iNOS, COX-2, HMGCR, PPARγ, and FAS. Finally, EM regulated cognitive function and neuroinflammation in the whole brain, hippocampus, and cerebral cortex by regulating the protein expression of p-JNK, p-Akt, p-tau, Aß, BDNF, IDE, COX-2, and IL-1ß. These findings suggest that EM might be a potential source of functional food to improve metabolic disorder-associated cognitive dysfunction.

Effect of Ocimum gratissimum Leaf-extract on Hematological Indices and Lipid Profile of Streptozotocin-induced Diabetic Wistar Rats.

BACKGROUND AND OBJECTIVE: Ocimum gratissimum (OG) has been used in ethnopharmacology for the treatment of diabetes. The aim of the study was to evaluate the effect of Ocimum gratissimum leaf-extract on hematological indices and lipid profile of Streptozotocin-induced diabetic Wistar rats. MATERIALS AND METHODS: Twenty-four rats weighing 100-160 g were randomly assigned to four treatment groups, the normal and diabetic controls, received a placebo treatment, while groups three and four were administered glibenclamide and OG leaf-extract (400 mg kg-1 b.wt.), respectively. The extracts were administered twice daily for 28 days. The rats were sacrificed and whole blood was collected for hematological and serum lipid profile assays. Data were analyzed using one-way ANOVA. RESULTS: Diabetes induction resulted in decreases (p<0.05) in Red Blood Cell (RBC), Hemoglobin (Hb), White Blood Cell (WBC) and increases in Mean Corpuscular Hemoglobin and Blood platelets compared to the normal control. Treatment with O. gratissimum extract reversed RBC (7.74±0.39 µL), WBC (16.57±3.02) and Platelet (804.33±194.02) levels, but not Hb, towards normal levels (7.99±0.04, 11.27±0.69, 839.67±10.17 respectively). Diabetes induction also resulted in increases (p<0.05) in Triglyceride (TG) and Very-Low-Density Lipoprotein (VLDL), decreases (p<0.05) in High-Density Lipoprotein (HDL) and Low-Density Lipoprotein (LDL) compared to normal control with no significant change in Total Cholesterol (TC). After administration with Ocimum gratissimum TC, LDL and VLDL and HDL levels were significantly (p<0.05) reduced relative to the diabetic control. TG was however increased relative to the diabetic control. CONCLUSION: Overall, data suggests the plant holds great potential in amelioration of diabetes-induced dyslipidemia and hematological disorders.

Dacryodes edulis (G. Don) H.J. Lam modulates glucose metabolism, cholinergic activities and Nrf2 expression, while suppressing oxidative stress and dyslipidemia in diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Dacryodes edulis L. is an evergreen tree indigenous to western and eastern Africa which is utilized for nutritional and medicinal purposes. Folklorically, different parts of the tree are used in treating and managing diabetes and its complications. AIMS: The antidiabetic effect of the butanol fraction of D. edulis ethanol extract (BFDE) was studied in fructose-streptozotocin induced type 2 diabetic rats. METHODS: The ethanol extract was fractionated to yield the hexane, dichloromethane, ethyl acetate, butanol and aqueous fractions. The in vitro antidiabetic activities of the fractions were determined by their ability to inhibit α-glucosidase activity. BDFE was the most active and showed no cytotoxic effect while stimulating glucose uptake in 3T3-L1 adipocytes. Thus, selected for in vivo study. Diabetic rats were grouped into 4. The negative control group was administered water only, another group was treated with metformin (200 mg/kg bodyweight), while the other groups were administered BDFE at 150 and 300 mg/kg bodyweight respectively. Two other groups consisting of normal rats were given water and BFDE (300 mg/kg bodyweight) respectively, with the former serving as normal control. After 6 weeks of intervention, the rats were humanely sacrificed using appropriate anaesthesia. RESULTS: Treatment with the fraction significantly (p < 0.05) reduced the blood glucose level of the diabetic rats, with concomitant increase in serum insulin secretion. It also caused significant (p < 0.05) elevation of reduced glutathione level, superoxide dismutase, catalase, α-amylase, and ATPase activities, with concomitant depletion in myeloperoxidase activity, NO and MDA levels of the serum and pancreas. The pancreatic morphology and ß-cell function were significantly improved in BFDE-treated rats, with restoration of the pancreatic capillary networks. Treatment with BFDE significantly (p < 0.05) inhibited the activities of glycogen phosphorylase, fructose 1,6 biphosphatase, glucose 6 phosphatase, and acetylcholinesterase, while suppressing the expression of Nrf2. HPLC analysis revealed the presence of gallic acid, vanillic acid, vanillin, and (-)-epicatechin in the fraction. CONCLUSION: These results portray the antidiabetic and antioxidative properties of BFDE, which may be a synergistic consequence of the identified phenolics.

Diets with low n-6:n-3 PUFA ratio protects rats from fructose-induced dyslipidemia and associated hepatic changes: Comparison between 18:3 n-3 and long-chain n-3 PUFA.

In the present study, we investigated the impact of substituting alpha-linolenic acid (ALA) or long-chain n-3 PUFA (eicosapentaenoic acid and docosahexaenoic acid) for linoleic acid and hence decreasing n-6:n-3 PUFA ratio on high-fructose diet-induced hypertriglyceridemia and associated hepatic changes. Weanling male Wistar rats were divided into four groups and fed with starch-diet (n-6:n-3 PUFA ratio 215:1) and high-fructose diets with different n-6:n-3 PUFA ratio (215:1, 2:1 with ALA and 5:1 with long-chain n-3 PUFA) for twenty-four weeks. Substitution of linoleic acid with ALA (n-6:n-3 PUFA ratio of 2) or long-chain n-3 PUFA (n-6:n-3 PUFA ratio of 5) protected the rats from fructose-induced dyslipidemia, hepatic oxidative stress and corrected lipogenic and proinflammatory gene expression. Both ALA and long-chain n-3 PUFA supplementation also reversed the fructose-induced upregulation of 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) gene, which is involved in the generation of active glucocorticoids in tissues. Although both ALA and LC n-3 PUFA prevented fructose-induced dyslipidemia to a similar extent, compared to ALA, LC n-3 PUFA is more effective in preventing hepatic oxidative stress and inflammation.

Are dietary fish oil supplements appropriate for dyslipidemia management? A review of the evidence.

PURPOSE OF REVIEW: The purpose of this review is to assess whether dietary fish oil supplements can be appropriate for patients with elevated triglycerides and cardiovascular risk based on a comprehensive analysis of their composition, and level of regulatory oversight. RECENT FINDINGS: Approximately 19 million people in the United States take fish oil supplements, many for the purpose of treating or preventing heart disease. Unlike prescription products, fish oil supplements are classified as food by the Food and Drug Administration (FDA) and are not required to undergo manufacturing oversight or clinical testing. Analysis of widely used dietary fish oil supplements show that they may have lower amounts of ω-3 than advertised as well as significant levels of saturated fat and oxidized oils which actually may contribute to dyslipidemia. Clinical outcome trials have failed to show a consistent cardiovascular benefit with fish oil supplements and other low-dose mixed ω-3 fatty acids. SUMMARY: In light of limited regulatory oversight and evidence of quality concerns, dietary fish oil supplements are not an appropriate substitute for FDA approved prescription ω-3 fatty acids for their indicated use in treatment of elevated triglycerides or the prevention of cardiovascular events.

Role of angiopoietin-like protein 3 in sugar-induced dyslipidemia in rhesus macaques: suppression by fish oil or RNAi.

Angiopoietin-like protein 3 (ANGPTL3) inhibits lipid clearance and is a promising target for managing cardiovascular disease. Here we investigated the effects of a high-sugar (high-fructose) diet on circulating ANGPTL3 concentrations in rhesus macaques. Plasma ANGPTL3 concentrations increased ∼30% to 40% after 1 and 3 months of a high-fructose diet (both P < 0.001 vs. baseline). During fructose-induced metabolic dysregulation, plasma ANGPTL3 concentrations were positively correlated with circulating indices of insulin resistance [assessed with fasting insulin and the homeostatic model assessment of insulin resistance (HOMA-IR)], hypertriglyceridemia, adiposity (assessed as leptin), and systemic inflammation [C-reactive peptide (CRP)] and negatively correlated with plasma levels of the insulin-sensitizing hormone adropin. Multiple regression analyses identified a strong association between circulating APOC3 and ANGPTL3 concentrations. Higher baseline plasma levels of both ANGPTL3 and APOC3 were associated with an increased risk for fructose-induced insulin resistance. Fish oil previously shown to prevent insulin resistance and hypertriglyceridemia in this model prevented increases of ANGPTL3 without affecting systemic inflammation (increased plasma CRP and interleukin-6 concentrations). ANGPTL3 RNAi lowered plasma concentrations of ANGPTL3, triglycerides (TGs), VLDL-C, APOC3, and APOE. These decreases were consistent with a reduced risk of atherosclerosis. In summary, dietary sugar-induced increases of circulating ANGPTL3 concentrations after metabolic dysregulation correlated positively with leptin levels, HOMA-IR, and dyslipidemia. Targeting ANGPTL3 expression with RNAi inhibited dyslipidemia by lowering plasma TGs, VLDL-C, APOC3, and APOE levels in rhesus macaques.

Association of single nucleotide polymorphisms with dyslipidemia in antiretroviral exposed HIV patients in a Ghanaian population: A case-control study.

Dyslipidemia is a potential complication of long-term usage of antiretroviral therapy (ART) and also known to be associated with genetic factors. The host genetic variants associated with dyslipidemia in HIV patients on ART in Ghana have not been fully explored. The study constituted a total of 289 HIV-infected patients on stable ART for at least a year. Fasting blood was collected into EDTA tube for lipids measurement. Lipid profiles were used to define dyslipidemia based on the NCEP-ATP III criteria. HIV-infected subjects were categorized into two groups; those with dyslipidemia (cases) (n = 90; 31.1%) and without dyslipidemia (controls)(n = 199; 68.9%). Four candidate single nucleotide polymorphism (SNP) genes (ABCA1-rs2066714, LDLR-rs6511720, APOA5-rs662799 and DSCAML1-rs10892151) were determined. Genotyping was performed on isolated genomic DNA of study participants using PCR followed by a multiplex ligation detection reaction (LDR). The percentage of the population who had the rare homozygote alleles for rs6511720 (T/T), rs2066714 (G/G), rs10892151 (T/T) and rs662799 (G/G) among case subjects were 5.5%, 14.4%, 6.6% and 10.0% whiles 2.0% 9.1%, 6.5% and 4.0% were observed among control subjects. There were statistically significant differences in the genotypic prevalence of APOA5 (p = 0.0357) and LDLR polymorphisms (p = 0.0387) between case and control subjects. Compared to the AA genotype of the APOA5 polymorphisms, individuals with the rare homozygote genotype [aOR = 2.38, 95%CI(1.06-6.54), p = 0.004] were significantly associated with an increased likelihood of developing dyslipidemia after controlling for age, gender, treatment duration, CD4 counts and BMI. Moreover, individuals with the rare homozygous genotype of ABCA1 (G/G) [aOR = 10.7(1.3-88.7), p = 0.0280] and LDLR (rs6511720) G>T [aOR = 61.2(7.6-493.4), p<0.0001) were more likely to have high levels of total cholesterol levels. Our data accentuate the presence of SNPs in four candidate genes and their association with dyslipidemia among HIV patients exposed to ART in the Ghanaian population, especially variants in APOA5-rs662799 and LDLR rs6511720 respectively. These findings provide baseline information that necessitates a pre-symptomatic strategy for monitoring dyslipidemia in ART-treated HIV patients. There is a need for longitudinal studies to validate a comprehensive number of SNPs and their associations with dyslipidemia.

Pectin reduces environmental pollutant-induced obesity in mice through regulating gut microbiota: A case study of p,p'-DDE.

BACKGROUND: The prevalence of obesity has raised global concerns. Environmental pollutants are one of the main causes of obesity. Many studies have demonstrated that dietary fiber could reduce obesity induced by high-fat diets, but whether environmental pollutant-induced obesity can be reversed is still unknown. OBJECTIVES: This study aimed to investigate the effects of pectin on obesity induced by a typical environmental pollutant p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) and explore the underlying mechanism by which pectin reversed p,p'-DDE-induced obesity. METHODS: p,p'-DDE was used to induce obesity in C57BL/6J mice and pectin was supplied during and after cessation of p,p'-DDE exposure. Body and fat weight gain, plasma lipid profile and insulin resistance of mice were assessed. Gut microbiota composition and the levels of short-chain fatty acids (SCFAs) as well as the receptor proteins and hormones in the SCFAs-related signaling pathway were analyzed. Moreover, p,p'-DDE levels in various tissues of mice were detected. RESULTS: Pectin supplementation reversed body and fat weight gain, dyslipidemia, hyperglycemia and insulin resistance in p,p'-DDE-exposed mice. Furthermore, pectin apparently altered the p,p'-DDE-induced microbial composition and then promoted the levels of SCFAs in colonic feces as well as the expression of G-protein coupled receptors and the concentration of hormone peptide YY (PYY) and glucagon like peptide-1 (GLP-1). Pectin treatment also significantly reduced p,p'-DDE accumulation in mice tissues during p,p'-DDE exposure but did not change p,p'-DDE metabolism after termination of p,p'-DDE exposure. CONCLUSIONS: Pectin had a good effect on reducing p,p'-DDE-induced obesity through regulating gut microbiota and provided a potential strategy for the treatment of environmental pollutant-caused health problems.

Tissue-dependent effects of cis-9,trans-11- and trans-10,cis-12-CLA isomers on glucose and lipid metabolism in adult male mice.

Mixtures of the two major conjugated linoleic acid (CLA) isomers trans-10,cis-12-CLA and cis-9,trans-11-CLA are used as over the counter supplements for weight loss. Because of the reported adverse effects of CLA on insulin sensitivity in some mouse studies, we sought to compare the impact of dietary t10c12-CLA and c9t11-CLA on liver, adipose tissue, and systemic metabolism of adult lean mice. We fed 8 week-old C57Bl/6J male mice with low fat diets (10.5% Kcal from fat) containing 0.8% t10c12-CLA or c9t11-CLA for 9 or 38 days. Diets containing c9t11-CLA had minimal impact on the endpoints studied. However, 7 days after starting the t10c12-CLA diet, we observed a dramatic reduction in fat mass measured by NMR spectroscopy, which interestingly rebounded by 38 days. This rebound was apparently due to a massive accumulation of lipids in the liver, because adipose tissue depots were visually undetectable. Hepatic steatosis and the disappearance of adipose tissue after t10c12-CLA feeding was associated with elevated plasma insulin levels and insulin resistance, compared to mice fed a control diet or c9t11-CLA diet. Unexpectedly, despite being insulin resistant, mice fed t10c12-CLA had normal levels of blood glucose, without signs of impaired glucose clearance. Hepatic gene expression and fatty acid composition suggested enhanced hepatic de novo lipogenesis without an increase in expression of gluconeogenic genes. These data indicate that dietary t10c12-CLA may alter hepatic glucose and lipid metabolism indirectly, in response to the loss of adipose tissue in mice fed a low fat diet.

Lycopene-Rich Extract from Red Guava (Psidium guajava L.) Decreases Plasma Triglycerides and Improves Oxidative Stress Biomarkers on Experimentally-Induced Dyslipidemia in Hamsters.

This work assessed the effects of a 28-day treatment with lycopene-rich extract (LRE) from red guava fruit (Psidium guajava L.) on the lipid profile and oxidative stress in an experimental model of dyslipidemia. Male hamsters (116.5 ± 2.16 g) were fed with the AIN 93G diet containing casein (20%), coconut fat (13.5%) and cholesterol (0.1%). The animals were divided into four groups: normolipidemic control (standard feed; NC, n = 7); hypercholesterolemic control (HC, n = 7); LRE 25 mg/kg/day (LRE-25, n = 7) and LRE 50 mg/kg/day (LRE-50, n = 9). After treatment, plasma concentrations of triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL) cholesterol (LDL-c), high-density lipoprotein (HDL) cholesterol (HDL-c), malondialdehyde (MDA-p) and myeloperoxidase (MPO), as well as erythrocytic superoxide dismutase (SOD-e) and the atherogenic index, were determined. Malondialdehyde (MDA-h), catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD-h) levels were assessed. Feed intake (FI) and weight gain (WG) were also determined. The LRE-25 group presented significantly lower TG levels and atherogenic index than did the HC group (p < 0.05). Both LRE-25 and LRE-50 groups presented lower levels of MDA-p and MPO than did the HC group (p < 0.05). LRE demonstrated a promising effect against dyslipidemia and oxidative stress.

Dietary calcium status during maternal pregnancy and lactation affects lipid metabolism in mouse offspring.

Calcium plays important roles in lipid metabolism and adipogenesis, but whether its status in early life affects later lipid profiles needs to be clarified. Three to four-week old C57BL/6J female mice were fed with three different reproductive diets containing normal, low (insufficient) and high (excessive) calcium concentrations respectively throughout pregnancy and lactation. At postnatal 21 days, the weaning male and female pups from each group were sacrificed for experiments and the remaining were fed with the normal chow diet for 16 weeks. Meanwhile, some of the weaning female pups from maternal low calcium diet group were fed with the normal calcium, low calcium and high calcium mature diets respectively for 8 weeks. Maternal insufficient or excessive calcium status during pregnancy and lactation programmed an abnormal expression of hepatic and adipose genes (PPAR-γ, C/EBP-α, FABP4, Fasn, UCP2, PPAR-α, HMG-Red1, Acc1, and SREBP-1c) in the offspring and this may lead to dyslipidemia and accumulation of hepatic triglyceride (TG) and total cholesterol (TC) in later life. The effects of maternal calcium status on lipid metabolism were found only in the female adult offspring, but were similar between offspring males and females at postnatal 21 days. Additionally, the dyslipidemia and hepatic lipid accumulation caused by insufficient calcium status in early life may be reversed to some extent by dietary calcium supplementation in later life.

Dietary n-3 but not n-6 fatty acids down-regulate maternal dyslipidemia induced inflammation: A three-generation study in rats.

This study addresses the effects of n-3 and n-6 fatty acids in maternal dyslipidemia induced inflammation over three generation in rats. The detailed protocol for animal feeding and mating is described in the methodology. Placenta and fetal liver were isolated on the eighteenth day of gestation and delivered pups after lactation were kept on their maternal diets. Compared to control and experimental groups, high-fat fed rats (HFL) had a higher level of cytokines and eicosanoids in serum (p < 0.05). Liver and uterine expression of cPLA-2, Cox-2, 5-Lox, EP-1, BLT-1, and ICAM-1 were higher (p < 0.05) in HFL group. NF-kB and Nrf-2 levels in placenta and fetal liver were beneficially modulated by n-3 but not n-6 fatty acids. Offspring of dyslipidemic mothers' exhibit amplified inflammatory markers when continued on diets of their mothers. Incorporation of n-3 but not n-6 fatty acids down-regulated maternal dyslipidemia induced inflammatory markers.

Ameliorating effects of Sporidiobolus pararoseus extract on dyslipidemia in mice with high fat diet induced obesity.

The study investigated how an extract of Sporidiobolus pararoseus (S.p.) affects lipid metabolism in Kunming mice that were obese as a result of being fed a high-fat diet; the control group were administered Max EPA fish oil. Ten mice were randomly selected from a pool of 60 mice for the control group and the remaining 50 mice were fed with a high-fat diet to establish a dyslipidemia model. After 4 weeks, these 50 mice were randomly distributed among 5 groups: high-fat model group; Max EPA group; and 3 groups of mice fed different doses of S.p. extract (low dose, medium dose, and high dose). After 8 weeks, the mice were sacrificed and the relevant parameters were measured. Compared with the high-fat model group, the group administered the high dose of S.p. extract showed significantly decreased body mass and serum levels of total cholesterol, triglycerides, and low-density lipoprotein cholesterol, and increased levels of high-density lipoprotein cholesterol. The results from RT-PCR showed that the mRNA expression of sterol regulatory element-binding protein 1c, fatty acid synthesis enzyme, and acetyl-CoA carboxylase was lower in the groups supplemented with S.p. extract than in the high-fat model group, whereas the expression of carnitine palmitoyltransferase 1 was higher in the group supplemented with S.p. extract than in the high-fat model group. Our results suggest that taking S.p. extract could benefit patients with dyslipidemia. Therefore, S.p. extract should be developed as a dietary supplement to improve lipid metabolism in obese people.

The Effect of Phytosterol-Rich Fraction from Palm Fatty Acid Distillate on Blood Serum Lipid Profile of Dyslipidemia Rats.

Phytosterol-rich fraction (PRF) obtained from palm fatty acid distillate (PFAD) was investigated for its effect on blood serum lipid profile of dyslipidemia rats. Dyslipidemia was induced by force feeding cholesterol to five groups of rats; one group was a control or normal group. Cholesterol force-fed groups were treated with 0, 10, 20, 30, and 40 mg PRF/kg/day for 4 weeks. All groups of rats were fed standard diet. A normal group was fed standard diet without PRF treatment and cholesterol force feeding. Lipid profile was measured every week (0, 1, 2, 3, and 4). Four-week treatment resulted in significant blood serum lipid profile improvement. PRF improved blood serum lipid profile by decreasing total cholesterol, triglyceride, and low density lipoprotein (LDL) cholesterol level and increasing high density lipoprotein (HDL) cholesterol level. The doses of PRF significantly affected blood serum lipid profile as well as duration of PRF treatment. PRF inhibited cholesterol absorption, which delayed blood serum total cholesterol rise. Cholesterol absorption inhibition was also indicated by higher fecal cholesterol concentration after PRF feeding. These results indicate the beneficial effect of PRF in the treatment of dyslipidemia.