Potential Value of Probiotics on Lipid Profiles in Hyperlipidemia and Healthy Participants: Systematic Review and Meta-Analysis.

Objective: Many randomized controlled trials (RCTs) have reported the effect of probiotics on reducing plasma lipids with inconsistent results. An explicit systematic review and meta-analysis were conducted in this study to evaluate the effect of probiotics on the lipid profile of healthy and hyperlipidemia participants. Methods: A comprehensive literature search of RCTs was conducted using PubMed, Embase, World Health Organization (WHO) Global Index Medicus, WHO clinical trial registry, and Clinicaltrials.gov. Inclusion criteria included RCTs comparing the use of any strain of a specified probiotic with the placebo control group. The change in lipid profiles was analyzed. Results: The probiotics can decrease the total cholesterol (TC) level in hyperlipidemia participants but not healthy persons (MD = -0.43, 95% CI -0.60 - -0.25, P < .01; MD = -0.09, 95% CI -0.26 - 0.08, P > .05). Probiotics did not reduce high-density lipoprotein cholesterol (HDL-C) in patients with hyperlipidemia or healthy people (MD = -0.01, 95% CI -0.09 - 0.07, P > .05; MD = 0.02, 95% CI -0.04 - 0.09, P > .05). Furthermore, probiotics can reduce the low-density lipoprotein cholesterol (LDL-C) level both in hyperlipidemia and healthy persons (MD = -0.34, 95% CI -0.43 - -0.26, P < .01; MD = -0.15, 95% CI -0.28 - -0.02, P < .05). Lastly, the effect of probiotics on reducing triglyceride (TG) levels was significant in hyperlipidemia persons but not in the healthy population (MD = -0.20, 95% CI -0.37 - -0.04, P < .01; MD = -0.01, 95% CI -0.02 - 0.04, P > .05). Conclusions: Through our analysis, the effect of probiotics on lowering plasma lipid was more obvious in hyperlipidemia participants than healthy population. However, further studies are required to confirm the findings due to pronounced clinical heterogeneity.

[Specialized fat-and-oil emulsion food systems for the prevention of hyperlipidemia and obesity].

The development of specialized fat-and-oil emulsion food systems for the prevention of hyperlipidemia and obesity is an important task of health concern in the Russian Federation. The aim of the study was to develop specialized fat-and-oil emulsion food systems for the prevention of hyperlipidemia and obesity, the distinctive features of which are the presence of functional ingredients and bioactive compounds that meet modern safety requirements, have a hypolipidemic effect and influence on body weight. Material and methods. As a source of fucoxanthin, an oil extract from the thallom (stratum) of the annual Undaria pinnatifida brown algae was used, obtained by re-extraction with soy oil for 8 hours from a glycerin extract (extractant - 60% glycerin solution, the duration of the process - 8 h). The determination of organoleptic parameters was carried out at a temperature of 20 °C 12 h after manufacture using standard methods. Organoleptic parameters were determined in the following sequence: consistency, appearance, color, smell, taste. Physical and chemical characteristics (mass content of fat, moisture, egg products in terms of dry yolk, acidity in terms of acetic acid, emulsion stability), acid and peroxide values were studied by standard methods. Fatty acid analysis of lipids was performed by gas-liquid chromatography. The fucoxanthin content was determined by spectrophotometric method. Results. The presented formulations of lipid compositions as the fat base of specialized oil-fat emulsion food systems for the prevention of hyperlipidemia and obesity included Schizochytrium sp. microalgae oil in a mass fraction of 3-6% as a source of ω-3 polyunsaturated fatty acids (PUFAs) (eicosapentaenoic and docosahexaenoic acids). An oil extract of U. pinnatifida brown algae in a mass fraction of 48-54% was used as a source of fucoxanthin. The total content of PUFA was significantly high - at least 73%, ω-6 PUFA prevailed (48.0-49.1%). However, the high content of ω-3 PUFA (at least 25%) should be also noted. The ratio of ω-3 to ω-6 PUFA was 1:1.72-1:1.90, which is atypical for individual vegetable oils traditionally used as the fat phase in fat-and-oil emulsion systems. The fucoxanthin content in the presented lipid compositions was 6.4-7.2 mg/100 ml. Edible fat-and-oil emulsion food systems for the prevention of hyperlipidemia and obesity (mayonnaise and mayonnaise sauces) with a given ratio of ω-3:ω-6 PUFA containing eicosopentaenoic and docosahexaenoic acids, as well as fucoxanthin, have been obtained. The extract of U. pinnatifida brown algae, containing fucoxanthin, significantly slowed down the processes of lipid oxidation and hydrolysis, as evidenced by changes in the peroxide and acid values of fat isolated from specialized fat-and-oil emulsion systems for the prevention of hyperlipidemia and obesity. Conclusion. Specialized fat-and-oil emulsion food systems for the prevention of hyperlipidemia and obesity (mayonnaise and mayonnaise sauces with different oil phase content), containing fucoxanthin, having an optimized fatty acid composition, a given ratio of ω-3:ω-6 PUFA, high content of essential PUFA (eicosopentaenoic and docosohexaenoic acids) are safe food products with traditional organoleptic characteristics and specified physical and chemical parameters.

Nobiletin Prevents High-Fat Diet-Induced Dysregulation of Intestinal Lipid Metabolism and Attenuates Postprandial Lipemia.

OBJECTIVE: Nobiletin is a dietary flavonoid that improves insulin resistance and atherosclerosis in mice with metabolic dysfunction. Dysregulation of intestinal lipoprotein metabolism contributes to atherogenesis. The objective of the study was to determine if nobiletin targets the intestine to improve metabolic dysregulation in both male and female mice. Approach and Results: Triglyceride-rich lipoprotein (TRL) secretion, intracellular triglyceride kinetics, and intestinal morphology were determined in male and female LDL (low-density lipoprotein) receptor knockout (Ldlr-/-), and male wild-type mice fed a standard laboratory diet or high-fat, high-cholesterol (HFHC) diet ± nobiletin using an olive oil gavage, radiotracers, and electron microscopy. Nobiletin attenuated postprandial TRL levels in plasma and enhanced TRL clearance. Nobiletin reduced fasting jejunal triglyceride accumulation through accelerated TRL secretion and lower jejunal fatty acid synthesis with no impact on fatty acid oxidation. Fasting-refeeding experiments revealed that nobiletin led to higher levels of phosphorylated AKT (protein kinase B) and FoxO1 (forkhead box O1) and normal Srebf1c expression indicating increased insulin sensitivity. Intestinal length and weight were diminished by HFHC feeding and restored by nobiletin. Both fasting and postprandial plasma GLP-1 (glucagon-like peptide-1; and likely GLP-2) were elevated in response to nobiletin. Treatment with a GLP-2 receptor antagonist, GLP-2(3-33), reduced villus length in HFHC-fed mice but did not impact TRL secretion in any diet group. In contrast to males, nobiletin did not improve postprandial lipid parameters in female mice. CONCLUSIONS: Nobiletin opposed the effects of the HFHC diet by normalizing intestinal de novo lipogenesis through improved insulin sensitivity. Nobiletin prevents postprandial lipemia because the enhanced TRL clearance more than compensates for increased TRL secretion.

Exercise to Lower Postprandial Lipemia: Why, When, What and How.

We review recent findings on the ability of exercise to lower postprandial lipemia (PPL). Specifically, we answer why exercise is important in lowering PPL, when it is most effective to exercise to achieve this, what the preferred exercise is and how exercise reduces PPL. Most findings confirm the power of exercise to lower PPL, which is an independent risk factor for cardiovascular disease. Exercise is most effective when performed on the day preceding a high- or moderate-fat meal. This effect lasts up to approximately two days; therefore, one should exercise frequently to maintain this benefit. However, the time of exercise relative to a meal is not that important in real-life conditions, since one consumes several meals during the day; thus, an exercise bout will inevitably exert its lowering effect on PPL in one or more of the subsequent meals. Although moderate-intensity continuous exercise, high-intensity intermittent exercise, resistance exercise and accumulation of short bouts of exercise throughout the day are all effective in lowering PPL, submaximal, high-volume interval exercise seems to be superior, provided it is tolerable. Finally, exercise reduces PPL by both lowering the rate of appearance and increasing the clearance of triacylglycerol-rich lipoproteins from the circulation.

Circulating Rather Than Intestinal PCSK9 (Proprotein Convertase Subtilisin Kexin Type 9) Regulates Postprandial Lipemia in Mice.

OBJECTIVE: Increased postprandial lipemia (PPL) is an independent risk factor for atherosclerotic cardiovascular diseases. PCSK9 (Proprotein convertase subtilisin kexin type 9) is an endogenous inhibitor of the LDLR (low-density lipoprotein receptor) pathway. We previously showed that PCSK9 inhibition in mice reduces PPL. However, the relative contribution of intracellular intestinal PCSK9 or liver-derived circulating PCSK9 to this effect is still unclear. Approach and Results: To address this issue, we generated the first intestine-specific Pcsk9-deficient (i-Pcsk9-/-) mouse model. PPL was measured in i-Pcsk9-/- as well as in wild-type and streptozotocin-induced diabetic mice following treatment with a PCSK9 monoclonal antibody (alirocumab). Blocking the circulating form of PCSK9 with alirocumab significantly reduced PPL, while overexpressing human PCSK9 in the liver of full Pcsk9-/- mice had the opposite effect. Alirocumab regulated PPL in a LDLR-dependent manner as this effect was abolished in Ldlr-/- mice. In contrast, i-Pcsk9-/- mice did not exhibit alterations in plasma lipid parameters nor in PPL. Finally, PPL was highly exacerbated by streptozotocin-induced diabetes mellitus in Pcsk9+/+ but not in Pcsk9-/- mice, an effect that was mimicked by the use of alirocumab in streptozotocin-treated Pcsk9+/+ mice. CONCLUSIONS: Taken together, our data demonstrate that PPL is significantly altered by full but not intestinal PCSK9 deficiency. Treatment with a PCSK9 monoclonal antibody mimics the effect of PCSK9 deficiency on PPL suggesting that circulating PCSK9 rather than intestinal PCSK9 is a critical regulator of PPL. These data validate the clinical relevance of PCSK9 inhibitors to reduce PPL, especially in patients with type 2 diabetes mellitus.

Preventive role of propolis against hyperglycemia and hyperlipidemia in Sprague dawley rats (Rattus norvegicus) animal modelling system.

Human diets with functional ingredients showed promising role in management of diseases of modern age like hyperglycemia and hyperlipidemia and even cancer. The study designed to elucidate role of honeybee propolis for management of hyperglycemia and hyperlipidemia states through animal modeling system. Hydroalcoholic extract of propolis was used for development of functional drink with standard recipe and addition of specified dose of extracts (400mg/500mL). Animals were grouped into three studies including study-I fed on regular diet, study-II fed on sucrose enrich diet and study-III fed on diet enriched with cholesterol and monitored to evaluate the results. Various parameters like feed consumption, liquid intake of animals measured regularly whereas body weight recorded at the end of each week of study. At the end of the study animals were analyzed for different blood indicators like blood lipid indices (cholesterol, LDL, HDL concentration and triglyceride contents)), glucose concentration and insulin contents as well. The maximum feed and drink intake were examined in animals, fed with control diet whereas a non substantial mode of intake was recorded in rest of two groups of animals. The consumption of honeybee propolis based drink reduced cholesterol (6.63% to 10.25%) and LDL (9.96% to 11.23%), whilst a sharp increase in HDL level was ranged as 4.12 to 4.49% among animal groups fed with high cholesterol and high sucrose diet. Blood glucose level was decreased by 10.25% and 6.98% however 6.99% and 4.51% increase were observed in plasma insulin level in both studies, study-II and study-III correspondingly. The overall findings of the study showed that drinks prepared using propolis of propolis found effective for management of hyperglycemia and hypercholesterolemia in present animal modelling system.

Clearing the Clutter: Antiatherosclerotic activity of Eucalyptus camaldulensis crude extract.

Plant components have been extensively evaluated for their pharmacological activities. This study provides scientific rationale towards the therapeutic effect of Eucalyptus camaldulensis aqueous bark extract against induced atherosclerosis and hyperlipidemia in pigeons. Phytochemical components of Eucalyptus bark extract possess a great antioxidant activity that potentially reduced the risk of heart diseases. A total of 42 Pigeons of both sexes were distributed into negative control (fed normal grain diet), hyperlipidemic control (fed HFD 1% animal fat oil and 0.1% cholesterol for 3 months), test groups of variable doses (0.05, 0.1, 0.2 to 0.4 gms/kg BW for 21 days) and the group received atorvastatin daily after induction used. At the end of the experiment biochemical and histological evaluation has been performed. After HFD induction the serum levels of liver enzyme AST, glucose, urea, cholesterol, LDL, VLDL, and TG were significantly increased with the reduction in HDL levels. The atherogenic index was also found significantly raised. Microscopic examination of the liver and aorta showed the appearance of lipid-filled foam cells all over the liver parenchyma and intima after the HFD induction. Thus it was concluded that Eucalyptus aqueous bark extract can be effective against atherosclerosis and hyperlipidemia.

Cardiovascular disease risk assessment for Aboriginal and Torres Strait Islander adults aged under 35 years: a consensus statement.

Cardiovascular disease (CVD) is a leading cause of preventable morbidity and mortality in Aboriginal and Torres Strait Islander peoples. This statement from the Australian Chronic Disease Prevention Alliance, the Royal Australian College of General Practitioners, the National Aboriginal Community Controlled Health Organisation and the Editorial Committee for Remote Primary Health Care Manuals communicates the latest consensus advice of guideline developers, aligning recommendations on the age to commence Aboriginal and Torres Strait Islander CVD risk assessment across three guidelines. MAIN RECOMMENDATIONS: In Aboriginal and Torres Strait Islander peoples without existing CVD: CVD risk factor screening should commence from the age of 18 years at the latest, including for blood glucose level or glycated haemoglobin, estimated glomerular filtration rate, serum lipids, urine albumin to creatinine ratio, and other risk factors such as blood pressure, history of familial hypercholesterolaemia, and smoking status. Individuals aged 18-29 years with the following clinical conditions are automatically conferred high CVD risk: ▶type 2 diabetes and microalbuminuria; ▶moderate to severe chronic kidney disease; ▶systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 110 mmHg; ▶familial hypercholesterolaemia; or ▶serum total cholesterol > 7.5 mmol/L. Assessment using the National Vascular Disease Prevention Alliance absolute CVD risk algorithm should commence from the age of 30 years at the latest - consider upward adjustment of calculated CVD risk score, accounting for local guideline use, risk factor and CVD epidemiology, and clinical discretion. Assessment should occur as part of an annual health check or opportunistically. Subsequent review should be conducted according to level of risk. CHANGES IN MANAGEMENT AS A RESULT OF THIS STATEMENT: From age 18 years (at the latest), Aboriginal and Torres Strait Islander adults should undergo CVD risk factor screening, and from age 30 years (at the latest), they should undergo absolute CVD risk assessment using the NVDPA risk algorithm.

Starch sources influence lipidaemia of diabetic dogs.

BACKGROUND: Hyperlipidaemia is considered a cause of other diseases that are clinically important and potentially life threatening. Combination of pea and barley as exclusive starch sources is known to interfere with glycemic control in diabetic dogs, but their effect on lipid profile of hiperlipidaemic dogs is yet to be evaluated. Twelve adult diabetic dogs were fed three dry extruded diets with different starch sources and different fat levels: peas and barley (PB), maize (Mi), and peas, barley and rice (Ba) with 15.7, 15.6 and 9.0% of their dry matter as fat, respectively. Plasmatic cholesterol and triglycerides concentration curves over 10 h were obtained after 60 days on each diet and with the same NPH insulin dose. ANOVA test or Friedman test were used to compare the dietary effects on triglycerides and cholesterol variables among the diets. RESULTS: Dogs presented lower mean (p = 0.05), fasting (p = 0.03), and time 8-h postprandial (p = 0.05) triglyceridemia after PB diet period than Ba diet period and time 4-h postprandial (p = 0.02) lower after PB than Mi diet. Cholesterolemia mean, minimum, maximum, area under the cholesterol curve and times points: 2, 4, 6, 8 and 10-h postprandial, had lower values after PB ingestion in comparison to Mi, without difference to Ba diet. CONCLUSION: Inclusion of pea and barley, as exclusive starch sources, in therapeutic diets for diabetic dogs can minimize plasmatic triglycerides and cholesterol concentration at fasting and at different postprandial time, compared to the maize diet or diet with lesser fat content.

The acute effects of interrupting prolonged sitting with stair climbing on vascular and metabolic function after a high-fat meal.

PURPOSE: Frequent consumption of high-fat meals and prolonged sedentary time are prevalent lifestyles that have been associated with an increased risk of vascular and metabolic complications. This study evaluated the acute effects of interrupting prolonged sitting with stair climbing on vascular and metabolic function after a high-fat meal. METHODS: In a randomized, cross-over trial, 12 healthy adults (age: 23.5 ± 2.9 years) consumed a high-fat meal, followed by either 1) a 4-h uninterrupted sitting (sitting trial) or 2) a 4-h sitting interrupted with a 5-min stair climbing (average intensity: 66% of heart rate reserve) every hour (interrupted trial). Plasma triglyceride and glucose concentrations, as well as popliteal artery blood flow and shear rate were assessed at baseline and every hour after a high-fat meal, whereas brachial artery flow-mediated dilation was assessed at baseline and again at the end of each trial. RESULTS: Plasma triglyceride and glucose concentrations increased after a high-fat meal and returned to baseline at the end of both trials. Following a high-fat meal, brachial artery flow-mediated dilation decreased in the sitting trial, but not in the interrupted trial (sitting trial: 9.65 ± 2.63% to 7.84 ± 2.36%; interrupted trial: 9.41 ± 2.61% to 10.34 ± 3.30%, p = 0.009 for interaction). Compared with the sitting trial, the interrupted trial improved popliteal blood flow and shear rate (p = 0.004 and p = 0.008 for interaction, respectively). CONCLUSIONS: These findings suggest that interrupting prolonged sitting with stair climbing may be an effective lifestyle strategy to prevent against vascular dysfunction that might occur as a result of prolonged sitting after consuming a high-fat meal in young healthy adults.

Beneficial Effects of SREBP Decoy Oligodeoxynucleotide in an Animal Model of Hyperlipidemia.

Hyperlipidemia is a chronic disorder that plays an important role in the development of cardiovascular diseases, type II diabetes, atherosclerosis, hypertension, and non-alcoholic fatty liver disease. Hyperlipidemias have created a worldwide health crisis and impose a substantial burden not only on personal health but also on societies and economies. Transcription factors in the sterol regulatory element binding protein (SREBP) family are key regulators of the lipogenic genes in the liver. SREBPs regulate lipid homeostasis by controlling the expression of a range of enzymes required for the synthesis of endogenous cholesterol, fatty acids, triacylglycerol, and phospholipids. Thereby, SREBPs have been considered as targets for the treatment of metabolic diseases. The aim of this study was to investigate the beneficial functions and the possible underlying molecular mechanisms of SREBP decoy ODN, which is a novel inhibitor of SREBPs, in high-fat diet (HFD)-fed hyperlipidemic mice. Our studies using HFD-induced hyperlipidemia animal model revealed that SREBB decoy ODN inhibited the increased expression of fatty acid synthetic pathway, such as SREBP-1c, FAS, SCD-1, ACC1, and HMGCR. In addition, SREBP decoy ODN decreased pro-inflammatory cytokines, including TNF-α, IL-1ß, IL-8, and IL-6 expression. These results suggest that SREBP decoy ODN exerts its anti-hyperlipidemia effects in HFD-induced hyperlipidemia mice by regulating their lipid metabolism and inhibiting lipogenesis through inactivation of the SREPB pathway.

1H-NMR Metabolomics Analysis of the Effect of Rubusoside on Serum Metabolites of Golden Hamsters on a High-Fat Diet.

Rubusoside is a natural sweetener and the active component of Rubus suavissimus. The preventive and therapeutic effect of rubusoside on high-fat diet-induced (HFD) serum metabolite changes in golden hamsters was analyzed by 1H-NMR metabolomics to explore the underlying mechanism of lipid metabolism regulation. 1H-NMR serum metabolomics analyses revealed a disturbed amino acid-, sugar-, fat-, and energy metabolism in HFD animals. Animals supplemented with rubusoside can partly reverse the metabolism disorders induced by high-fat diet and exerted good anti-hypertriglyceridemia effect by intervening in some major metabolic pathways, involving amino acid metabolism, synthesis of ketone bodies, as well as choline and 4-hydroxyphenylacetate metabolism. This study indicates that rubusoside can interfere with and normalize high-fat diet-induced metabolic changes in serum and could provide a theoretical basis to establish rubusoside as a potentially therapeutic tool able to revert or prevent lipid metabolism disorders.

Hypolipidemic potential of sterol containing fractions of Jolyna laminarioides: a brown alga.

Solvent fractions (n-hexane, cholorofrom, methanol) and fractions containing sterols of Jolyna laminarioides was evaluated in triton-induced and high-fat-diet induced hyperlipidemic rats. Oral administration of J. laminarioides significantly reduced the elevated level of serum total cholesterol, triglycerides and LDL-c, both in triton induced and high fat diet induced hyperlipidemic rat models with increased serum HDL-c. Chloroform: methanol fraction (2:1) and n-hexane fraction containing sterol showed promising results in reducing LDL-c. The methanol fraction showed hypolipidemic effect by increasing HDL-c (90%). The extracts and fractions of the seaweed also decreased the increased level of cardiac and hepatic marker enzymes beside lowering lipid profile. J. laminarioides exhibited high anti-hyperlipidemic effects both in triton induced and high fat diet induced hyperlipidemic rats.

Non-HDL cholesterol should not generally replace LDL cholesterol in the management of hyperlipidaemia.

PURPOSE OF REVIEW: Non-HDL cholesterol was originally conceived as a therapeutic target for statin treatment in hypertriglyceridaemia when apolipoprotein B100 assays were not widely available. Recently non-HDL cholesterol has been recommended to replace LDL cholesterol in the clinical management of dyslipidaemia routinely in general medical practice. This is misguided. RECENT FINDINGS: Non-HDL cholesterol is heterogeneous, constituting a mixture of triglyceride-rich VLDL, intermediate density lipoprotein and LDL in which small dense LDL is poorly represented and to which VLDL cholesterol contributes increasingly as triglyceride levels rise. This makes it unsuitable as a goal of lipid-lowering treatment or as an arbiter of who should receive such treatment. Results of trials designed to lower LDL cholesterol are not easily translated to non-HDL cholesterol. Fasting is no longer thought essential for screening the general population for raised LDL cholesterol. ApoB100 measurement also does not require fasting even in rarer more extreme lipoprotein disorders encountered in the Lipid Clinic, provides greater precision and specificity and overcomes the problems posed by LDL and non-HDL cholesterol. It is more easily interpreted both in diagnosis and as a therapeutic goal and it includes SD-LDL. SUMMARY: If we are to discourage use of LDL cholesterol, it should be in favour of apoB100 not non-HDL cholesterol.

Absence of gravin-mediated signaling inhibits development of high-fat diet-induced hyperlipidemia and atherosclerosis.

Gravin, an A-kinase anchoring protein, is known to play a role in regulating key processes that lead to inflammation and atherosclerosis development, namely, cell migration, proliferation, and apoptosis. We investigated the role of gravin in the development of high-fat diet (HFD)-induced atherosclerosis and hyperlipidemia. Five-week-old male wild-type (WT) and gravin-t/t mice were fed a normal diet or an HFD for 16 wk. Gravin-t/t mice showed significantly lower liver-to-body-weight ratio, cholesterol, triglyceride, and very low-density lipoprotein levels in serum as compared with WT mice on HFD. Furthermore, there was less aortic plaque formation coupled with decreased lipid accumulation and liver damage, as the gravin-t/t mice had lower levels of serum alanine aminotransferase and aspartate aminotransferase. Additionally, gravin-t/t HFD-fed mice had decreased expression of liver 3-hydroxy-3-methyl-glutaryl-CoA reductase, an essential enzyme for cholesterol synthesis and lower fatty acid synthase expression. Gravin-t/t HFD-fed mice also exhibited inhibition of sterol regulatory element binding protein-2 (SREBP-2) expression, a liver transcription factor associated with the regulation of lipid transportation. In response to platelet-derived growth factor receptor treatment, gravin-t/t vascular smooth muscle cells exhibited lower intracellular calcium transients and decreased protein kinase A- and protein kinase C-dependent substrate phosphorylation, notably involving the Erk1/2 signaling pathway. Collectively, these results suggest the involvement of gravin-dependent regulation of lipid metabolism via the reduction of SREBP-2 expression. The absence of gravin-mediated signaling lowers blood pressure, reduces plaque formation in the aorta, and decreases lipid accumulation and damage in the liver of HFD mice. Through these processes, the absence of gravin-mediated signaling complex delays the HFD-induced hyperlipidemia and atherosclerosis.NEW & NOTEWORTHY The gravin scaffolding protein plays a key role in the multiple enzymatic pathways of lipid metabolism. We have shown for the first time the novel role of gravin in regulating the pathways related to the initiation and progression of atherosclerosis. Specifically, an absence of gravin-mediated signaling decreases the lipid levels (cholesterol, triglyceride, and VLDL) that are associated with sterol regulatory element binding protein-2 downregulation.

Ophiopogonin D alleviates high-fat diet-induced metabolic syndrome and changes the structure of gut microbiota in mice.

Gut dysbiosis is believed to play a critical role in the pathogenesis of metabolic diseases, including obesity. Ophiopogonin D (OP-D), a steroidal glycoside and an active component extracted from the root of the plant Ophiopogon japonicus (also known as radix ophiopogonis), can regulate multiple physiologic processes. Here we show that OP-D administration reduces body weight, hyperglycemia, hyperlipidemia, and insulin resistance in male mice fed a high-fat diet (HFD). Pyrosequencing of the V4 regions of 16S rRNA genes in mouse feces revealed a deviation of the gut microbiota in response to OP-D treatment. In particular, the decreased Firmicutes-to- Bacteroidetes ratios and endotoxin-bearing Proteobacteria levels indicated that OP-D reversed HFD-induced gut dysbiosis. More importantly, the effects of OP-D on modulation of obesity and microbiota were transferable via horizontal feces transfer from OP-D-treated mice to HFD-fed mice. Taken together, our results suggest that OP-D may be used as a prebiotic agent to treat obesity-associated gut dysbiosis and metabolic syndrome.-Chen, S., Li, X., Liu, L., Liu, C., Han, X. Ophiopogonin D alleviates high-fat diet-induced metabolic syndrome and changes the structure of gut microbiota in mice.

Safety and tolerability of high-intensity statin therapy in heart transplant patients receiving immunosuppression with tacrolimus.

BACKGROUND: Following heart transplantation (HT), HMG CoA reductase inhibitors (statins) have been shown to reduce total and low-density lipoprotein (LDL) cholesterol, development of cardiac allograft vasculopathy (CAV), and mortality. Studies in HT patients have demonstrated the safety of low/moderate intensity statins; however, little data exist using high-intensity (HI) statins. The study aim was to evaluate the safety and efficacy of HI statins in HT recipients receiving tacrolimus. METHODS: This single-center, retrospective analysis included adult HT recipients from January 1, 2005, to December 31, 2015, who received HI statin therapy during posttransplant follow-up. The primary outcome, tolerability, was defined as the absence of myalgias, hepatotoxicity, rhabdomyolysis, or HI statin dose reduction/discontinuation. The secondary end point was the mean reduction in total and LDL cholesterol. RESULTS: Among the 24 patients included, one experienced myalgias and therapy discontinuation (4%; P > 0.99). No other HI statin dose reduction/discontinuation occurred, and no instances of rhabdomyolysis or hepatotoxicity were observed. The average reduction in total and LDL cholesterol after conversion to HI statin was 35 mg/dL (P = 0.02) and 19 mg/dL (P = 0.10), respectively. CONCLUSIONS: High-intensity statin therapy appears safe and efficacious in HT recipients receiving tacrolimus and is a reasonable option for the treatment of refractory hyperlipidemia.

Heparin-binding EGF-like growth factor (HB-EGF) antisense oligonucleotide protected against hyperlipidemia-associated atherosclerosis.

BACKGROUND AND AIMS: Heparin-binding EGF-like growth factor (HB-EGF) is a representative EGF family member that interacts with EGFR under diverse stress environment. Previously, we reported that the HB-EGF-targeting using antisense oligonucleotide (ASO) effectively suppressed an aortic aneurysm in the vessel wall and circulatory lipid levels. In this study, we further examined the effects of the HB-EGF ASO administration on the development of hyperlipidemia-associated atherosclerosis using an atherogenic mouse model. METHODS AND RESULTS: The male and female LDLR deficient mice under Western diet containing 21% fat and 0.2% cholesterol content were cotreated with control and HB-EGF ASOs for 12 weeks. We observed that the HB-EGF ASO administration effectively downregulated circulatory VLDL- and LDL-associated lipid levels in circulation; concordantly, the HB-EGF targeting effectively suppressed the development of atherosclerosis in the aorta. An EGFR blocker BIBX1382 administration suppressed the hepatic TG secretion rate, suggesting a positive role of the HB-EGF signaling for the hepatic VLDL production. We newly observed that there was a significant improvement of the insulin sensitivity by the HB-EGF ASO administration in a mouse model under the Western diet as demonstrated by the improvement of the glucose and insulin tolerances. CONCLUSION: The HB-EGF ASO administration effectively downregulated circulatory lipid levels by suppressing hepatic VLDL production rate, which leads to effective protection against atherosclerosis in the vascular wall.

Olanzapine Induced Dysmetabolic Changes Involving Tissue Chromium Mobilization in Female Rats.

Atypical antipsychotics, such as olanzapine, are commonly prescribed to patients with schizophrenic symptoms and other psychiatric disorders. However, weight gain and metabolic disturbance cause adverse effects, impair patient compliance and limit clinical utility. Thus, a better understanding of treatment-acquired adverse effects and identification of targets for therapeutic intervention are believed to offer more clinical benefits for patients with schizophrenia. Beyond its nutritional effects, studies have indicated that supplementation of chromium brings about beneficial outcomes against numerous metabolic disorders. In this study, we investigated whether olanzapine-induced weight gain and metabolic disturbance involved chromium dynamic mobilization in a female Sprague-Dawley rat model, and whether a dietary supplement of chromium improved olanzapine-acquired adverse effects. Olanzapine medicated rats experienced weight gain and adiposity, as well as the development of hyperglycemia, hyperinsulinemia, insulin resistance, hyperlipidemia, and inflammation. The olanzapine-induced metabolic disturbance was accompanied by a decrease in hepatic Akt and AMP-activated Protein Kinase (AMPK) actions, as well as an increase in serum interleukin-6 (IL-6), along with tissue chromium depletion. A daily intake of chromium supplements increased tissue chromium levels and thermogenic uncoupling protein-1 (UCP-1) expression in white adipose tissues, as well as improved both post-olanzapine weight gain and metabolic disturbance. Our findings suggest that olanzapine medicated rats showed a disturbance of tissue chromium homeostasis by inducing tissue depletion and urinary excretion. This loss may be an alternative mechanism responsible for olanzapine-induced weight gain and metabolic disturbance.

Hypolipidemic and antioxidant activities of volatile oils from fresh leaves of Michelia martini Levl.

.This study aimed to investigate the hypolipidemic and antioxidant activities of volatile oils from Michelia martini Levl. The antioxidant property of volatile oils from Michelia martini in vitro was investigated by establishment of various systems. High fat diet induced rats were used to assess the hypolipidemic and antioxidant activities of Michelia martini volatile oils in vivo. The level of total cholesterol, triglycerides, high density lipoprotein cholesterol, low density lipoprotein cholesterol, alanine transaminase, aspartate aminotransferase, alkaline phosphatase and gamma-glutamyl transpeptidase in serum, and the activities of catalase, malondialdehyde, super oxide dismutase and glutathione in liver of rats were assayed by standard procedures. Our results showed that Michelia martini exhibits strong hypolipidemic and antioxidant activities both in vitro and vivo. Our data were also supplemented with histopathological studies on liver tissues and aorta sections of rats.