Reduced Plasma Cholesterol Research Articles

Opposing effects of HNP1 (α-defensin-1) on plasma cholesterol and atherogenesis.

Atherosclerosis, the predominant cause of death in well-resourced countries, may develop in the presence of plasma lipid levels within the normal range. Inflammation may contribute to lesion development in these individuals, but the underlying mechanisms are not well understood. Transgenic mice expressing α-def-1 released from activated neutrophils develop larger lipid and macrophage-rich lesions in the proximal aortae notwithstanding hypocholesterolemia caused by accelerated clearance of α-def-1/low-density lipoprotein (LDL) complexes from the plasma. The phenotype does not develop when the release of α-def-1 is prevented with colchicine. However, ApoE-/- mice crossed with α-def-1 mice or given exogenous α-def-1 develop smaller aortic lesions associated with reduced plasma cholesterol, suggesting a protective effect of accelerated LDL clearance. Experiments were performed to address this seeming paradox and to determine if α-def-1 might provide a means to lower cholesterol and thereby attenuate atherogenesis. We confirmed that exposing ApoE-/- mice to α-def-1 lowers total plasma cholesterol and decreases lesion size. However, lesion size was larger than in mice with total plasma cholesterol lowered to the same extent by inhibiting its adsorption or by ingesting a low-fat diet. Furthermore, α-def-1 levels correlated independently with lesion size in ApoE-/- mice. These studies show that α-def-1 has competing effects on atherogenesis. Although α-def-1 accelerates LDL clearance from plasma, it also stimulates deposition and retention of LDL in the vasculature, which may contribute to development of atherosclerosis in individuals with normal or even low plasma levels of cholesterol. Inhibiting α-def-1 may attenuate the impact of chronic inflammation on atherosclerotic vascular disease.

Freeze-Dried Watermelon Supplementation Has Modest Effects on Bone and Lipid Parameters of Ovariectomized Mice.

This study investigated the effects of two doses of freeze-dried watermelon (WM) on bone and lipid parameters in ovariectomized (OVX) mice, a model of post-menopausal osteoporosis. Three-month-old C57BL/6 female mice (n=46) were sham-operated (SHAM) or OVX and randomly assigned to the control or WM diets for 12 weeks: SHAM-control, OVX-control, OVX+1%, or 10% (wt/wt) freeze-dried WM. All diets were isocaloric and isonitrogenous, and had the same calcium and phosphorus concentrations. Freeze-dried WM supplementation was not able to prevent the decrease in whole body, tibial, and lumbar bone mineral density due to estrogen deficiency. Micro-computed tomography analyses showed that WM was also not able to modulate changes in tibial trabecular and cortical bone microarchitecture due to ovariectomy. However, the lumbar trabecular micro-architecture analyses revealed that the WM-10% group had a similar connectivity density, trabecular number, trabecular separation, and structure model index as the SHAM group. Supplementation with 10% WM reduced plasma cholesterol and total liver lipids to the level of the SHAM group but was still similar to that of the OVX-control group. Supplementation with 10% WM increased liver catalase (CAT) mRNA levels but had no effects on mRNA levels of glutathione peroxidase (GPX) and the pro-inflammatory cytokine interleukin-6. There were no differences in plasma activity of the antioxidant enzymes GPX and CAT between all treatment groups. Our findings demonstrate some positive effects of watermelon for modulating lipids and attenuating lumbar vertebral bone loss arising from ovarian hormone deficiency.

Productive performance, lipid profile and caecum microbial counts of growing rabbits treated with humic acid.

The aim of the present study was to evaluate the effect of a humic acid (HA)-supplemented diet on productive performance and some physiological parameters of growing rabbits. A total of 80 weaned V-line rabbits at an age of 4weeks were randomly divided into four groups. Rabbits of groups 2, 3 and 4 were fed diet containing 35 (HA35), 70 (HA70) and 105 (HA105) mg Humic acid/kg diet while the first group served as control (HA0). Body weight gain was positively affected by HA treatment. HA105 rabbits had the improved feed conversion value. HA treatments had significantly reduced plasma cholesterol concentration and significant increased red blood cells, white blood cells count and plasma high-density lipoprotein concentrations. However, serum aspartate amino transferase and alanine amino transferase activities, creatinine and the apparent nutrients digestibility values were not affected by HA treatments. Organic matter digestibility of all HA-treated groups significantly increased compared with HA0. At 63days of age (after 35days of treatment), caecum microbial counts decreased (total bacteria and Escherichia coli) with HA treatments. Generally HA could be considered as a biological as growth promoter feed additive alternative to antibiotics.

Mediterranean diet intervention in overweight and obese subjects lowers plasma cholesterol and causes changes in the gut microbiome and metabolome independently of energy intake

ObjectivesThis study aimed to explore the effects of an isocaloric Mediterranean diet (MD) intervention on metabolic health, gut microbiome and systemic metabolome in subjects with lifestyle risk factors for metabolic...

Statin-induced myopathic changes in primary human muscle cells and reversal by a prostaglandin F2 alpha analogue

Statin-related muscle side effects are a constant healthcare problem since patient compliance is dependent on side effects. Statins reduce plasma cholesterol levels and can prevent secondary cardiovascular diseases. Although statin-induced muscle damage has been studied, preventive or curative therapies are yet to be reported. We exposed primary human muscle cell populations (n = 22) to a lipophilic (simvastatin) and a hydrophilic (rosuvastatin) statin and analyzed their expressome. Data and pathway analyses included GOrilla, Reactome and DAVID. We measured mevalonate intracellularly and analyzed eicosanoid profiles secreted by human muscle cells. Functional assays included proliferation and differentiation quantification. More than 1800 transcripts and 900 proteins were differentially expressed after exposure to statins. Simvastatin had a stronger effect on the expressome than rosuvastatin, but both statins influenced cholesterol biosynthesis, fatty acid metabolism, eicosanoid synthesis, proliferation, and differentiation of human muscle cells. Cultured human muscle cells secreted ω-3 and ω-6 derived eicosanoids and prostaglandins. The ω-6 derived metabolites were found at higher levels secreted from simvastatin-treated primary human muscle cells. Eicosanoids rescued muscle cell differentiation. Our data suggest a new aspect on the role of skeletal muscle in cholesterol metabolism. For clinical practice, the addition of omega-n fatty acids might be suitable to prevent or treat statin-myopathy.

Deficiency of T-type voltage-gated calcium channels results in attenuated weight gain and improved endothelium-dependent dilatation of resistance vessels induced by a high-fat diet in mice.

The deletion of T-type Cav3.1 channels may reduce high-fat diet (HFD)-induced weight gain, which correlates positively with obesity and endothelial dysfunction. Therefore, experiments were designed to study the involvement of T-type Cav3.1 channels in HFD-induced endothelial dysfunction in mice. Wildtype (WT) and Cav3.1-/- mice were fed either a normal diet (ND) or an HFD for 8weeks. Body composition was assessed, and thoracic aortae and mesenteric arteries were harvested for myography to assess endothelium-dependent responses. Changes in intracellular calcium were measured by fluorescence imaging, and behavior was assessed with the open-field test. Cav3.1-/- mice had attenuated HFD-induced weight gain and lower total fat mass compared with WT mice. Cav3.1-/- mice on an HFD had reduced plasma cholesterol levels compared with WT mice on the same diet. Increased feeding efficiency, independent of food intake, was observed in WT mice on an HFD compared with an ND, but no difference in feeding efficiency between diets was observed for Cav3.1-/- mice. Nitric oxide-dependent dilatation was increased in mesenteric arteries of Cav3.1-/- mice compared with WT mice on an HFD, with no difference observed in aortae. No differences in mouse locomotor activity were observed between the experimental groups. Mice on an HFD lacking T-type channels have reduced weight gain, lower total cholesterol levels, and increased dilatation of resistance vessels compared with WT mice on an HFD, suggesting that Cav3.1 deletion protects against endothelial dysfunction in resistance vessels but not in large conduit vessels.

IgE Contributes to Atherosclerosis and Obesity by Affecting Macrophage Polarization, Macrophage Protein Network, and Foam Cell Formation

By binding to its high-affinity receptor FcεR1, IgE activates mast cells, macrophages, and other inflammatory and vascular cells. Recent studies support an essential role of IgE in cardiometabolic diseases. Plasma IgE level is an independent predictor of human coronary heart disease. Yet, a direct role of IgE and its mechanisms in cardiometabolic diseases remain incompletely understood. Approach and Results: Using atherosclerosis prone Apoe-/- mice and IgE-deficient Ige-/- mice, we demonstrated that IgE deficiency reduced atherosclerosis lesion burden, lesion lipid deposition, smooth muscle cell and endothelial cell contents, chemokine MCP (monocyte chemoattractant protein)-1 expression and macrophage accumulation. IgE deficiency also reduced bodyweight gain and increased glucose and insulin sensitivities with significantly reduced plasma cholesterol, triglyceride, insulin, and inflammatory cytokines and chemokines, including IL (interleukin)-6, IFN (interferon)-γ, and MCP-1. From atherosclerotic lesions and peritoneal macrophages from Apoe-/-Ige-/- mice that consumed an atherogenic diet, we detected reduced expression of M1 macrophage markers (CD68, MCP-1, TNF [tumor necrosis factor]-α, IL-6, and iNOS [inducible nitric oxide synthase]) but increased expression of M2 macrophage markers (Arg [arginase]-1 and IL-10) and macrophage-sterol-responsive-network molecules (complement C3, lipoprotein lipase, LDLR [low-density lipoprotein receptor]-related protein 1, and TFR [transferrin]) that suppress macrophage foam cell formation. These IgE activities can be reproduced in bone marrow-derived macrophages from wild-type mice, but muted in cells from FcεR1-deficient mice, or blocked by anti-IgE antibody or complement C3 deficiency. IgE deficiency protects mice from diet-induced atherosclerosis, obesity, glucose tolerance, and insulin resistance by regulating macrophage polarization, macrophage-sterol-responsive-network gene expression, and foam cell formation.

Wild Melon Seed Oil Reduces Plasma Cholesterol and Modulates Gut Microbiota in Hypercholesterolemic Hamsters.

Wild melon (Cucumis melo var. agrestis) seed oil (CO) contains 71.3% polyunsaturated fatty acids. The present study investigated the effects of CO on blood cholesterol and gut microbiota. Hamsters (n = 32) were randomly divided into four groups and given one of four diets, namely noncholesterol diet (NCD), high-cholesterol diet containing 0.1% cholesterol (HCD), HCD containing 4.75% CO (COL), and HCD containing 9.5% CO (COH) for 6 weeks. CO supplementation at 9.5% in the diet reduced plasma cholesterol by 24% and enhanced the excretion of fecal bile acids by 150%. CO supplementation upregulated the gene expression of hepatic cholesterol 7α-hydroxylase (CYP7A1). In addition, supplementation of CO in the diet remarkably increased the production of fecal short-chain fatty acids and favorably altered the relative abundances of Eubacteriaceae, Clostridiales_vadinBB60_group, Ruminococcaceae, Streptococcaceae, and Desulfovibrionaceae at a family level. It was concluded that CO could reduce plasma cholesterol via promoting the excretion of fecal acidic sterols and modulating gut microbiota.

Natural cocoa improves birth weight and viability of rabbit pups born to hypercholesterolemic mothers

BackgroundMaternal nutrition affects fetal growth and development in humans and animals. Low birth weight can be caused by maternal hypercholesterolemia and is associated with increased risk of cardiovascular and other metabolic diseases later in adult life. Cocoa powder is rich in flavonoids and reduces plasma cholesterol levels. The study investigated the effect of hypercholesterolemia and natural cocoa intake during pregnancy on the birth weight and viability of rabbit pups. MethodsHypercholesterolemic female New Zealand White rabbits were crossed with normocholesterolemic males and randomly grouped into 2 (n = 4 each). One group (HCC) received natural cocoa powder in their water in addition to high cholesterol diet during pregnancy, whereas the other (HC) received only water and high cholesterol diet. Litter size, birth weight and viability of pups were assessed and compared to a control group (NC) fed normal rabbit chow (n = 2). ResultsAverage litter sizes of hypercholesterolemic rabbits (HC and HCC groups) were 3, whereas that of control group, NC was 5. Mean birth weight of pups was significantly lower in offspring of HC (42.73 g, SD 8.47) and HCC (50.0 g, SD 3.54) as compared to NC (73.0 g, SD 5.37). Mortality of offspring was highest in HC group (58.3%) as compared to 50% in HCC. ConclusionsMaternal hypercholesterolemia during pregnancy reduces litter size, birth weight and viability of offspring in rabbits and these deleterious effects may be minimized by regular intake of natural cocoa. Although further studies in humans need to be conducted, the results of this study suggest the need to monitor maternal cholesterol levels during pregnancy and the effects on pregnancy outcomes and health of offspring later in life.

Myeloid atg5 deletion impairs n-3 PUFA-mediated atheroprotection

Background and aimsDietary long-chain (≥20 carbons) n-3 polyunsaturated fatty acids (PUFAs) reduce atherosclerosis and enhance macrophage autophagy activation. How macrophage autophagy impacts atherosclerotic progression, particularly when comparing dietary n-3 PUFA supplementation vs. saturated fat feeding, is unknown. MethodsWe generated myeloid-specific autophagy-deficient and control mice in the Ldlr−/− background by transplanting bone marrow from myeloid-specific autophagy-related (atg) 5 knockout mice and wild type controls into irradiated Ldlr−/− recipients. After 7 weeks for recovery from radiation, mice were fed an atherogenic diet containing 0.2% cholesterol and 20% calories as palm oil (PO diet), or 10% calories as PO plus 10% calories as fish oil (FO diet) for 16 weeks. ResultsCompared to PO, FO significantly reduced plasma cholesterol, triglyceride, hepatic neutral lipid, and aortic caspase-1 cleavage, but increased aortic efferocytosis, leading to attenuated atherosclerosis in Ldlr−/− mice receiving wild type bone marrow. Myeloid atg5 deletion had little impact on plasma lipid concentrations and hepatic neutral lipid content, regardless of diet. Myeloid atg5 deletion increased aortic caspase-1 cleavage, decreased aortic efferocytosis and worsened atherosclerosis only in the FO-fed Ldlr−/− mice. ConclusionsDeficient myeloid autophagy significantly attenuated FO-induced atheroprotection, suggesting that dietary n-3 PUFAs reduce atherosclerosis, in part, by activation of macrophage autophagy.

Effects of dietary hawthorn extracts supplementation on lipid metabolism, skin coloration and gut health of golden pompano (Trachinotus ovatus)

Hawthorn fruit has long been used as a functional food in China due to its effects of increasing appetite, promoting digestion and protecting the gastrointestinal tract. The present study was conducted to assess the impact of dietary hawthorn extract (HTE) supplementation on plasma biochemical indices, proximate body composition, skin coloration, intestinal morphology and changes in mRNA expression of immune-related genes and tight junction proteins genes in the intestine of golden pompano. Basal diets supplemented with HTE at 0, 0.50, 1.00, 2.00, 4.00 and 10.00 g kg−1 were fed to golden pompano for eight weeks. The study showed dietary HTE supplementation had hypolipidemic effects by reducing plasma cholesterol, triglyceride and low density lipoprotein content and improved skin coloration by increasing yellowness values of the ventral skin color of golden pompano. Meanwhile, dietary supplementation of 0.50 and 1.00 g kg−1 HTE could improve gut morphology by increasing villus length, villus width and muscle thickness, and enhance barrier function by increasing tight junction protein genes mRNA levels. However, dietary 10.00 g kg−1 HTE supplementation not only caused damage to intestinal morphology and barrier function, but also induced oxidative stress and inflammatory response. Our study demonstrated that dietary 0.50 and 1.00 g kg−1 HTE supplementation was beneficial for skin coloration and intestinal health of golden pompano.

Behavioral and physiological assessments to evaluate the effect of Acacia senegal and Acacia seyal in albino mice

Background: Acacia senegal and Acacia seyal (family Leguminosae) are the sources of Gum Arabic that is widely used in food-processing and pharmaceutical industries. The neuropharmacological activities of A. senegal and A. seyal remain unexplored. Objective: The objective of the study was to investigate the neuropharmacological activities of A. senegal and A. seyal. Materials and Methods: Behavior, variations in selected blood parameters, acetylcholinesterase (AChE) activity, and lipid peroxidation level were studied in normal Albino mice that received A. senegal and A. seyal extracts. Results: The results revealed a significant decrease in the body weight of mice after the treatment with the extract of A. senegal and A. seyal compared to the control group. The locomotor activity in the treated mice decreased as well. In forced swimming test (FST), the treated mice showed a marked reduction in immobility respective to increase in the dose. The anxiety reflex test (FRT) revealed an increase in the percentage of time spent in the open arms of the maze. The treatment resulted in a notable decrease in motion balance and function. The active avoidance test revealed a dose-dependent reduction in avoidance. The study provided the evidence that A. senegal and A. seyal contributed to reduction in plasma cholesterol and glucose levels in treated mice, with no marked variations in hemoglobin level. Estimation of AChE resulted in minor decline in the activity in the treated group of mice. A. senegal was safer than A. seyal, but exerted toxicity at high dose. Conclusions: Low doses of A. senegal have the potential to be used for the development of the treatment for neurological disorders.

Vinegars but not acetic acid are effective in reducing plasma cholesterol in hamsters fed a high-cholesterol diet

The present study compares the effect of two types of vinegars, Balsamic vinegar of Modena (BV) and Chinese Shanxi vinegar (SV), with acetic acid on plasma cholesterol using hamsters as a model. Hamsters (n = 40) were divided into five groups (n = 8 each) with two control groups being fed a low-cholesterol diet (LCD) or a high-cholesterol diet containing 0.2% cholesterol (HCD). The three experimental groups were given a HCD diet and gavaged with 8 ml of BV, SV, and acetic acid solution (AC) per kg body weight, respectively. Acetic acid in BV, SV, and AC solutions was adjusted with water to be 20 mg ml-1. The whole experiment lasted for 9 weeks. Plasma total cholesterol (TC) in BV and SV groups but not in the AC group was reduced by 17% and 20%, respectively, compared with that in HCD hamsters. BV and SV significantly reduced cholesterol in the liver and increased the fecal excretion of neutral sterols and bile acids. Real-time PCR analysis demonstrated that BV and SV significantly up-regulated the mRNA of cholesterol 7 alpha-hydroxylase (CYP7A1) in the liver. In conclusion, BV and SV but not AC were effective in reducing plasma TC and non-HDL-C concentrations at least in hypercholesterolemic hamsters.

Statin use and the risk of renal cell carcinoma: national cohort study

Statins are a therapeutic drug with reducing plasma cholesterol levels and have been linked with potential antitumor effects. However, epidemiological studies on statin use and renal cell carcinoma (RCC) risk...

Plasma Cholesterol-Lowering Activity of Soybean Germ Phytosterols.

Soybean germ phytosterols (SGP) largely exist in soybean germ oil. Our previous study demonstrated that soybean germ oil was effective in reducing plasma cholesterol. However, it remains unknown if its phytosterols are the active ingredients responsible for the plasma cholesterol-lowering activity. The present study aimed to test the effect of SGP on plasma cholesterol and to investigate its associated underlying mechanisms using hamsters as animal model. Male hamsters (n = 40) were randomly divided into five groups (n = 8/group) and fed one of the five diets: a non-cholesterol diet (NCD), a high cholesterol diet (HCD), a HCD diet containing 0.5% cholestyramine (PC), and two HCD diets containing 0.1% (LP) and 0.2% (HP) SGP, respectively, for six weeks. Results showed that SPG reduced plasma cholesterol level in a dose-dependent manner, whereas it dose-dependently increased the excretion of both fecal neutral and acidic sterols. SGP was also effective in displacing cholesterol from micelles. It was concluded that SGP possessed hypocholesterolemic activity, likely by inhibiting cholesterol absorption in the intestine and promoting fecal sterol excretion.

The Effects of Administration of Vitamin D, Infliximab, and Leflunomide on Testosterone Concentrations in Rats under Atorvastatin Therapy.

Statins inhibit the 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase enzyme and thus reduce plasma cholesterol levels. Although decreased cholesterol level is the main target of anti-lipidemic drugs, cholesterol has an important role in the synthesis of lipid-based hormones such as testosterone. In this study, the alterations in serum testosterone levels were examined in rats under atorvastatin therapy and their responses to vitamin D, infliximab, and leflunomide supplementation were evaluated. Wistar rats were treated with atorvastatin (100 mg/kg) for 21 days to induce inhibition of the HMG-CoA reductase enzyme activity. Following statin therapy, rats received vitamin D (0.2 μg/kg/day) orally for 15 days, infliximab (7 mg/kg/day) intraperitoneally in two doses, or leflunomide (10 mg/kg/day) orally in two doses. Subsequently, the alterations in serum testosterone levels were measured by ELISA. Atorvastatin led to a decrease in the testosterone level compared to the vehicle group. Administration of vitamin D, infliximab, and leflunomide under HMG-CoA inhibition insignificantly increased the testosterone level compared to the atorvastatin control group. Furthermore, it appears that rats under statin administration respond better to treatment with leflunomide by achieving a greater induction in testosterone levels than with vitamin D or infliximab. Our data provide evidence that administration of vitamin D, infliximab, and leflunomide in rats under atorvastatin treatment may ameliorate the serum testosterone levels.

Plasma oxyphytosterol concentrations are not associated with CVD status in Framingham Offspring Study participants

Dietary plant sterols, such as campesterol and sitosterol, reduce plasma cholesterol concentrations, but any relationship to plaque development and CVD remains unclear. Some epidemiologic studies have suggested that elevated plasma plant sterol concentrations are atherogenic, including the Framingham Offspring Study that identified a positive association between plant sterol concentrations and CVD status. We hypothesized that this suggested atherogenicity relates to the oxidation status of plant sterols (i.e., concentrations of plasma oxyphytosterols). Therefore, in the Framingham Offspring Study cohort, we measured plasma oxyphytosterol concentrations in 144 patients with documented CVD and/or more than 50% carotid stenosis and 383 matched controls. We analyzed plasma oxyphytosterol concentrations by GC/MS/MS and performed conditional logistic regression analysis to determine associations between plasma plant sterol or oxyphytosterol concentrations and CVD status. We found that higher total cholesterol (TC)-standardized campesterol concentrations [odds ratio (OR): 2.36; 95% CI: 1.60, 3.50] and higher sitosterol concentrations (OR: 1.47; 95% CI: 1.09, 1.97) were significantly associated with increased CVD risk, as in the earlier study. However, the sum of absolute oxyphytosterol concentrations (OR: 0.99; 95% CI: 0.81, 1.21) and the sum of TC-standardized oxyphytosterol concentrations (OR: 0.98; 95% CI: 0.80, 1.19) were not associated with an increased CVD risk. Results were comparable for individual absolute and TC-standardized oxycampesterol and oxysitosterol concentrations. Plasma nonoxidized TC-standardized sitosterol and campesterol concentrations showed weak or no correlations with oxyphytosterol concentrations, while all individual plasma concentrations of oxyphytosterol correlated with each other. In conclusion, circulating plasma oxyphytosterols are not associated with CVD risk in the Framingham Offspring Study.

GPR146 Deficiency Protects against Hypercholesterolemia and Atherosclerosis

Although human genetic studies have implicated many susceptible genes associated with plasma lipid levels, their physiological and molecular functions are not fully characterized. Here we demonstrate that orphan G protein-coupled receptor 146 (GPR146) promotes activity of hepatic sterol regulatory element binding protein 2 (SREBP2) through activation of the extracellular signal-regulated kinase (ERK) signaling pathway, thereby regulating hepatic very low-density lipoprotein (VLDL) secretion, and subsequently circulating low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) levels. Remarkably, GPR146 deficiency reduces plasma cholesterol levels substantially in both wild-type and LDL receptor (LDLR)-deficient mice. Finally, aortic atherosclerotic lesions are reduced by 90% and 70%, respectively, in male and female LDLR-deficient mice upon GPR146 depletion. Taken together, these findings outline a regulatory role for the GPR146/ERK axis in systemic cholesterol metabolism and suggest that GPR146 inhibition could be an effective strategy to reduce plasma cholesterol levels and atherosclerosis.

Metabolic and gut microbiome changes following GLP-1 or dual GLP-1/GLP-2 receptor agonist treatment in diet-induced obese mice

Enteroendocrine L-cell derived peptide hormones, notably glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2), have become important targets in the treatment of type 2 diabetes, obesity and intestinal diseases. As gut microbial imbalances and maladaptive host responses have been implicated in the pathology of obesity and diabetes, this study aimed to determine the effects of pharmacologically stimulated GLP-1 and GLP-2 receptor function on the gut microbiome composition in diet-induced obese (DIO) mice. DIO mice received treatment with a selective GLP-1 receptor agonist (liraglutide, 0.2 mg/kg, BID) or dual GLP-1/GLP-2 receptor agonist (GUB09–145, 0.04 mg/kg, BID) for 4 weeks. Both compounds suppressed caloric intake, promoted a marked weight loss, improved glucose tolerance and reduced plasma cholesterol levels. 16S rDNA sequencing and deep-sequencing shotgun metagenomics was applied for comprehensive within-subject profiling of changes in gut microbiome signatures. Compared to baseline, DIO mice assumed phylogenetically similar gut bacterial compositional changes following liraglutide and GUB09-145 treatment, characterized by discrete shifts in low-abundant species and related bacterial metabolic pathways. The microbiome alterations may potentially associate to the converging biological actions of GLP-1 and GLP-2 receptor signaling on caloric intake, glucose metabolism and lipid handling.

Preventive Effect of Polyunsaturated Fatty Acid and Vitamin E in Rice Bran Oil on Lifestyle-Related Diseases.

The dietary fat intake of Japanese is thought to be more appropriate than in Western countries; however there is a range of differences of individuals in the amounts of fat intake and n-6/n-3 ratio. Therefore, it is important what kind of vegetable oils are used for cooking in order to consider the total balance of fat intake. Rice bran oil (RBO) is expected to reduce plasma cholesterol and be useful for prevention of cardiovascular disease because it contains several effective ingredients. RBO is rich in linoleic and oleic acid. RBO contains γ-oryzanol, which is well known to reduce plasma cholesterol levels. Furthermore, it contains tocotrienols, which are analogs of vitamin E, reported to have unique bioactivity different from that of α-tocopherol. The biological function of these components and their potential to prevent Japanese lifestyle-related diseases are discussed.