Effect of (poly)phenol-rich 'Daux Belan' apple supplementation on diet-induced obesity and glucose intolerance in C57BL/6NCrl mice.

Obesity is a state of metabolic dysfunction that can lead to dyslipidemia and impaired glucose homeostasis. Apple polyphenols have been shown to ameliorate dyslipidemia/metabolic dysfunction in humans. The influence of apple (poly)phenols on energy metabolism in high-fat (HF) diet-induced obese mice remains controversial. This study examined the effect of dietary supplementation of (poly)phenol-rich 'Daux Belan' apple (DB; 6.2 mg gallic acid equivalence (GAE)/mouse/day; 0.15% (poly)phenol) in the form of freeze-dried powder on glucose and lipid metabolism in male HF-fed C57BL/6NCrl mice, in comparison to low-(poly)phenol-containing 'Zestar' apple (Z; 0.4 mg GAE/mouse/day). Obesity, glucose intolerance, hypertriglyceridemia, and hepatic lipid vacuolation were induced by HF feeding while circulating cholesterol levels remained unchanged. DB apple supplementation did not protect against HF-induced body weight gain, hyperglycemia, hepatic triglyceride level elevation, and hepatic lipid vacuolation at the tested dosage. Future studies should be conducted with increased DB dosage and employ apple (poly)phenols supplemented in the form of extracts or sugar-free powder.

Myrtle Berries Seeds Prevent Dyslipidemia, Inflammation, and Excessive Cardiac Reactive Oxygen Species Production in Response to High-Fat Diet-Induced Obesity.

Anthocyanins are the major polyphenols in myrtle berries seeds aqueous extract (MBSAE). This study investigates the protective potentials of MBSAE against obesity lipotoxicity and inflammation induced by a high-fat diet (HFD). It also describes the underlying mechanisms involved in its protective effects, with special attention to myocardial reactive oxygen species (ROS) production. Male Wistar rats were fed HFD for 6 weeks to induce obesity. MBSAE (100 mg/kg, b.w., p.o.) was orally administered to HFD-fed rats. Anti-obesity effects were triggered by the inhibitory action of the MBSAE against the weights of the body, its relative heart and the total abdominal fat. Treatment with MBSAE also restored the lipid profile to baseline compared with the HFD rats and lowered also the white blood cells count, including neutrophils, lymphocytes, and basophils number as well as cytokines (tumor necrosis factor-α, interleukin [IL]-6, and IL-1ß) levels in the rats serum, thus improving the tissue inflammatory status associated with obesity. Exposure of rats to HFD during 6 weeks induces a myocardial oxidative stress as assessed by deleterious effects on lipoperoxidation state, antioxidant enzyme (SOD, CAT, and GPx) activities as well as sulfhydryl groups and GSH rates. Of importance, our study shows also that HFD provokes a heart ROS (H2O2, OH•, and O2•-) overload. Of interest, all these oxidative heart disturbances were clearly ended by MBSAE treatment. Therefore, consumption of MBSAE as a natural extract may be a potential therapeutic strategy to treat obesity-associated diseases.

Nutraceutical Approaches to Dyslipidaemia: The Main Formulative Issues Preventing Efficacy.

Currently, the nutraceutical approach to treat dyslipidaemia is increasing in use, and in many cases is used by physicians as the first choice in the treatment of patients with borderline values. Nutraceuticals represent an excellent opportunity to treat the preliminary conditions not yet showing the pathological signs of dyslipidaemia. Their general safety, the patient's confidence, the convincing proof of efficacy and the reasonable costs prompted the market of new preparations. Despite this premise, many nutraceutical products are poorly formulated and do not meet the minimum requirements to ensure efficacy in normalizing blood lipid profiles, promoting cardiovascular protection, and normalizing disorders of glycemic metabolism. In this context, bioaccessibility and bioavailability of the active compounds is a crucial issue. Little attention is paid to the proper formulations needed to improve the overall bioavailability of the active molecules. According to these data, many products prove to be insufficient to ensure full enteric absorption. The present review analysed the literature in the field of nutraceuticals for the treatment of dyslipidemia, focusing on resveratrol, red yeast rice, berberine, and plant sterols, which are among the nutraceuticals with the greatest formulation problems, highlighting bioavailability and the most suitable formulations.

Dietary supplementation with Tolypocladium sinense mycelium prevents dyslipidemia inflammation in high fat diet mice by modulation of gut microbiota in mice.

Obesity is a risk factor for many serious health problems, associated with inflammation, hyperlipidemia, and gut dysbiosis. Prevention of obesity is especially important for human health. Tolypocladium sinense is one of the fungi isolated from Chinese caterpillar fungus, which is a traditional Chinese medicine with putative gut microbiota modulation effects. Here, we established a high-fat diet (HFD)-induced hyperlipidemia mice model, which was supplemented with lyophilized T. sinense mycelium (TSP) daily to evaluate its anti-obesity effects. The results indicated that TSP supplementation can effectively alleviate the inflammatory response and oxidative stress levels caused by obesity. TSP significantly prevented obesity and suppressed dyslipidemia by regulating the expression of lipid metabolism genes in the liver. TSP is also effective in preventing the HFD-induced decline in short-chain fatty acid (SCFA) content. Gut microbiota profiling showed that TSP supplementation reversed HFD diet-induced bacterial abundance and also altered the metabolic pathways of functional microorganisms, as revealed by KEGG analysis. It is noteworthy that, correlation analysis reveals the up-regulated gut microbiota (Lactobacillus and Prevotella_9) are closely correlated with lipid metabolism parameters, gene expression of liver lipid metabolism and inflammatory. Additionally, the role of TSP in the regulation of lipid metabolism was reconfirmed by fecal microbiota transplantation. To sum up, our results provide the evidence that TSP may be used as prebiotic agents to prevent obesity by altering the gut microbiota, alleviating the inflammatory response and regulating gene expression of liver lipid metabolism.

Phytonutrients of bilberry fruit and saskatoon berry in the prevention and treatment of dyslipidemia.

The epidemiologic studies from the recent years indicate that high consumption of foods rich in bioactive compounds has a positive effect on human health and could diminish the risk of numerous diseases, such as cancer, heart disease, stroke, Alzheimer's disease, diabetes, cataracts, and even diseases related to age. From all species of fruit, definitely consumption of berries due to its high content of bioactive constituents prevents the risk of cardiovascular disease, oxidative stress and diabetes. The primary phenolic compounds in berries are flavonoids, particularly the anthocyanins. They have potential preventative and therapeutic effects on many diseases such as cancers, inflammation and cardiovascular diseases, obesity, neurodegenerative pathologies, and muscular degeneration. Bilberry fruits have been an important part of local diets in many countries, including Slovakia. They are valued for their pleasant taste and aroma and are often processed into jams, preserves, juices, and alcoholic beverages. In the last two decades, the Saskatoon berry has been cultivated in many parts of the world for its suitability for various food products and due to its high content of nutrients and polyphenols. Cardiovascular disease (CVD) remains the world's leading cause of morbidity and mortality. Dyslipidemia, which results from one or more abnormalities of blood lipids metabolism, remains a major key factor for progression of CVD and leads to the development of atherosclerotic plaques. The aim of this review is to compare and summarize the research evidence on the potential of bilberries and saskatoon berries with an emphasis on recent studies in humans in improving cardiovascular risk factors especially dyslipidemia.

Metabolomics Analysis Reveals the Effects of Compound Fuzhuan Brick Tea (CFBT) on Regulating Dyslipidemia and Metabolic Disorders in Mice Induced by High-Fat Diet.

BACKGROUND: It is well known that obesity induced by high-fat diet (HFD) poses a serious threat to people's health. Fuzhuan brick tea, one of the most popular beverages, is reported to possess a significant effect on regulating lipid metabolism, attributed to its many bioactive ingredients. However, the efficacy and mechanism of compound Fuzhuan brick tea (CFBT) made from Fuzhuan brick tea and other six Chinese herbal medicines are still not well defined. METHODS: Sixty mice were divided into six groups: normal control group (CK), high-fat model group (NK), positive control group with anti-hyperlipidemic drug (YK), CFBT at low-(FL), medium-(FM) and high-(FH) dosage. Intervening for 30 days, conventional indexes analysis combined with metabolomics were performed to evaluate the changes in biochemical indexes and liver metabolic profiles in mice submitted to HFD. RESULTS: CFBT treatment was able to ameliorate obesity, serum biochemical parameters, antioxidant activity and hepatic steatosis. In addition, significant alterations in the liver tissue metabolic profiles were observed, with most of these associated with inflammation, glucose and lipid metabolism. CONCLUSIONS: This study provides evidence that consumption of CFBT is capable of preventing dyslipidemia, reducing weight gain, restoring liver injury, as well as improving metabolic disorders.

Nutraceuticals for Dyslipidaemia and Glucometabolic Diseases: What the Guidelines Tell Us (and Do Not Tell, Yet).

BACKGROUND: The use of nutraceutical products and functional foods in the cardiovascular and metabolic field is rising in several countries. Preparation and implementation of guidelines are pivotal for translating research-derived knowledge and evidence-based medicine to the clinical practice. Based on these considerations, the aim of this paper is to explore if and how nutraceutical products are discussed by the most recent international guidelines related to cardio-metabolic diseases (dyslipidaemia, obesity, type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) prevention). Some, but not all, guidelines for dyslipidaemia mention nutraceutical products as potential useful options for the treatment of mild dyslipidaemia, but also indicate the low level of evidence associated to their effects on hard endpoints (myocardial infarction, stroke, CVD-related death). In the most recent guidelines on obesity, it is mentioned that no safe and effective dietary supplement nor nutraceutical product is available for the management of weight loss in this condition, and more high-quality studies are necessary in this field. The examined guidelines for T2DM do not mention any specific nutraceutical approach to this disease, nor to milder forms, such as insulin resistance and pre-diabetes. CONCLUSIONS: The focus on nutraceutical products in the main international guidelines for cardio-metabolic disease management remains limited. Since robust scientific evidence is the background of useful and effective guidelines, the implementation of high-quality clinical research is strongly needed in the field of nutraceutical products for cardio-metabolic diseases.

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.

The effect of calcium supplement intake on lipid profile: a systematic review and meta-analysis of randomized controlled clinical trials.

Despite the potential role of dietary calcium in fat excretion, the favorable effects of calcium supplements on lipid profile remains inconclusive. The current study aimed to review the effect of calcium supplement intake on lipid profile in randomized controlled clinical trials (RCTs). This systematic review and meta-analysis was conducted in PubMed, Scopus, Embase, and Central. RCTs which assessed the effects of calcium supplementation on lipid profile were included. All outcomes were recorded as continuous variables, and the effect size was measured. We classified studies according to dose of supplement, study duration, and dyslipidemia. Calcium supplement intake was associated with a significant reduction in low density lipoprotein cholesterol (LDL-C) level (WMD:-0.08; 95%CI:-0.16,-0.01)(mmol/l), especially with intakes of at least 1000 mg/day (WMD:-0.13; 95%CI:-0.23,-0.03)(mmol/l), with intakes of at least 12 weeks (WMD:-0.08; 95%CI: -0.16,-0.00)(mmol/l), and in individuals without dyslipidemia (WMD:-0.15; 95%CI:-0.26,-0.04)(mmol/l). Also, in another subgroup analysis, consumption of less than 1000 mg/day calcium supplement caused a significant increase in Total Cholesterol (TC) level (WMD: 0.24; 95%CI: 0.05,0.42) (mmol/l). In other blood lipids or study subgroups we observed no significant effect. We concluded that calcium supplements had a favorable effect on LDL-C level, especially in individuals without dyslipidemia, higher calcium intakes, and longer period of consumption.

Avaliação de desfecho de pacientes com dislipidemia em uso de terapia tripla combinada: sinvastatina, ezetimiba e ômega 3 / Outcome evaluation of patients with dyslipidemia using combined triple therapy: simvastatin, ezetimibe and omega 3

Introdução: As doenças crônicas configuram importante problema de saúde coletiva no Brasil, principalmente hipertensão arterial, doenças cardiovasculares, acidentes vasculares cerebrais e diabetes, sendo um dos principais fatores de risco, as dislipidemias. Numerosos estudos clínicos mundiais estabeleceram a associação entre dislipidemia e aumento da mortalidade. O Brasil acompanha este fenômeno internacional. Observa-se uma pobre cultura sanitária sobre o problema, bem como hábitos de vida da população e pouca informação sobre o tema. Considerando este cenário, o presente estudo avaliou a melhoria do perfil lipídico dos pacientes atendidos no Ambulatório de Clínica Médica do Hospital do Servidor Público Municipal em uso de terapia tripla combinada (sinvastatina, ezetimiba e ômega 3). Resultados: apresentou-se uma grande redução do perfil lipídico dos pacientes analisados. A síndrome metabólica foi a comorbidade a qual apresentou a queda mais expressiva do perfil lipídico, chegando ao valor de redução do LDL em 43,99%, colesterol total 33,06% e triglicerídeos 38,77%. Discussão: foi visto uma redução no perfil lipídico de forma significativa, levantando a possibilidade que a terapia tripla pode ter efeitos sinérgicos na redução do colesterol e triglicerídeos. Conclusão: administração da terapia tripla combinada com sinvastatina 40mg, ezetimiba 10mg e ômega 3 (EPA e DHA 900mg ­ 1000mg), não induziu algum efeito tóxico ou evento cardiovascular, assim como efeito adverso novo. Além disso, demonstrou uma redução significante do perfil lipídico. Palavras-chave: Dislipidemia. Estatinas. Doenças crônicas. Promoção da saúde.

The protective mechanism of a debranched corn starch/konjac glucomannan composite against dyslipidemia and gut microbiota in high-fat-diet induced type 2 diabetes.

This study aimed to explore the protection mechanism of a debranched corn starch/konjac glucomannan (DCSK) composite against type 2 diabetes (T2D) related to dyslipidemia and gut microbiota in mice fed on a high-fat diet (HFD). The results showed that the consumption of DCSK led to a significant improvement in the biochemical parameters and physiological indices associated with T2D in the HFD group, including the decrease in blood glucose, triglyceride, total cholesterol, and high-density lipoprotein cholesterol levels, as well as the suppression of the oxidative stress of the liver and kidneys. Furthermore, the health of the intestinal microbiota in the HFD-fed mice was altered dramatically after DCSK consumption. Metabolomics revealed 13 differential metabolites strongly linked to DCSK intervention, and DCSK supplementation regulated amino acid metabolism, nucleotide metabolism, and lipid metabolism. These findings demonstrated that DCSK has an outstanding ability to improve hyperglycemia, hyperlipidemia, and gut microbiota associated with T2D.

Beneficial impacts of fermented celery (Apium graveolens L.) juice on obesity prevention and gut microbiota modulation in high-fat diet fed mice.

Metabolic syndrome caused obesity has long been recognized as a risk of health. Celery and celery extracts have various medicinal properties, such as anti-diabetes and anti-inflammatory properties and blood glucose and serum lipid reduction. However, the effect of probiotic fermentation on celery juice and the association between fermented celery juice (FCJ) and obesity were unclear. This study aimed to evaluate the beneficial effects of FCJ on high-fat diet (HFD) induced obesity and related metabolic syndromes. C57BL/6 mice were randomly divided into six groups (n = 15 per group) fed either a normal diet (ND) or HFD with or without CJ/FCJ (10 g kg-1 day-1) by oral gavage for 12 weeks. Here we demonstrated that the probiotic fermentation of celery juice (CJ) could enhance the active ingredients in celery, such as total polyphenols, flavonoids, vitamin C and SOD. Compared to the slight improvement induced by CJ ingestion, FCJ intake significantly inhibited body weight gain, prevented dyslipidemia and hyperglycemia, and suppressed visceral fat accumulation. Furthermore, 16S rRNA sequencing analysis revealed that FCJ intake altered the composition of gut microbiota, increasing the ratio of Firmicutes/Bacteroidetes and the relative abundance of beneficial bacteria (Lactobacillus, Ruminococcaceae_UCG-014, Faecalibaculum and Blautia), and decreasing the relative abundance of harmful bacteria (Alloprevotella and Helicobacter). These findings suggest that FCJ can prevent HFD-induced obesity and become a novel gut microbiota modulator to prevent HFD-induced gut dysbiosis and obesity-related metabolic disorders.

Hepatoprotective effect of Spirulina platensis against carbon tetrachloride-induced liver injury in male rats.

OBJECTIVES: Spirulina platensis (SP) is an edible Cyanobacterium with ethnomedicinal significance. This study aims at evaluating the beneficial effect of SP against carbon tetrachloride (CCl4)-induced liver toxicity in male rats. METHODS: Rats received intraperitoneal injections of CCl4 (2 ml/kg body weight [b.w.] per every other day) for 40 days, alone or in combination with oral treatments of SP (400 mg/kg b.w. per day). KEY FINDINGS: SP attenuated haematological disturbances, serum liver markers, hepatic necrosis and inflammation, and dyslipidemia in CCl4-intoxicated rats. SP also reduced CCl4-induced oxidative stress by increasing the activities of antioxidant enzymes, such as glutathione peroxidase, superoxide dismutase and catalase and glutathione content, and inhibiting lipid peroxidation products and nitric oxide levels in the rat liver. Further investigations revealed that SP counteracted CCl4-induced increased hepatic levels of Ki-67 (a parameter of cell proliferation), interleukin-6, and tumour necrosis factor-alpha and cyclooxygenase-2 messenger RNA expression. Noticeably, the supplementation of SP restored the decrease of proapoptotic p53 protein levels in the liver of rats treated with CCl4. CONCLUSIONS: SP prevented liver damage in CCl4-treated rats via augmentation of antioxidant defense mechanisms and inhibition of inflammatory cytokines/mediators and antiproliferative effects.

Maternal omega-3 fatty acids maintained positive maternal lipids and cytokines profile, and improved pregnancy outcomes of C57BL/6 mice.

Omega (n)-3 polyunsaturated fatty acids (PUFA) are known to regulate lipid metabolism and inflammation; however, the regulation of maternal lipid metabolism and cytokines profile by n-3 PUFA during different gestation stages, and its impact on fetal sustainability is not known. We investigated the effects of maternal diet varying in n-3 PUFA prior to, and during gestation, on maternal metabolic profile, placental inflammatory cytokines, and fetal outcomes. Female C57BL/6 mice were fed either a high, low or very low (9, 3 or 1% w/w n-3 PUFA) diet, containing n-6:n-3 PUFA of 5:1, 20:1 and 40:1, respectively for two weeks before mating, and throughout pregnancy. Animals were sacrificed prior to mating (NP), and during pregnancy at gestation days 6.5, 12.5 and 18.5. Maternal metabolic profile, placental cytokines and fetal outcomes were determined. Our results show for the first time that a maternal diet high in n-3 PUFA prevented dyslipidemia in NP mice, and maintained the expected lipid profile during pregnancy. However, females fed the very low n-3 PUFA diet became hyperlipidemic prior to pregnancy, and carried this profile into pregnancy. Maternal diet high in n-3 PUFA maintained maternal plasma progesterone and placental pro-inflammatory cytokines profile, and sustained fetal numbers throughout pregnancy, while females fed the low and very-low n-3 PUFA diet had fewer fetuses. Our findings demonstrate the importance of maternal diet before, and during pregnancy, to maintain maternal metabolic profile and fetus sustainability. These findings are important when designing dietary strategies to optimize maternal metabolism during pregnancy for successful pregnancy outcome.

Fenofibrate Regulates Visceral Obesity and Nonalcoholic Steatohepatitis in Obese Female Ovariectomized C57BL/6J Mice.

Fibrates, including fenofibrate, are a class of hypolipidemic drugs that activate peroxisome proliferator-activated receptor α (PPARα), which in-turn regulates the expression of lipid and lipoprotein metabolism genes. We investigated whether fenofibrate can reduce visceral obesity and nonalcoholic fatty liver disease via adipose tissue PPARα activation in female ovariectomized (OVX) C57BL/6J mice fed a high-fat diet (HFD), a mouse model of obese postmenopausal women. Fenofibrate reduced body weight gain (-38%, p < 0.05), visceral adipose tissue mass (-46%, p < 0.05), and visceral adipocyte size (-20%, p < 0.05) in HFD-fed obese OVX mice. In addition, plasma levels of alanine aminotransferase and aspartate aminotransferase, as well as free fatty acids, triglycerides, and total cholesterol, were decreased. Fenofibrate also inhibited hepatic lipid accumulation (-69%, p < 0.05) and infiltration of macrophages (-72%, p < 0.05), while concomitantly upregulating the expression of fatty acid ß-oxidation genes targeted by PPARα and decreasing macrophage infiltration and mRNA expression of inflammatory factors in visceral adipose tissue. These results suggest that fenofibrate inhibits visceral obesity, as well as hepatic steatosis and inflammation, in part through visceral adipose tissue PPARα activation in obese female OVX mice.

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.

Effects of dietary n-3 PUFA levels in early life on susceptibility to high-fat-diet-induced metabolic syndrome in adult mice.

The maternal nutritional status during pregnancy and lactation was closely related to the growth and development of the fetus and infants, which had a profound impact on the health of the offspring. N-3 polyunsaturated fatty acid (PUFA) had been proved to have beneficial effects on glucolipid metabolism. However, the effects of dietary different n-3 PUFA levels for mother during pregnancy and lactation on susceptibility to high-fat-diet-induced metabolic syndrome for offspring in adulthood are still unclear. The maternal mice were fed with control, n-3 PUFA-deficient or fish oil-contained n-3 PUFA-rich diets during pregnancy and lactation, and the weaned offspring were fed with high-fat or low-fat diet for 13 weeks, then were subjected to oral glucose tolerance tests. The results showed that dietary n-3 PUFA-deficiency in early life could aggravate the high-fat-diet-induced glucolipid metabolism disorders, including glucose intolerance, insulin resistance, obesity, and dyslipidemia, thus increased the susceptibility to metabolic syndrome of adult mice. Notably, nutritional supplementation with n-3 PUFA in early life could significantly alleviate the glucose metabolism disorders by increasing insulin sensitivity, inhibiting gluconeogenesis and promoting glycogenesis. In addition, administration with n-3 PUFA in early life remarkably reduced serum and hepatic lipid profiles by mediating the expression of genes related to lipogenesis and ß-oxidation of fatty acids. Dietary n-3 PUFA-deficiency in early life increases the susceptibility to metabolic syndrome of adult offspring, and nutritional supplementation with n-3 PUFA enhances the tolerance to a high-fat diet of adult offspring.

Effects of Rhus coriaria L. hydroalcoholic extract on the lipid and antioxidant profile in high fat diet-induced hepatic steatosis in rats.

Oxidative stress is related to increased fat deposition in the liver, known as hepatic steatosis. The present study is an evaluation of the anti-oxidative and antihyperlipidemic effects of the hydroalcoholic extract of Rhus coriaria L. (HARE) in rats on a high-fat diet (HFD). Twenty male Wistar rats were divided into four groups: control, HFD, HFD + HARE 50 mg/kg/day, and HFD + HARE 250 mg/kg/day for 12 weeks. Animals were weighed weekly and treated with the HARE extract for 12 weeks by gavage. Subsequently, the histopathological changes, oxidative markers, and lipid profile were evaluated. Statistical analysis was performed using the one-way analysis of variance (ANOVA) for multiple comparisons. First, the active ingredients of the extract were determined by HPLC. Then, the levels in the serum lipid profile (TG, cholesterol, HDL, and LDL) in rats fed with the HFD + HARE were analyzed where a significant reduction was observed. The HFD proved to increase the activity of the liver enzymes, the serum lipid levels, and the malondialdehyde (MDA) level. The ferric-reducing antioxidant activity power (FRAP), catalase (CAT), and superoxide dismutase (SOD) catalytic activity were reduced in the liver homogenate of HFD rats compared to the controls. Additionally, the aforementioned liver enzymes activities were reduced in response to HARE. Evaluation of oxidative stress determined a reduction in the MDA level while a raised FRAP was confirmed. In accordance with the present results, histopathological observations have also demonstrated that HARE ameliorated grade-1 hepatic steatosis induced by HFD. Taken together, the findings of this study introduce HARE as a future potential therapeutic agent in treating hepatic steatosis and reducing oxidative damages of an HFD in the liver.

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.

Sasa quelpaertensis Leaf Extract Ameliorates Dyslipidemia, Insulin Resistance, and Hepatic Lipid Accumulation in High-Fructose-Diet-Fed Rats.

BACKGROUND: Increased dietary fructose consumption is closely associated with lipid and glucose metabolic disorders. Sasa quelpaertensis Nakai possesses various health-promoting properties, but there has been no research on its protective effect against fructose-induced metabolic dysfunction. In this study, we investigated the effects of S. quelpaertensis leaf extract (SQE) on metabolic dysfunction in high-fructose-diet-fed rats. METHODS: Animals were fed a 46% carbohydrate diet, a 60% high-fructose diet, or a 60% high-fructose diet with SQE (500 mg/kg of body weight (BW)/day) in drinking water for 16 weeks. Serum biochemical parameters were measured and the effects of SQE on hepatic histology, protein expression, and transcriptome profiles were investigated. RESULTS: SQE improved dyslipidemia and insulin resistance induced in high-fructose-diet-fed rats. SQE ameliorated the lipid accumulation and inflammatory response in liver tissues by modulating the expressions of key proteins related to lipid metabolism and antioxidant response. SQE significantly enriched the genes related to the metabolic pathway, namely, the tumor necrosis factor (TNF) signaling pathway and the PI3K-Akt signaling pathway. CONCLUSIONS: SQE could effectively prevent dyslipidemia, insulin resistance, and hepatic lipid accumulation by regulation of metabolism-related gene expressions, suggesting its role as a functional ingredient to prevent lifestyle-related metabolic disorders.