High-refined Carbohydrate Diet Research Articles

Eosinophils protect from metabolic alterations triggered by obesity.

Eosinophils are generally related to helminth infections or allergies. Their association with metabolic alterations and adipose tissue (AT) remodeling has been demonstrated mainly in animal models of obesity. However, their physiological role in driving metabolic features has not yet been well described. Herein, we aimed to evaluate the participation of eosinophils in metabolic and adipose tissue homeostasis in mice and humans, focusing on a translational perspective. Male BALB/c wild-type (WT) mice and GATA-1 knockout (Δdb/GATA-1-/-) mice were followed until 16-week-age in a regular diet or were fed with a high-refined-carbohydrate (HC) diet or high-fat (HF) diet for eight weeks. In subjects with obesity, clinical parameters and omental AT gene expression were evaluated. Eosinophils lack in mice fed a regular diet induced insulin resistance and increased adiposity. Their adipose tissue showed augmented cytokine levels, which could be attributed to increased leukocytes in the tissue, such as neutrophils and pro-inflammatory macrophages. Bone marrow transplant from WT mice to Δdb/GATA-1-/- mice showed some improvement in glucose metabolism with lower adipose tissue mass accretion. Upon an unhealthy diet challenge, Δdb/GATA-1-/- mice fed HC diet showed a mild degree of adiposity and glucose metabolic dysfunction severe in those mice fed HF diet. The expression of eosinophil markers in omental AT from humans with severe obesity was positively correlated to eosinophil cytokines and insulin sensitivity surrogate markers and negatively correlated to systemic insulin, HOMA-IR, and android fat mass. Eosinophils seem to have a physiological role by controlling systemic and adipose tissue metabolic homeostasis by modulating glucose metabolism, inflammation, and visceral fat expansion, even in lean mice. Indeed, eosinophils also seem to modulate glucose homeostasis in human obesity.

Acute exercise modulates the inflammatory response in adipose tissue in both lean and obese mice

ObjectivesAcute physical exercise acts as a metabolic stressor, promoting activation of the immune system, and this response could be relevant in the adipose tissue remodeling process. In addition, some cytokines have important functions in lipolysis. Because chronic exercise improves obesity-related metabolic and inflammatory dysfunction, herein we investigated the effect of acute exercise on the inflammatory responses in the adipose tissues of lean and obese mice. MethodsLean mice were fed a standard chow diet, whereas obese mice were fed a high-refined carbohydrate diet for 8 wk. Both groups were subjected to 60 min of moderate-intensity exercise. ResultsIn the epididymal adipose tissue of lean mice, exercise enhanced interleukin (IL)-6 and tumor necrosis factor-α levels, which correlated positively with increased serum free fatty acid concentrations. In vivo confocal imaging of epididymal adipose tissue vessels revealed higher recruitment of neutrophils after exercise. Also, the number of leukocytes expressing CD11b+F480– was elevated 6 h after exercise. Similarly, the chemokine (C-X-C motif) ligand 1 level increased at 6 h and remained high until 24 h after exercise. Myeloperoxidase activity was increased at 6, 12, and 24 h after exercise. Surprisingly, however, no changes were observed in epididymal adipose tissue from obese mice, considering proinflammatory cytokines (IL-6 and tumor necrosis factor-α). On the other hand, IL-13, IL-4, and IL-10 levels were higher in obese mice after exercise. ConclusionsThese data suggest that acute exercise promotes an inflammatory response in the adipose tissue of lean mice that is observed as part of its role in adipose tissue remodeling. In contrast, acute exercise promotes an antiinflammatory response in adipose tissue from obese mice, likely as an important tool for restoring homeostasis.

Subacute high-refined carbohydrate diet leads to abnormal reproductive control of the hypothalamic-pituitary axis in female rats

We previously reported that female rats placed on a diet containing refined carbohydrates (HCD) resulted in obesity and reproductive abnormalities, such as high serum LH concentration and abnormal ovarian function. However, the impacts at the hypothalamic-pituitary (HP) function, specifically regarding pathways linked to reproductive axis modulation are unknown. In this study, we assessed whether subacute feeding with HCD results in abnormal reproductive control in the HP axis. Female rats were fed with HCD for 15 days and reproductive HP axis morphophysiology was assessed. HCD reduced hypothalamic mRNA expression (Kiss1, Lepr, and Amhr2) and increased pituitary LHβ+ cells. These changes likely contribute to the increase in serum LH concentration observed in HCD. Blunted estrogen negative feedback was observed in HCD, with increased kisspeptin protein expression in the arcuate nucleus of the hypothalamus (ARH), lower LHβ+ cells and LH concentration in ovariectomized (OVX)+HCD rats. Thus, these data suggest that HCD feeding led to female abnormal reproductive control of HP axis.

Effect of high-refined carbohydrate diet on intestinal integrity

ObjectivesOne of the leading causes of obesity is the consumption of excess nutrients. Obesity is characterized by adipose tissue expansion, chronic low-grade inflammation, and metabolic alterations. Although consumption of a high-fat diet has been demonstrated to be a diet-induced obesity model associated with gut disorders, the same effect is not well explored in a mild-obesity model induced by high-refined carbohydrate (HC) diet intake. The intestinal tract barrier comprises mucus, epithelial cells, tight junctions, immune cells, and gut microbiota. This system is susceptible to dysfunction by excess dietary components that could increase intestinal permeability and bacterial translocation. The aim of this study was to evaluate whether an HC diet and the alterations resulting from its intake are linked to small intestine changes. MethodsMale BALB/c mice were fed a chow or an HC diet for 8 wk. ResultsAlthough differences in body weight gain were not observed between the groups, mice fed the HC diet showed increased adiposity associated with metabolic alterations. The interferon-γ expression and myeloperoxidase levels were increased in the small intestine in mice fed an HC diet. However, the intestinal villi length, the expression of tight junctions (zonula occludens-1 and claudin-4) and tumor necrosis factor-α cytokine, and the percentage of intraepithelial lymphocytes did not differ in the jejunum or ileum between the groups. We did not observe differences in intestinal permeability and bacterial translocation. ConclusionMetabolic alterations caused by consumption of an HC diet lead to a mild obesity state that does not necessarily involve significant changes in intestinal integrity.

Cardiac disturbances and changes in tissue cytokine levels in mice fed with a high-refined carbohydrate diet

AimsThe consumption of highly refined carbohydrates increases systemic inflammatory markers, but its potential to exert direct myocardial inflammation is uncertain. Herein, we addressed the impact of a high-refined carbohydrate (HC) diet on mice heart and local inflammation over time. Main methodsBALB/c mice were fed with a standard chow (control) or an isocaloric HC diet for 2, 4, or 8 weeks (HC groups), in which the morphometry of heart sections and contractile analyses by invasive catheterization and Langendorff-perfused hearts were assessed. Cytokines levels by ELISA, matrix metalloproteinase (MMP) activity by zymography, in situ reactive oxygen species (ROS) staining and lipid peroxidation-induced TBARS levels, were also determined. Key findingsHC diet fed mice displayed left ventricular hypertrophy and interstitial fibrosis in all times analyzed, which was confirmed by echocardiographic analyses of 8HC group. Impaired contractility indices of HC groups were observed by left ventricular catheterization, whereas ex vivo and in vitro indices of contraction under isoprenaline-stimulation were higher in HC-fed mice compared with controls. Peak levels of TNF-α, TGF-β, ROS, TBARS, and MMP-2 occur independently of HC diet time. However, a long-lasting local reduction of the anti-inflammatory cytokine IL-10 was found, which was linearly correlated to the decline of systolic function in vivo. SignificanceAltogether, the results indicate that short-term consumption of HC diet negatively impacts the balance of anti-inflammatory defenses and proinflammatory/profibrotic mediators in the heart, which can contribute to HC diet-induced morphofunctional cardiac alterations.

High-refined carbohydrate diet alters different metabolic functions in female rats

A diet containing refined carbohydrate (HCD) caused obesity and white adipose tissue (WAT) abnormalities, but it is unclear if HCD is linked with other metabolic dysfunctions in female models. Thus, we assessed whether HCD results in WAT, pancreas, liver, skeletal muscle (SM) and thyroid (TH) abnormalities in female rats. Female rats were fed with HCD for 15 days and metabolic morphophysiology, inflammation, oxidative stress (OS), and fibrosis markers were assessed. HCD rats presented large adipocytes, hyperleptinemia, and WAT OS. HCD caused irregular glucose metabolism, low insulin levels, and large pancreatic isle. Granulomas, reduced glycogen, and OS were observed in HCD livers. HCD caused hypertrophy and increased in glycogen in SM. HCD caused irregular TH morphophysiology, reduced colloid area and high T3 levels. In all selected tissues, inflammation and fibrosis were observed in HCD rats. Collectively, these data suggest that the HCD impairs metabolic function linked with irregularities in WAT, pancreas, liver, SM and TH in female rats.

Cannabidiol ameliorates the anxiogenic and compulsive-like behaviors induced by chronic consumption of a high-carbohydrate diet in male mice.

The excessive consumption of ultra-processed foods and the development of obesity has been associated with several comorbidities, including psychiatric disorders. Excess fat tissue promotes a low-intensity inflammatory state, mainly in the white tissue, which is essential in developing metabolic alterations and influences brain homeostasis. In this scenario, Cannabidiol (CBD), a compound from Cannabis sativa, has presented anxiolytic and anti-inflammatory effects in murine models. This study verified whether CBD treatment would ameliorate the compulsive-like and anxiety-like behaviors observed after mice's chronic consumption of a high-refined carbohydrate (HC) diet. BALB/c male mice received a control or HC diet for 12 weeks followed by vehicle and CBD (30mg/Kg, i.p.) administration, and their behavior was evaluated in the Marble Burying test (MB) and Novel Suppressing Feeding test (NSF). The sub-chronic, but not acute, treatment with CBD attenuated the compulsive-like and anxiogenic-like behavior induced by the HC diet. Our data reinforced the harmful effects of the HC diet's chronic consumption on compulsive and anxious behaviors and the potential of CBD as a drug treatment for psychiatric disorders associated with obesity.

Beta-Cryptoxanthin Supplementation Protects Against Liver Cancer Progression and Correlates With Altered Targeted and Untargeted Metabolomic Profiles in Mice

ObjectivesNonalcoholic fatty liver disease (NAFLD)-associated hepatocellular carcinoma (HCC) is expected to increase globally in the upcoming years. Diets high in refined carbohydrates and added sugars (HRCD) have been linked to NAFLD progression. Previous studies have demonstrated that retinoids possess anti-tumorigenic properties, yet less is known about whether upstream provitamin A carotenoids exhibit similar characteristics. We recently demonstrated that dietary beta-cryptoxanthin (BCX), a provitamin A carotenoid, decreased NAFLD severity and HCC progression in diethylnitrosamine (DEN)-initiated, high refined carbohydrate diet (HRCD)-fed mice. In this study, we evaluated the effects of dietary BCX supplementation on modulating plasma biomarkers, hepatic vitamin A status, and plasma metabolomic profiles in our DEN-initiated, HRCD-promoted model of HCC. MethodsMale, six-week-old C57BL/6J mice were injected with DEN (25 mg/kg BW) and a fed a HRCD (66.5% carbs including sucrose) with or without BCX supplementation (10 mg/kg diet) for 24 weeks. Using plasma samples, we performed metabolomics using our UHPLC-QTOF-MS platform, a targeted Biocrates MxP Quant 500 kit, and a complimentary untargeted analysis of phospholipids from the METLIN database to identify metabolites which correlate with primary outcomes. Hepatic vitamin A levels were determined via HPLC. ResultsCompared to HRCD-fed, DEN-injected mice, mice fed BCX displayed significantly lower tumor burden and steatosis, higher hepatic vitamin A status, and lower plasma levels of alanine transaminase (ALT) and lactate dehydrogenase (LDH). Moderate negative correlations were also identified amongst hepatic vitamin A levels and primary outcomes, such as HCC tumor number, steatosis score, and relevant biomarkers. Our metabolomics data showed significant modulations in metabolites with BCX treatment from phosphatidylcholine, sphingomyelin, ceramide, bile acid, and other phospholipid classes. ConclusionsBCX supplementation significantly reduced HCC severity, increased hepatic vitamin A status, reduced plasma levels of ALT and LDH, and altered several lipid-related classes of metabolites, thus supporting a chemopreventive potential for BCX against HRCD-promoted HCC development. Funding SourcesUSDA/ARS and NIFA/AFRI.

Ablation of Carotenoid Cleavage Enzymes BCO1 & BCO2 Alters Gut Microbial and Plasma Metabolomic Profiles in High Refined Carbohydrate Diet-Fed Mice

Objectivesβ-Carotene-15,15′-oxygenase (BCO1) and β-carotene-9′,10′-oxygenase (BCO2) cleave carotenoids to form vitamin A or apo-carotenoid species. Beyond these roles, BCO1 and BCO2 have been implicated in modulating lipid, cholesterol, and oxidative stress-related processes, yet less is known about their combined influence on shaping gut microbial and plasma metabolic profiles. Current intake of refined carbohydrates and added sugars exceeds the recommendations within the Dietary Guidelines for Americans, which may contribute to the development of nonalcoholic fatty liver disease (NAFLD). In the present study, we aimed to uncover whether mice with systemic ablation of BCO1-/-/BCO2-/- (DKO) display distinctive phenotypes in response to a high refined carbohydrate diet (HRCD) model of NAFLD. MethodsMale, six-week-old C57BL/6J wild type mice (WT) and DKO mice were fed a chow diet or a HRCD (66.5% carbs including sucrose) for 24 weeks. We used fecal and plasma samples to respectively perform 16S rDNA sequencing, and both targeted and untargeted metabolomics using our UHPLC-QTOF-MS platform, a targeted Biocrates MxP Quant 500 kit, and a complimentary untargeted analysis of phospholipids from the METLIN database. Data were analyzed using QIIME2-DEseq2, MetaboAnalyst 5.0, MassHunter Qualitative Analysis, and MicrobiomeAnalyst. ResultsHRCD-fed WT and DKO mice developed similar levels of hepatic steatosis although DKO mice had significantly higher hepatic levels of malondialdehyde (MDA). Interestingly, in both chow-fed and HRCD-fed DKO mice, plasma adiponectin and hepatic bile acids were significantly lower compared to respective WT groups. Our metabolomics data revealed that DKO mice displayed significant alterations in ceramide, cholesterol ester, triglyceride, and phospholipid classes under both chow and HRCD conditions. Additionally, when compared to HRCD-fed WT mice, HRCD-fed DKO mice displayed significantly reduced alpha diversity and possessed significant compositional differences based on Bray Curtis dissimilarity measures. ConclusionsBCO1/BCO2 DKO mice display altered metabolomic and gut microbial profiles. Carotenoid cleavage enzymes affect diverse physiological processes, which involve lipid metabolism and the gut microbiome. Funding SourcesUSDA/ARS and NIFA/AFRI.

Sexually Dimorphic Responses to a High-Refined Carbohydrate Diet in a Nonalcoholic Fatty Liver Disease Mouse Model

Abstract Objectives Nonalcoholic fatty liver disease (NAFLD) incidence and prevalence have been reported to be higher in men than women, however, the effects of sexual dimorphism on NAFLD risk and progression have not been adequately examined. Our lab has previously shown that a liquid high-refined carbohydrate diet (HRCD) induced more severe hepatic steatosis compared to an isocaloric high fat diet in male mice. Also, HRCD-induced reduction in sirtuin 1 (SIRT1), an NAD-dependent deacetylase protein, has previously been implicated in NAFLD pathogenesis. Therefore, we investigated whether there were sexually dimorphic responses to a liquid high-refined carbohydrate diet (HRCD) in male and female, wildtype and SIRT1-deficient mice. Methods Male and female 10–12-week-old wildtype (SIRT1 +/+: n = 12; M = 6, F = 6) and mice carrying a heterozygous H355Y SIRT1 point mutation (SIRT1 +/y: n = 14; M = 7, F = 7) were both fed a HRCD (Lieber-DeCarli liquid diet supplemented with maltose dextrin; 47% energy from refined carbohydrate, Dyets, #710,260) for 5 weeks and 9 weeks. Hepatic gene expression was examined using qRT-PCR. Plasma ALT (alanine transaminase) and hepatic MDA (malondialdehyde) levels were determined using colorimetric assay kits. Hepatic steatosis scoring was conducted by analyzing Hematoxylin and Eosin (H&E) stains. Results 9 weeks of HRCD induced significantly less hepatic steatosis in female mice irrespective of genotype compared to male mice as determined by grading of H&E stains (P < 0.05). Furthermore, liver expression of several fatty acid oxidation genes (CPT1, ACOX1) was significantly higher in females (P < 0.05), which potentially suggests increased fatty acid oxidation. Additionally, female mice had significantly increased antioxidant gene expression (GPX4, SOD1, SOD2, Catalase) and significantly lower hepatic MDA (P < 0.05), which indicate an increased capacity to mitigate oxidative stress. Lastly, plasma ALT levels were significantly lower in females compared to males after 9 weeks of HRCD (P < 0.05). Conclusions Collectively, these data indicate that female mice are moderately protected against HRCD-induced NAFLD compared to male mice, potentially through increased hepatic fatty acid oxidation and superior mitigation of oxidative stress due to increased antioxidant system gene expression in the liver. Funding Sources HNRCA, USDA/ARS Grants.

High-refined carbohydrate diet consumption induces neuroinflammation and anxiety-like behavior in mice

Consumption of poor nutrients diets is associated with fat tissue expansion and with a central and peripheral low-grade inflammation. In this sense, the microglial cells in the central nervous system are activated and release pro-inflammatory cytokines that up-regulate the inducible nitric oxide synthase (iNOS), promoting Nitric Oxide (NO) production. The excess of NO has been proposed to facilitate anxious states in humans and rodents. We evaluated whether consumption of a high-refined carbohydrate-containing diet (HC) in mice induced anxiety-like behavior in the Novelty Suppressed Feeding Test (NFST) trough facilitation of NO, in the prefrontal cortex (PFC) and hippocampus (HIP). We also verified if HC diet induces activation of microglial cells, alterations in cytokine and leptin levels in such regions. Male BALB/c mice received a standard diet or a HC diet for 3 days or 12 weeks. The chronic consumption of HC diet, but not acute, induced an anxiogenic-like effect in the NSF test and an increase in the nitrite levels in the PFC and HIP. The preferential iNOS inhibitor, aminoguanidine (50 mg/kg, i.p.), attenuated such effects. Moreover, microglial cells in the HIP and PFC were activated after chronic consumption of HC diet. Finally, the expression of iNOS in the PFC and TNF, IL6 and leptin levels in HIP were higher in chronically HC fed mice. Taken together, our data reinforce the notion that diets containing high-refined carbohydrate facilitate anxiety-like behavior, mainly after a long period of consumption. The mechanisms involve, at least in part, the augmentation of neuroinflammatory processes in brain areas responsible for anxiety control.

Dietary β-Cryptoxanthin Inhibits High-Refined Carbohydrate Diet–Induced Fatty Liver via Differential Protective Mechanisms Depending on Carotenoid Cleavage Enzymes in Male Mice

β-Cryptoxanthin (BCX), a provitamin A carotenoid shown to protect against nonalcoholic fatty liver disease (NAFLD), can be cleaved by β-carotene-15,15'-oxygenase (BCO1) to generate vitamin A, and by β-carotene-9',10'-oxygenase (BCO2) to produce bioactive apo-carotenoids. BCO1/BCO2 polymorphisms have been associated with variations in plasma carotenoid amounts in both humans and animals. We investigated whether BCX feeding inhibits high refined-carbohydrate diet (HRCD)-induced NAFLD, dependent or independent of BCO1/BCO2. Six-week-old male wild-type (WT) and BCO1-/-/BCO2-/- double knockout (DKO) mice were randomly fed HRCD (66.5% of energy from carbohydrate) with or without BCX (10 mg/kg diet) for 24 wk. Pathological and biochemical variables were analyzed in the liver and mesenteric adipose tissues (MATs). Data were analyzed by 2-factor ANOVA. Compared to their respective HRCD controls, BCX reduced hepatic steatosis severity by 33‒43% and hepatic total cholesterol by 43‒70% in both WT and DKO mice (P<0.01). Hepatic concentrations of BCX, but not retinol and retinyl palmitate, were 33-fold higher in DKO mice than in WT mice (P<0.001). BCX feeding increased the hepatic fatty acid oxidation protein peroxisome proliferator-activated receptor-α, and the cholesterol efflux gene ATP-binding cassette transporter5, and suppressed the lipogenesis gene acetyl-CoA carboxylase 1 (Acc1) in the MAT of WT mice but not DKO mice (P<0.05). BCX feeding decreased the hepatic lipogenesis proteins ACC and stearoyl-CoA desaturase-1 (3-fold and 5-fold) and the cholesterol synthesis genes 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase and HMG-CoA synthase 1 (2.7-fold and 1.8-fold) and increased the cholesterol catabolism gene cholesterol 7α-hydroxylase (1.9-fold) in the DKO but not WT mice (P<0.05). BCX feeding increased hepatic protein sirtuin1 (2.5-fold) and AMP-activated protein kinase (9-fold) and decreased hepatic farnesoid X receptor protein (80%) and the inflammatory cytokine gene Il6 (6-fold) in the MAT of DKO mice but not WT mice (P<0.05). BCX feeding mitigates HRCD-induced NAFLD in both WT and DKO mice through different mechanisms in the liver-MAT axis, depending on the presence or absence of BCO1/BCO2.

The High Refined Carbohydrate Diet Promotes Renal Injury in Mice Exposed to Cigarette Smoke

The High Refined Carbohydrate Diet Promotes Renal Injury in Mice Exposed to Cigarette Smoke

β-Cryptoxanthin Prevents Non-alcoholic Fatty Liver Disease Through Different Mechanisms Depending on the Presence or Absence of Carotenoid Cleavage Enzymes (FS06-03-192)

Objectivesβ-Cryptoxanthin (BCX), a provitamin A carotenoid, is cleaved by carotenoid cleavage enzymes including β-carotene-15, 15′-oxygenase (BCO1) to generate vitamin A, and β-carotene-9′, 10′-oxygenase (BCO2) which yields bioactive apo-carotenoids. Dietary supplementation of BCX can prevent non-alcoholic fatty liver disease (NAFLD), which is the most common chronic liver disease worldwide. This study aimed to investigate whether BCX-mediated protection against NAFLD proceeds through the liver-mesenteric adipose tissue axis depending on the presence or absence of BCO1/BCO2. MethodsSix-week-old male wild type (WT) mice (n = 30) and congenic BCO1–/–/BCO2–/– double KO (DKO) mice (n = 30) were randomly fed either a high-refined carbohydrate diet (HRCD, 66.5% CHO) or HRCD with BCX (10 mg/kg diet) for 24 weeks. ResultsHepatic levels of BCX, but not retinol and retinyl palmitate, were significantly (P < 0.001) higher (33-fold) in the DKO mice than in the WT mice. BCX significantly reduced hepatic steatosis and total cholesterol levels in both WT and DKO mice in comparison with their HRCD counterparts (P < 0.01 and P < 0.001, respectively), albeit through different mechanisms. In the liver, BCX significantly (P < 0.05) down-regulated mRNA for cholesterol synthesis genes Hmgcr and Hmgs1 and nuclear bile acid receptor Fxr, and up-regulated cholesterol catabolism gene Cyp7a1 in DKO mice in comparison with their HRCD counterparts. Furthermore, BCX significantly (P < 0.05) up-regulated antioxidant enzymes Sod1 and Cat in DKO mice in comparison with HRCD littermates. In WT mice, BCX significantly (P < 0.05) up-regulated hepatic mRNA for cholesterol efflux gene Abcg5 and nuclear receptor Shp in comparison with their HRCD counterparts. In mesenteric adipose tissue, BCX significantly down-regulated (P < 0.05) the inflammatory cytokine Il6 and up-regulated fatty acid β-oxidation marker Acox1 and Sirt1 in DKO mice but significantly (P < 0.05) suppressed lipogenesis marker Acc1 in WT mice. ConclusionsThe protective effects of dietary BCX against HRCD-induced NAFLD are achieved through different molecular mechanisms in the liver-mesenteric adipose tissue axis and depend on the carotenoid cleavage enzymes. Funding SourcesNIFA/AFRI (2017-67017-26363) and USDA/ARS (58-1950-0074).

Chemical characterization, antihyperlipidaemic and antihyperglycemic effects of Brazilian bitter quina species in mice consuming a high-refined carbohydrate diet

Abstract Quina is the popular name for species of Cinchona, native to Peru and whose barks produce quinine. Currently, quinine is also used as a bitter additive in tonic water and drinks. Cinchona species do not occur in Brazil, but other species are known as quina, due their bitter taste and use as digestive tonics. In this study, six species of Brazilian quina were chemically characterized and three of them evaluated as antihyperlipidaemic and antihyperglycemic agents. The chemical composition was determined by spectroscopy, HPLC-DAD and LC-MS. Plasma concentrations of glucose and cholesterol were strongly reduced in animals receiving extracts from Baccharis trimera and Strychnos pseudoquina. These effects were attributed to the presence of higher concentrations of flavonoids and organic acids. S. pseudoquina also promoted a significant reduction of triglyceride, as well as a better fat distribution. The cytotoxicity assay the R. ferruginea and S. pseudoqina species in LD50 are greater than 1000 μg/mL and a percent viability during the 100% assay. B. trimera has already been applied to DL50 with a very high dose of 4.92 μg/mL, presenting a low viability during the analysis and cytotoxic assimilation. The results of this study confirm the role of bitter quina in digestive metabolic disorders.

Ginger (Zingiber officinale Rosc.) Ameliorated Metabolic and Inflammatory Dysfunction Induced by High-Refined Carbohydrate-Containing Diet in Mice.

This study aimed to evaluate the effects and the mechanisms of ginger extract intake in the adiposity gain, metabolic and inflammatory disturbances induced by a high-refined carbohydrate (HC) diet in mice. Ginger extract at doses of 200, 600, and 1800 mg/kg was supplemented in the daily food of obese Balb/c mice during an 8-week experiment. Our findings indicate that consumption of high doses of ginger extracts prevents the increase of adiposity induced by HC diet, improves lipid profile, and promotes decrease of inflammatory markers in mice. We showed that ginger addition to HC diet leads to decrease in the recruitment of cells visualized in vivo in the microvasculature of adipose tissue, decrease of inflammatory cytokines, and increase of adiponectin serum levels. These results indicate that the consumption of ginger decreases the negative metabolic consequences induced by HC diet.

Aerobic training reduces immune cell recruitment and cytokine levels in adipose tissue in obese mice

Obesity is associated with an energy imbalance that results from excessive energy intake, low diet quality, and a sedentary lifestyle. The increased consumption of a high-refined carbohydrate (HC) diet is strongly related to higher adiposity and low-grade inflammation. Aerobic training is a well-known nonpharmacological intervention to treat obesity and metabolic disturbances. However, the mechanisms through which aerobic training ameliorates the low-grade inflammation induced by an HC diet should be further investigated. Our hypothesis herein was that aerobic training would decrease the recruitment of leukocytes in adipose tissue, thereby reducing the levels of cytokines and improving metabolism in mice fed an HC diet. Male Balb/c mice were assigned to the following groups: control diet/nontrained (C-NT), control diet/trained (C-T), high-refined carbohydrate diet/nontrained (HC-NT), and high-refined carbohydrate diet/trained (HC-T). Mice were submitted to moderate-intensity training sessions that consisted of running 60 min per day for 8 weeks. An intravital microscopy technique was performed in vivo in anesthetized mice to visualize the microvasculature of the adipose tissue. The HC diet induced obesity and increased the influx of immune cells into the adipose tissue. In contrast, HC-T mice presented a lower adiposity and adipocyte area. Furthermore, relative to HC-NT mice, HC-T mice showed increased resting energy expenditure, decreased recruitment of immune cells in the adipose tissue, reduced cytokine levels, and ameliorated hyperglycemia and fatty liver deposition. Collectively, our data enhance understanding about the anti-inflammatory effect of aerobic training and shed light on the adipose tissue-mediated mechanisms by which training promotes a healthier metabolic profile.

Effects of Rudgea viburnoides (Cham.) Benth. (Rubiaceae) Leaves on Metabolic and Inflammatory Dysfunction Induced by High Refined Carbohydrate-Containing Diet in Mice.

Obesity is characterized by a chronic low-grade inflammation, which has been shown to be involved in the development of comorbidities such as insulin resistance, glucose intolerance, and liver damage. Phytochemicals found in plants may modulate inflammation and improve health problems associated with the excess of adiposity. Teas prepared with many plants are used in Brazil for losing weight. In this study, we evaluated the potential of Rudgea viburnoides (Cham.) Benth. on metabolic and inflammatory disarrangement induced by high refined carbohydrate (HC)-containing diet in mice. BALB/c mice were fed with chow or HC diet for 8 weeks. After this period, the HC diet was supplemented for 4 weeks with three different doses, 40, 80, and 160 mg/kg, of crude extract of R. viburnoides. Ethanol extract at the lowest dose (40 mg/kg) reduced adipocyte size, and improved glucose tolerance and insulin sensitivity. A lower concentration of proinflammatory mediators such as tumor necrosis factor-α, interleukin-6, and CCL2 in the liver and adipose tissue, and reduced levels of cholesterol and resistin in the serum were also observed. High concentrations of chlorogenic and caffeic acids, and the flavonoids, rutin and quercetin, were confirmed by high-performance liquid chromatography/diode array detector. Therefore, these data confirm the potential of R. viburnoides leaves as nutraceutical agents for the treatment of metabolic and inflammatory changes associated with obesity.

A high-refined carbohydrate diet facilitates compulsive-like behavior in mice through the nitric oxide pathway

Obesity is characterized by abnormal adipose tissue expansion and is associated with chronic inflammation. Obesity itself may induce several comorbidities, including psychiatric disorders. It has been previously demonstrated that proinflammatory cytokines are able to up-regulate inducible nitric oxide synthase (iNOS) and nitric oxide (NO) release, which both have a role in compulsive related behaviors. ObjectiveTo evaluate whether acute or chronic consumption of a high-refined carbohydrate-containing (HC) diet will modify burying-behavior in the Marble Burying Test (MBT) through augmentation of NO signaling in the striatum, a brain region related to the reward system. Further, we also verified the effects of chronic consumption of a HC diet on the reinforcing effects induced by cocaine in the Conditioned Place Preference (CPP) test. MethodsMale BALB/c mice received a standard diet (control diet) or a HC diet for 3 days or 12 weeks. ResultsAn increase in burying behavior occurred in the MBT after chronic consumption of a HC diet that was associated with an increase of nitrite levels in the striatum. The pre-treatment with Aminoguanidine (50 mg/kg), a preferential inhibitor of iNOS, prevented such alterations. Additionally, a chronic HC diet also induced a higher expression of iNOS in this region and higher glutamate release from striatal synaptosomes. Neither statistical differences were observed in the expression levels of the neuronal isoform of NOS nor in microglia number and activation. Finally, the reinforcing effects induced by cocaine (15 mg/kg, i.p.) during the expression of the conditioned response in the CPP test were not different between the chronically HC diet fed mice and the control group. However, HC diet-feeding mice presented impairment of cocaine-preference extinction. ConclusionAltogether, our results suggest that the chronic consumption of a HC diet induces compulsive-like behavior through a mechanism possibly associated with NO activation in the striatum.

Evaluation of the effects of extracts of Maytenus imbricata (Celastraceae) on the treatment of inflammatory and metabolic dysfunction induced by high-refined carbohydrate diet.

The Maytenus genus is a member of the Celastraceae family. Numerous medicinal uses were assigned to species of this genus, with the use of roots, bark, and leaves for the treatment of gastric ulcers, as anti-inflammatory, analgesic, antiallergic, antitumor, among others. Several studies have demonstrated that natural products derived from plants have an important role in the prevention and treatment of obesity. Accordingly, we evaluated the effect of Maytenus imbricata extracts in the treatment of obesity induced by diet rich in refined carbohydrate (HC). BALB/c mice were fed chow or HC diet for 8weeks. At the beginning of the 9th week, the HC group was subdivided into three groups: (i) group of animals that continued to consume only HC diet; (ii) the group of animals fed HC diet supplemented with ethyl acetate extract of M. imbricata roots (HC + EAE); (iii) the group of animals fed HC diet supplemented with extract in hexane/ethyl ether (HC + HEE). The period of extracts supplementation was 4weeks. It was observed that EAE and EHE when added to the HC diet modulated the metabolic and inflammatory changes, such as: reduced the adipocytes area, improved glucose intolerance, reduced the levels of triglycerides and resistin in serum, and the number of total leukocytes in blood. In the epididymal adipose tissue, the extracts reduced proinflammatory mediators' concentration. According to the results, it was concluded that the species Maytenus imbricata has the potential to be used for the treatment of obesity.