High Fat Fructose Research Articles

Antioxidative Effects of Black Currant and Cornelian Cherry Juices in Different Tissues of an Experimental Model of Metabolic Syndrome in Rats.

A Western-style diet, rich in fat and simple sugars, is the main risk factor for a significant number of chronic diseases and disorders, as well as for a progression of metabolic syndrome (MetS). One of the key mechanisms involved in MetS development is increased oxidative stress caused by the accumulation of body fat. Some dietary polyphenols have shown a protective role in preventing oxidative-stress-induced damage. We investigated the difference in the oxidative response of plasma, liver, and visceral adipose tissue in rats fed with a high-fat high-fructose (HFF) diet for ten weeks, and the effectiveness of polyphenol-rich juices (black currant (BC) and cornelian cherry (CC)) in HFF-diet-induced oxidative stress prevention. The most prominent impact of the HFF diet on redox parameters was recorded in the liver, whereas adipose tissue showed the most potent protection mechanisms against oxidative stress. Consumption of both juices decreased advanced oxidation protein product (AOPP) level in plasma, increased paraoxonase1 (PON1) activity in the liver, and significantly decreased total oxidative status (TOS) in adipose tissue. BC exerted stronger antioxidative potential than CC and decreased the superoxide anion radical (O2•-) level in the liver. It also reduced TOS, total antioxidative status (TAS), and malondialdehyde (MDA) concentration in adipose tissue. The multiple linear regression analysis has shown that the best predictors of MetS development, estimated through the increase in visceral adiposity, were superoxide dismutase (SOD), AOPP, TOS, and TAS. The consumption of polyphenol-rich juices may provide a convenient approach for the systemic reduction of oxidative stress parameters.

The Effect of Bamboo Tali Leaf Tea on Leptin Levels in Rats Metabolic Syndrome

Metabolic syndrome is a threat to health problems in the world, namely a group of metabolic disorders that occur simultaneously. Obesity is a risk factor for metabolic syndrome. Fat accumulation causes insulin resistance and leptin resistance resulting in weight gain. Tali bamboo leaf tea contains a natural source of antioxidants that can increase insulin sensitivity so that it can reduce leptin levels. This study aims to determine the effect of bamboo1tali leaf tea on leptin levels in rats with metabolic syndrome. This type of research is experimental laboratoric with a Pre-Post Test with a Control Group design. Wistar male white rats, 8 weeks old, and 150 – 250 grams in weight, were fed HFHF (High Fat High Fructose) for 14 days, induced by Nicotinamide and Streptozotocin. Then, the rats were divided into 5 groups, namely negative control, positive control, and 3 treatments of tali bamboo leaf tea (300, 600, and 900 mg/200 g BW) for 28 days. Measurement of leptin levels using the ELISA method.Bamboo leaf tea had a significant effect (p <0.005) on leptin levels in rats with metabolic syndrome. The largest decrease in leptin levels occurred in the TDB3 group which was 82.8% and the lowest decrease in leptin levels occurred in the TDB1 group which was 34.8%. Bamboo leaf tea doses of 300, 600, and 900 mg/200 g BW reduced leptin levels in rats with metabolic syndrome for 28 days.

Histological and immunohistochemical study of the effect of liraglutide in experimental model of non-alcoholic fatty liver disease

ABSTRACT Nonalcoholic fatty liver disease (NAFLD) is known as the accumulation of triglycerides in liver without alcohol consumption. Liraglutide is an analogue of glucagon-like peptide-1 hormone (GLP-1). It is known to decrease blood glucose, body weight and food intake. The present study is designed to study the effect of liraglutide on the experimental model of NAFLD. Thirty-six adult male albino rats were divided into three groups. Group I was the control group. Group II (FLD group) received a high-fat fructose diet for 16 weeks. Group III (FLD + Lira) received high-fat fructose diet daily for 16 weeks and were injected with Liraglutide intraperitoneally at a dose of 0.6 mg/kg/day in the last 4 weeks. Liver sections were prepared for histological, immunohistochemical and Western blot study of alpha smooth muscle actin and beclin 1. Group II showed macrovesicular and microvesicular steatosis, a strong positive immunoreaction of αSMA (alpha smooth muscle actin) and a weak positive immunoreaction of beclin 1. Group III showed a much better histological picture and a moderate positive immunoreaction of αSMA and beclin 1. In conclusion, liraglutide could treat NAFLD by improving hepatic steatosis and fibrosis, regulating lipid profile and liver functions, and enhancing autophagy.

Could vitamin D protect against high fat diet induced damage in the arcuate nucleus in the rat: histological, immunohistochemical and ultrastructural study

ABSTRACT Obesity is a serious health issue. As regard, the central nervous system, obesity induces neuronal damage. Vitamin D has well-known anti-inflammatory and neuroprotective effects. To detect if vitamin D protects against damage in the arcuate nucleus induced by a high fat-high fructose diet. Forty adult rats were used, and four groups were formed. Group I (negative control) kept on a standard chow diet for six weeks, Group II (positive control) received vitamin D orally once every other day for six weeks, Group III (high fat-high fructose treated group) was given high fat-high fructose diets for six weeks and Group IV (high fat-high fructose and vitamin D treated group) were given high fat-high fructose diets concomitantly with vitamin D for six weeks. High fat-high fructose diet markedly caused histological changes in arcuate neurons as nuclei appeared darkly stained and shrunken with condensed chromatin, and the nucleolus became less prominent. The cytoplasm appeared rarefied with loss of most of the organelles. An increase in neuroglial cells was noticed. The synaptic area showed sparse degenerated mitochondria and a disrupted presynaptic membrane. A high-fat diet has a damaging effect on arcuate neurons and vitamin D alleviates these effects.

Three Varieties of Grape Pomace, with Distinctive Extractable:Non-Extractable Polyphenol Ratios, Differentially Reduce Obesity and Its Complications in Rats Fed a High-Fat High-Fructose Diet.

Grape pomace is a commonly discarded by-product characterized by high extractable (EPP) and non-extractable (NEPP) polyphenol contents which exhibits anti-obesogenic effects. However, the relevance of each fraction needs to be elucidated. In this work, we examined the effects of three pomaces with different concentrations of EPPs and NEPPs on metabolic alterations associated with obesity. The NEPP:EPP ratio of the grape pomaces was 1.48 for Malbec, 1.10 for Garnacha, and 5.76 for Syrah grape varieties. Rats fed a high-fat high-fructose diet supplemented with Malbec grape pomace (HFFD + MAL) Syrah grape pomace (HFFD + SYR) or Garnacha grape pomace (HFFD + GAR) showed significantly less weight gain: 20%, 15%, and 12% less, respectively, compared to HFFD controls. The adiposity index was also significantly decreased by 20% in the HFFD + MAL and HFFD + SYR groups, and by 13% in the HFFD + GAR group. Serum triglycerides were significantly decreased by 46% in the HFFD + MAL group and by 31% in the HFFD + GAR group, compared to the HFFD group, but not in the HFFD + SYR group. All pomace supplementations regulated postprandial glucose in an oral glucose tolerance test. Therefore, grape pomaces containing both EPPs and NEPPs exert beneficial effects on body weight and glucose homeostasis, while EPPs seem to control triglyceride levels more effectively.

The Mechanisms of Neochlorogenic Acid (3-Caffeoylquinic Acid) in Improving glucose and Lipid Metabolism in Rats with Insulin Resistance Induced by A High Fat-High Fructose Diet

This study investigated the effects and the mechanism of actions of neochlorogenic acid (3-caffeoylquinic acid; 3-CQA) on glucose and lipid metabolism in rats fed a high fat-high fructose diet (HFFD). Male rats were fed HFFD (40 % lard and 20 % fructose) for 16 weeks. At the 10th week, the HFFD rats were split into 3 groups: HFFD receiving distilled water (HFFD control group), HFFD receiving 3-CQA 50 mg/kg and HFFD receiving metformin 200 mg/kg once daily for a further 6 weeks. At the end of treatment, fasting blood glucose (FBG), oral glucose-tolerance test (OGTT), lipid profile, insulin, leptin, adiponectin, markers of oxidative stress, and hepatic triglyceride content were measured. Liver, adipose tissue, and skeletal muscle were collected for histological, gene and protein examinations. Compared to the HFFD control group, the 3-CQA group exhibited significantly reduced FBG, insulin and leptin levels, and improved OGTT. Serum adiponectin increased and lipid profiles were normalized. Hepatic triglyceride was reduced with a decrease in lipid droplets in liver histological sections. Levels of serum SOD and CAT activity, and MDA were reversed by 3-CQA treatment. Moreover, 3-CQA significantly reduced the expression of adipocyte pro-inflammatory cytokine genes (MCP-1, TNF-α, and IL-6), hepatic lipogenic genes (SREBP1c, FAS, and GPAT), and hepatic gluconeogenic genes (PEPCK and G6Pase). Additionally, 3-CQA increased expression of muscle GLUT4 gene, and of GLUT4 protein with increased p-AKT and p-AMPK in skeletal muscle. In conclusion, 3-CQA improves glucose and lipid metabolism plausibly by decreasing oxidative stress and inflammation-induced insulin resistance, downregulating the expression of lipogenic and gluconeogenic genes, and enhancing insulin signaling in HFFD-induced insulin-resistant rats. HIGHLIGHTS Neochlorogenic acid (3-CQA) improves glucose and lipid metabolism by decreasing insulin resistance Neochlorogenic acid (3-CQA) deceases insulin resistance due to its activities in ameliorating obesity, oxidative stress, and adipose tissue inflammation The beneficial effects of Neochlorogenic acid (3-CQA) to improve glucose and lipid homeostasis may be mediated via suppression of hepatic glucose production and lipogenesis, and activation of muscle glucose uptake and AKT and AMPK pathways GRAPHICAL ABSTRACT

6-gingerol ameliorates weight gain and insulin resistance in metabolic syndrome rats by regulating adipocytokines

Metabolic syndrome (MetS) can lead to increase of insulin resistance (IR) and visceral adipose tissue production of adipocytokines. 6-gingerol is known to have antioxidant and anti-inflammatory activities. Aim of this study is to investigate the effects of 6-gingerol on high-fat high-fructose (HFHF) diet-induced weight gain and IR in rats through modulation of adipocytokines. To induce MetS, male Sprague-Dawley rats were fed with a HFHF diet for 16 weeks and at Week 8, single-dose low-dose streptozotocin (22 mg/kg) were intraperitoneally injected. After 8 weeks of HFHF diet feeding, the rats were treated orally with 6-gingerol (50, 100, and 200 mg/kg/day) once daily for 8 weeks. At the end of the study, all animals were terminated, serum, liver, and visceral adipose tissues were harvested for biochemical analysis including the measurements of total cholesterol, triglycerides, HDL-cholesterol, fasting plasma glucose, insulin, leptin, adiponectin, proinflammatory cytokines (TNF-α and IL-6) and liver and adipose tissue histopathology. Biochemical parameters namely serum total cholesterol (243.7 ± 127.6 vs 72.6 ± 3 mg/dL), triglycerides (469.2 ± 164.9 vs 49.3 ± 6.3 mg/dL), fasting plasma glucose (334 ± 49.5 vs 121 ± 8.5 mg/dL), HOMA-IR (0.70 ± 0.24 vs 0.32 ± 0.06), and leptin (6.19 ± 1.24 vs 3.45 ± 0.33 ng/mL) were significantly enhanced, whereas HDL-cholesterol (26.2 ± 5.2 vs 27.9 ± 1.1 mg/dL) and adiponectin level (14.4 ± 5.5 vs 52.8 ± 10.7 ng/mL) were lowered in MetS vs normal control. Moreover, MetS were marked a significant increase in body weight and proinflammatory cytokines. Treatment with 6-gingerol dose-dependently restored all of those alterations towards normal values as well as the accumulation of lipid in liver and adipose tissues. These findings demonstrate that 6-gingerol, in a dose-dependent mode, showed capability of improving weight gain and IR in MetS rats through modulation of adipocytokines.

Untargeted metabolomics and phenotype data indicate the therapeutic and prophylactic potential of Lysimachia candida Lindl. towards high-fat high-fructose-induced metabolic syndrome in rats.

The present study evaluated the therapeutic potential of the medicinal plant Lysimachia candida Lindl. against metabolic syndrome in male SD rats fed with a high-fat high-fructose (HFHF) diet. Methanolic extract of Lysimachia candida Lindl. (250 mg kg-1 body weight p.o.) was administrated to the HFHF-fed rats daily for 20 weeks. Blood samples were collected, and blood glucose levels and relevant biochemical parameters were analysed and used for the assessment of metabolic disease phenotypes. In this study, Lysimachia candida decreased HFHF diet-induced phenotypes of metabolic syndrome, i.e., obesity, blood glucose level, hepatic triglycerides, free fatty acids, and insulin resistance. Liquid chromatography-mass spectrometry-based metabolomics was done to study the dynamics of metabolic changes in the serum during disease progression in the presence and absence of the treatment. Furthermore, multivariate data analysis approaches have been employed to identify metabolites responsible for disease progression. Lysimachia candida Lindl. plant extract restored the metabolites that are involved in the biosynthesis and degradation of amino acids, fatty acid metabolism and vitamin metabolism. Interestingly, the results depicted that the treatment with the plant extract restored the levels of acetylated amino acids and their derivatives, which are involved in the regulation of beta cell function, glucose homeostasis, insulin secretion, and metabolic syndrome phenotypes. Furthermore, we observed restoration in the levels of indole derivatives and N-acetylgalactosamine with the treatment, which indicates a cross-talk between the gut microbiome and the metabolic syndrome. Therefore, the present study revealed the potential mechanism of Lysimachia candida Lindl. extract to prevent metabolic syndrome in rats.

Use of high-fat high-fructose diet for a model of metabolic syndrome in Wistar rats: challenges remain

Metabolic syndrome (MetS) is a global public health challenge and one of the main risk factors for cardiovascular diseases. Its pandemic prevalence created a demand for developing a relevant model system for deep insight into the molecular basis of MetS. Animal models, especially Wistar rats, are commonly used for that purpose. However, there are no standardized protocols in terms of the diet, strain, or age of rats used for the development of MetS. Studies have mostly used a high-fat high-fructose (HFHF) diet in Wistar rats but have reported inconsistent results; thus the main aim of this study was to examine the effects of the HFHF diet on inducing MetS in Wistar rats. We used two different sub-strains of Wistar rats – Hannover and Kyoto – of two different age groups (8 weeks and 4 months). Animals were placed on a modified diet, standard chow diet enriched with 25% fat and 20% fructose. Following 8 weeks of treatment, all groups were tested for indicators of MetS and the treatment was extended to 16 weeks for groups that developed some of the required parameters. None of the tested groups developed MetS after 16 weeks of HFHF diet, suggesting that the HFHF diet is not sufficient to develop at least three out of five (visceral obesity, high fasting glucose, high triglyceride, low HDL-cholesterol, high blood pressure) needed parameters. Based on our results, the addition of some pharmacological agents (e.g., cholic acid) is necessary for establishing a rat model system of MetS.

ЭФФЕКТЫ ТРАНСКРАНИАЛЬНОЙ ЭЛЕКТРОСТИМУЛЯЦИИ НА СИСТЕМНОЕ ВОСПАЛЕНИЕ ПРИ ВЫСОКОКАЛОРИЙНОЙ ДИЕТЕ, ОБОГАЩЕННОЙ ФРУКТОЗОЙ И ЖИРОМ

The study aims to conduct a transcranial electrical stimulation therapy trial in rats influencing the indicators of systemic inflammation dynamics and the percentage content of visceral adipose tissue in a highfat fructose diet. The study included 180 male outbred rats, which were randomly distributed into three groups: the first group had a standard diet; the second group received the high-fat fructose diet; and the third group received both transcranial electrical stimulation therapy and the high-fat fructose diet. Tumor necrosis factor-α, interleukin-15, and interleukin-19 concentrations were measured in blood serum. The percentage of visceral adipose tissue in relation to body weight was calculated. The percentage content of visceral adipose tissue and serum concentration of tumor necrosis factor-α were lower, and interleukin-19 was higher in rats that received transcranial electrical stimulation with a high-fat fructose diet in comparison to the second group, which did not undergo the stimulation. Interleukin-19 level in the blood serum of rats in the second group grew as the trial progressed, whereas the opposite occurred in the third group. There was an inverse relation between the predictive variables of transcranial electrical stimulation, interleukin-19, and the variable of tumor necrosis factor-α. The data obtained in the experiment may also indicate that interleukin-15 cannot be unequivocally considered as a key factor associated with a decrease in visceral adipose tissue content when introducing a high fructose and animal-based saturated fat diet to rats.

Pluchea indica Leaf Extract Alleviates Dyslipidemia and Hepatic Steatosis by Modifying the Expression of Lipid Metabolism-Related Genes in Rats Fed a High Fat-High Fructose Diet.

This study evaluated the effect of Pluchea indica leaf extract (PIE) on dyslipidemia and lipid accumulation in the liver, emphasizing its molecular mechanisms in regulating lipid metabolism in rats fed a high fat-high fructose diet (HFFD). Male rats were fed HFFD (40% lard and 20% fructose) for ten weeks. They were then divided into four groups receiving distilled water, PIE (100 or 300 mg/kg/d), and pioglitazone (10 mg/kg/d) for a further six weeks, during which the HFFD was continued. After the experiment, fasting blood glucose (FBG), oral glucose tolerance (OGT), serum insulin and leptin levels, lipid profiles, and hepatic triglyceride content were measured. Histological examination and expression levels of lipid metabolism-related genes in the liver were measured. HFFD-fed rats indicated a significantly increased FBG, serum leptin, and homeostasis model assessment of insulin resistance (HOMA-IR) scores with impaired OGT and dyslipidemia compared to rats fed a normal diet. PIE significantly reduced FBG, serum leptin, and HOMA-IR scores and improved OGT. Additionally, PIE significantly improved dyslipidemia and decreased serum-free fatty acids and liver triglyceride content. Hepatic histological examination showed a marked reduction lipid accumulation in relation to HFFD controls. Interestingly, PIE significantly downregulated the expression of lipid synthesis-related genes and upregulated the expression of fatty-acid oxidation-related genes. In conclusion, PIE alleviates dyslipidemia and hepatic steatosis in HFFD rats plausibly by increasing insulin resistance and modifying the gene expression associated with lipid metabolism. PIE may be used as preventive nutrition for dyslipidemia and hepatic steatosis.

Avocado oil alleviates non-alcoholic fatty liver disease by improving mitochondrial function, oxidative stress and inflammation in rats fed a high fat-High fructose diet.

Non-alcoholic fatty liver disease (NAFLD) is characterized by lipid accumulation in hepatocytes, and in advanced stages, by inflammation and fibrosis. Excessive ROS production due to mitochondrial dysfunction contributes to NAFLD development, making the decrease in mitochondrial ROS production an emerging target to alleviate NAFLD. Previously, we have shown that avocado oil, a source of several bioactive compounds with antioxidant effects, decreases oxidative stress by improving the function of the mitochondrial electron transport chain (ETC) and decreasing ROS levels in mitochondria of diabetic and hypertensive rats. Therefore, we tested in this work whether avocado oil alleviates NAFLD by attenuating mitochondrial dysfunction, oxidative stress and inflammation. NAFLD was induced in rats by a high fat-high fructose (HF) diet administered for six (HF6) or twelve (HF12) weeks. Hepatic steatosis, hypertrophy and inflammation were detected in both the HF6 and HF12 groups. Hyperglycemia was observed only in the HF12 group. The HF6 and HF12 groups displayed dyslipidemia, impairments in mitochondrial respiration, complex III activity, and electron transfer in cytochromes in the complex III. This led to an increase in the levels of ROS and lipid peroxidation. The substitution of the HF6 diet by standard chow and avocado oil for 6weeks (HF6+AVO + D), or supplementation of the HF12 diet with avocado oil (HF12 + AVO), ameliorated NAFLD, hyperglycemia, dyslipidemia, and counteracted mitochondrial dysfunctions and oxidative stress. The substitution of the HF6 diet by standard chow without avocado oil did not correct many of these abnormalities, confirming that the removal of the HF diet is not enough to counteract NAFLD and mitochondrial dysfunction. In summary, avocado oil decreases NAFLD by improving mitochondrial function, oxidative stress, and inflammation.

Lactiplantibacillus plantarum DSM20174 Attenuates the Progression of Non-Alcoholic Fatty Liver Disease by Modulating Gut Microbiota, Improving Metabolic Risk Factors, and Attenuating Adipose Inflammation.

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease, reaching epidemic proportions worldwide. Targeting the gut-adipose tissue-liver axis by modulating the gut microbiota can be a promising therapeutic approach in NAFLD. Lactiplantibacillus plantarum, a potent lactic-acid-producing bacterium, has been shown to attenuate NAFLD. However, to our knowledge, the possible effect of the Lactiplantibacillus plantarum strain DSM20174 (L.p. DSM20174) on the gut-adipose tissue axis, diminishing inflammatory mediators as fuel for NAFLD progression, is still unknown. Using a NAFLD mouse model fed a high-fat, high-fructose (HFHF) diet for 10 weeks, we show that L.p DSM20174 supplementation of HFHF mice prevented weight gain, improved glucose and lipid homeostasis, and reduced white adipose inflammation and NAFLD progression. Furthermore, 16S rRNA gene sequencing of the faecal microbiota suggested that treatment of HFHF-fed mice with L.p DSM20174 changed the diversity and altered specific bacterial taxa at the levels of family, genus, and species in the gut microbiota. In conclusion, the beneficial effects of L.p DSM20174 in preventing fatty liver progression may be related to modulations in the composition and potential function of gut microbiota associated with lower metabolic risk factors and a reduced M1-like/M2-like ratio of macrophages and proinflammatory cytokine expression in white adipose tissue and liver.

Cytokine modulation by etanercept ameliorates metabolic syndrome and its related complications induced in rats administered a high-fat high-fructose diet

The aim of the present study was to investigate the effect of etanercept (ETA)—an anti-tumor necrosis factor α (TNF-α) monoclonal antibody—on metabolic disorders such as obesity, hypertension, dyslipidemia, and insulin resistance associated with the metabolic syndrome (MS). MS was induced in rats via high-fat high-fructose (HFHF) administration for 8 weeks. Rats were divided into three groups: negative control, HFHF model, and ETA-treated groups [HFHF + ETA (0.8 mg/kg/twice weekly, subcutaneously) administered in the last 4 weeks]. ETA effectively diminished the prominent features of MS via a significant reduction in the percent body weight gain along with the modulation of adipokine levels, resulting in a significant elevation of serum adiponectin consistent with TNF-α and serum leptin level normalization. Moreover, ETA enhanced dyslipidemia and the elevated blood pressure. ETA managed the prominent features of MS and its associated complications via the downregulation of the hepatic inflammatory pathway that induces nonalcoholic steatohepatitis (NASH)—from the expression of Toll-like receptor 4, nuclear factor kappa B, and TNF-α until that of transforming growth factor—in addition to significant improvements in glucose utilization, insulin sensitivity, and liver function parameter activity and histopathological examination. ETA was effective for the treatment of all prominent features of MS and its associated complications, such as type II diabetes mellitus and NASH.

Germinated Millet (Pennisetum glaucum (L.) R. Br.) Flour Improved the Gut Function and Its Microbiota Composition in Rats Fed with High-Fat High-Fructose Diet.

Germinated millet (Pennisetum glaucum (L.) R. Br.) is a source of phenolic compounds that has potential prebiotic action. This study aims at evaluating the action of germinated pearl millet on gut function and its microbiota composition in Wistar rats fed with a high-fat high-fructose (HFHF) diet. In the first stage, lasting eight weeks, the experiment consisted of two groups: AIN-93M (n = 10) and HFHF group (n = 20). In the second stage, which lasted ten weeks, the animals of the AIN-93M group (n = 10) were kept, while the HFHF group was dismembered into HFHF (HFHF diet, n = 10) and HFHF + millet (HFHF added 28.6% of germinated millet flour, n = 10) groups. After the 18th week, the urine of the animals was collected for the analysis of lactulose and mannitol intestinal permeability by urinary excretion. The histomorphometry was analyzed on the proximal colon and the fecal pH, concentration of short-chain fatty acids (SCFA), and sequencing of microbiota were performed in cecum content. The Mothur v.1.44.3 software was used for data analysis of sequencing. Alpha diversity was estimated by Chao1, Shannon, and Simpson indexes. Beta diversity was assessed by PCoA (Principal Coordinate Analysis). The functional predictive analysis was performed with PICRUSt2 software (version 2.1.2-b). Functional traits attributed to normalized OTU abundance were determined by the Kyoto Encyclopedia of Genes and Genomes (KEGG). In the results, germinated millet flour reduced Oscillibacter genus and Desulfobacterota phylum, while increasing the Eggerthellaceae family. Furthermore, germinated millet flour: increased beta diversity, cecum weight, and cecum/body weight ratio; improved gut histological parameters by increasing the depth and thickness of the crypt and the goblet cell count (p < 0.05); reduced (p < 0.05) the fecal pH and mannitol urinary excretion; increased (p < 0.05) the propionate short-chain fatty acid concentration. Thus, germinated millet has the potential to improve the composition of gut microbiota and the intestinal function of rats fed with an HFHF diet.

In Vivo Evaluation of the Cardiometabolic Potential of Grape Pomace: Effect of Applying Instant Controlled Pressure Drop.

Grape pomace (GP) is a source of polyphenols which may be present as free structures or associated with dietary fiber. Instant controlled pressure drop (DIC) is a technology which can modify the association of polyphenols with food matrixes, but how these modifications affect the health benefits associated with GP remains to be elucidated. In this study, in rats fed a high-fat-fructose diet (HFF), we evaluated the in vivo cardiometabolic effects of the modification of polyphenols in GP caused by DIC at 0.2 MPa for 60 s (DIC1) and 0.4 MPa for 120 s (DIC2). These treatments increased anthocyanin and total flavonoid contents, respectively, while all the supplementations caused significant improvements in insulin resistance and plasma triacylglycerols. Thus, the bioactive compounds present in GP (including a major fraction of non-extractable proanthocyanidins) caused these modifications independently of the specific polyphenol profiles which may have resulted from these DIC treatments. Additionally, only intact GP led to an increase in HDL cholesterol, while only DIC2-treated GP improved hepatic steatosis. In conclusion, GP always improves insulin sensitivity in this animal model of obesity, while the different compositions of GP modified by DIC may be associated with other cardiometabolic parameters.

Dietary Supplementation with D-Ribose-L-Cysteine Prevents Hepatic Stress and Pro-Inflammatory Responses in Male Wistar Rats Fed a High-Fructose High-Fat Diet.

Diets rich in fats and fructose are associated with the pathogenesis of oxidative stress-induced non-alcoholic fatty liver disease. Therefore, we investigated the effect of D-ribose-L-cysteine (DRLC) in high-fructose high-fat (HFHF) diet-fed rats. Twenty rats (n = 5), divided into four groups, were simultaneously exposed to HFHF and/or DRLC (250 mg/kg) orally during the 8 weeks of the study. Results showed that HFHF precipitated pro-inflammation and selective disruption of the oxidative stress markers. There were significant decreases in the level of antioxidants such as superoxide dismutase (SOD), glutathione peroxidase (GPX), total antioxidant capacity (TAC), hepatic SOD and GPX. Significant increases in serum levels of uric acid (UA), tumour necrosis factor-alpha (TNF-α), C-reactive protein (CRP) and hepatic Xanthine oxidase (XO) were observed in the HFHF compared to the control. In the HFHF + DRLC group, oxidative stress was mitigated due to differences in serum levels of SOD, GPX, TAC, TNF-α, liver SOD, and XO relative to control. The administration of DRLC alone caused significant reductions in malondialdehyde, UA and CRP and a significant increase in SOD compared to the control. DRLC prevents hepatic and systemic oxidative stress and pro-inflammatory events in HFHF diet-fed rats.

High Fat-High Fructose Diet Elicits Hypogonadotropism Culminating in Autophagy-Mediated Defective Differentiation of Ovarian Follicles.

Pituitary gonadotropins directly govern ovarian functions, which are in turn regulated by the ovarian steroid hormones. The precise interplay of gonadotropins and steroid hormones is critical for follicle growth and differentiation. Furthermore, autophagy regulates ovarian follicle differentiation. However, how the high-fat-high fructose (HFD-HF) diet regulates gonadotropins and facilitates autophagy-mediated follicular differentiation in the ovary is obscure. We fed prepubertal rats (PND 25) an HFD-HF diet until PND 90. The results showed diminished adenohypophyseal GnRHR, PR, and aromatase expression, whereas AR, ERα, PRLR, and inhibin were augmented, resulting in gonadotropins decline. Interestingly, autophagy biomarkers, Beclin-1, ATG5, ATG12, LC3-II, and LAMP1 were reduced but SQSTM1/p62 was augmented in the ovaries of HFD-HF-fed rats, causing autolysosome to aggregation. The diet altered T, E2, P4, PRL, and their receptors status in the ovary, disturbed estrous cyclicity, and delayed vaginal opening. Ovarian histomorphology exhibited numerous cystic and atretic follicles, along with disturbed follicular maturation and ovulation. Moreover, the reduction of FSHR; steroidogenic proteins; receptor proteins AR, ERβ, PR; and signaling proteins Wnt2 and β-catenin was also noticed in the ovary, whereas PRLR, inhibin, and pGSK3β were augmented. In conclusion, exposure to a prepubertal HFD-HF diet leads to hypogonadotropism and the autophagy-mediated defective differentiation of ovarian follicles, abating fertility in adult rats.

Wholegrain fermentation affects gut microbiota composition, phenolic acid metabolism and pancreatic beta cell function in a rodent model of type 2 diabetes.

The intestinal microbiota plays an important role in host metabolism via production of dietary metabolites. Microbiota imbalances are linked to type 2 diabetes (T2D), but dietary modification of the microbiota may promote glycemic control. Using a rodent model of T2D and an in vitro gut model system, this study investigated whether differences in gut microbiota between control mice and mice fed a high-fat, high-fructose (HFHFr) diet influenced the production of phenolic acid metabolites following fermentation of wholegrain (WW) and control wheat (CW). In addition, the study assessed whether changes in metabolite profiles affected pancreatic beta cell function. Fecal samples from control or HFHFr-fed mice were fermented in vitro with 0.1% (w/v) WW or CW for 0, 6, and 24 h. Microbiota composition was determined by bacterial 16S rRNA sequencing and phenolic acid (PA) profiles by UPLC-MS/MS. Cell viability, apoptosis and insulin release from pancreatic MIN6 beta cells and primary mouse islets were assessed in response to fermentation supernatants and selected PAs. HFHFr mice exhibited an overall dysbiotic microbiota with an increase in abundance of proteobacterial taxa (particularly Oxalobacteraceae) and Lachnospiraceae, and a decrease in Lactobacillus. A trend toward restoration of diversity and compositional reorganization was observed following WW fermentation at 6 h, although after 24 h, the HFHFr microbiota was monodominated by Cupriavidus. In parallel, the PA profile was significantly altered in the HFHFr group compared to controls with decreased levels of 3-OH-benzoic acid, 4-OH-benzoic acid, isoferulic acid and ferulic acid at 6 h of WW fermentation. In pancreatic beta cells, exposure to pre-fermentation supernatants led to inhibition of insulin release, which was reversed over fermentation time. We conclude that HFHFr mice as a model of T2D are characterized by a dysbiotic microbiota, which is modulated by the in vitro fermentation of WW. The differences in microbiota composition have implications for PA profile dynamics and for the secretory capacity of pancreatic beta cells.

Curcumin nanoemulsion counteracts hepatic and cardiac complications associated with high-fat/high-fructose diet in rats.

The relationship between the incidence of cardiovascular abnormalities and non-alcoholic fatty liver disease (NAFLD) has long been postulated. Curcumin (CUR) is a potential anti-atherosclerotic agent but its poor water solubility hinders its pharmacological use. Therefore, the present study aimed to investigate the effect of formulation of CUR nanoemulsion prepared using the spontaneous emulsification technique on high fat high fructose (HFHF)-induced hepatic and cardiac complications. Fifty Wistar rats were divided into five groups. CUR nanoemulsion at doses of 5 and 10mg/kg and conventional powdered CUR at a dose of 50 mg/kg were orally administered daily to rats for two weeks, and compared with normal control and HFHF control. Results revealed that the high dose level of CUR nanoemulsion was superior to conventional CUR in ameliorating the HFHF-induced insulin resistance status and hyperlipidemia, with beneficial impact on rats' recorded electrocardiogram (ECG), serum aspartate aminotransferase (ALT) and alanine aminotransferase (AST) levels, leptin, adiponectin, creatine phosphokinase, lactate dehydrogenase and cardiac troponin-I. In addition, hepatic and cardiac oxidative and nitrosative stresses, oxidative DNA damage and disrupted cellular energy statuses were counteracted. Results were also confirmed by histopathological examination. PRACTICAL APPLICATIONS: The use of curcumin nanoemulsion could be beneficial in combating hepatic and cardiac complications resulting from HFHF diets.