High Fat Fructose Research Articles

Effects of probiotics and high fructose diet on De Ritis ratio, TGF-B levels, and liver histopathology of Sprague Dawley rats

Background: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Histopathological diagnosis has been the gold standard for diagnosing and determining the severity of non-alcoholic steatohepatitis (NASH). However, this method is invasive, especially for diagnosing NASH in children. This research aimed to study the effect of probiotics on the De Ritis ratio, TGF-β levels, and histopathological changes in rats given High Fat, High Fructose (HFHFr) diet to look at the correlation between the De Ritis ratio and liver histopathology in diagnosing NAFLD. Method: Twenty-one male Sprague Dawley rats were included and divided into three groups. In the first group, as control only received a normal chow diet for eight weeks. The second group received an HFHFr diet for eight weeks, and the last group received HFHFr for eight weeks and a combination of HFHFr and probiotics for another eight weeks. After decapitation, we took 3 ml of serum from each rat to measure AST, ALT, and TGF-β. A 4 μm thick liver tissue slide was taken and stained with Hematoxylin – Eosin Stain for histopathological analysis. We used the Non-Alcoholic Steatohepatitis (NAS) Score for measuring liver damage progression. Results: De Ritis ratio and TGF-β level did not significantly differ between probiotic and non-probiotic groups (p = 0.064 and 0.383), but there was a significant NAS score difference (p = 0.001) in probiotic and non-probiotic groups. This was followed by a significant correlation between the De Ritis ratio and the NAS score (r = 0.613, p = 0.003). Conclusion: Probiotic supplementation alleviated liver damage caused by the HFHFr diet but did not successfully reduce the De Ritis ratio or improve TGF-β.

Effect of Aronia melanocarpa fruit juice on glucose tolerance, lipid metabolism, and obesity in a rat model of metabolic syndrome

Abstract Metabolic syndrome (MS) is a serious health condition. The purpose of this study was to investigate the effects of polyphenol-rich Aronia melanocarpa fruit juice (AMFJ) on glucose tolerance, triglyceride levels, and adipose tissue in rats with MS induced by high-fat high-fructose (HFHF) diet. Fifty rats were allocated in 5 groups: control, MS, MS+AMFJ2.5, MS+AMFJ5, and MS+AMFJ10. In the course of 10 weeks, the control group was on a regular rat diet while the other groups received HFHF diet. During the experiment, control and MS groups were treated daily orally with distilled water (10.0 mL kg−1) and the other three groups – with AMFJ at doses of 2.5, 5.0, and 10.0 mL kg−1, respectively. In MS rats, glucose intolerance, hypertriglyceridemia, visceral obesity, and increased adipocyte size were observed. In AMFJ-treated groups, the serum glucose and triglycerides, as well as visceral fat and adipocyte size decreased significantly and did not differ from those of the control group. AMFJ at doses 2.5 and 5.0 mL kg−1 showed an anti-apoptotic activity in adipocytes, while at the dose of 10 mL kg−1 a pro-apoptotic effect was detected. In conclusion, AMFJ could antagonise most of the negative consequences of HFHF diet on carbohydrate and lipid metabolism in a rat MS model.

The effects of the voglibose on non-alcoholic fatty liver disease in mice model

The α-glucosidase inhibitor (α-GI) delays the intestinal absorption of glucose, which reduces postprandial hepatic glucose intake. This mechanism is considered to be effective in treating non-alcoholic fatty liver disease (NAFLD). Here, we investigated the effect of voglibose, an α-glucosidase inhibitor, on high-fat, high-fructose (HFHFr) diet-induced NAFLD models. Seven-week-old male C57BL/6J mice were randomly placed in a chow diet group or an HFHFr diet group. After 10 weeks, mice in the HFHFr group were randomly assigned to one of three groups: HFHFr diet with vehicle, HFHFr with voglibose, or HFHFr with pioglitazone. Each diet and treatment was continued for 10 weeks. The HFHFr diet induced severe NAFLD in terms of steatosis, hepatitis, and fibrosis. Administration of voglibose improved all aspects of NAFLD, comparable to those of pioglitazone, a positive control. In voglibose-treated mice, gene expressions of hepatic lipogenesis markers were significantly downregulated. In the in vitro experiment, reducing the influx of glucose into hepatocytes significantly reduced steatosis and de novo lipogenesis even in the presence of sufficient fructose and fat, demonstrating that the mechanism of voglibose could be effective in treating HFHFr diet-induced NAFLD. These results indicate that voglibose improves HFHFr diet-induced NAFLD by suppressing hepatic de novo lipogenesis.

Evaluation of the toxicology, anti-lipase, and antioxidant effects of Callistemon citrinus in rats fed with a high fat-fructose diet

Context Callistemon citrinus Skeels (Myrtaceae) exhibits many biological activities. Objective This study analyzes for the first time, the toxicity, obesogenic, and antioxidant effects of C. citrinus in rats fed with a high fat-fructose diet (HFFD). Materials and methods Four studies using male Wistar rats were conducted: (a) 7 groups (n = 3): control (corn oil) and ethanol extract of C. citrinus leaf (single oral dose at 100–4000 mg/kg) for acute toxicity; (b) 2 groups (n = 8): control (corn oil) and C. citrinus (1000 mg/kg/day) for 28 days for subacute toxicity; (c) 3 groups (n = 4) with single oral dose of lipid emulsion: control (lipid emulsion), C. citrinus and orlistat (250 and 50 mg/kg, respectively) for lipid absorption; (d) 4 groups (n = 6): control (normal diet) and 3 groups fed with HFFD: HFFD only, C. citrinus and simvastatin (oral dose 250 and 3 mg/kg, respectively) for 13 weeks. Antioxidant enzymes and biomarkers were evaluated and inhibition of pancreatic lipase was determined in vitro. Results Toxicological studies of C. citrinus showed no differences in biochemical parameters and lethal dose (LD50) was higher than 4000 mg/kg. C. citrinus inhibited pancreatic lipase activity, with IC50 of 392.00 µg/mL, and decreased lipid absorption by 70%. Additionally, it reduced the body weight 22%, restored the activities of antioxidant enzymes, and reduced the biomarkers of oxidative stress. Conclusions Callistemon citrinus showed an effect against oxidative stress by reducing biomarkers and induced antioxidant system, without toxic effects.

Moroccan pomegranate (sefri variety) polyphenols prevent hyperlipidemia, oxidative stress and enhance cholesterol efflux processes

Background and Aims : The present study aimed to investigate the effect of phenolic-rich extract from pomegranate peels (PEPP) and arils (PEPA) on lipid profile in high fat-high fructose diet (HFFD) induced hyperlipidemia in Wistar rats and to provide a molecular explanation for their effects.

Sargassum fusiforme fucoidan ameliorates diet-induced obesity through enhancing thermogenesis of adipose tissues and modulating gut microbiota

Obesity has become a global epidemic. Sargassum fusiforme fucoidan (Fuc) is a group of water-soluble heteropolysaccharides that exhibits a wide range of medicinal functions. It consists of l-fucose and sulfate groups, with l-fucose as the main monosaccharide. This study investigated the therapeutic effects of Fuc on diet-induced obesity (DIO) in C57BL/6J female mice. Fuc significantly alleviated obesity in mice induced by high-fat high-fructose (HFHF) feeding, inhibiting body weight gain, reducing fat accumulation, and improving hepatic steatosis. In addition, Fuc significantly improved glucose tolerance and insulin sensitivity by enhancing the phosphorylation level of AKT (at Ser473) in the adipose tissues. Mechanistically, although Fuc did not decrease the energy intake in DIO mice, it significantly increased the energy expenditure by up-regulating the expression of uncoupling protein 1 (UCP1) in the adipose tissues. Notably, Fuc also improved the obesity-driven dysbiosis of gut microbiota and decreased the relative abundance of the obesity-related intestinal bacteria. However, Fuc was unable to alleviate DIO-induced metabolic disorders in pseudo-sterile mice. Our findings suggested that Fuc might remodel gut microbiota and exert its weight loss and hypolipidemic effects by increasing the energy expenditure, thus providing a novel perspective for treating obesity and related complications.

Punicalagin Alleviates Oxidative Stress and Pathological Changes in Brain of Mice-Fed High Fat, High Fructose Diet

The present study investigated to know whether the pomegranate polyphenol punicalagin (PU) can ameliorate oxidative stress and pathological alterations induced by a calorie rich diet comprised of fat and fructose. Male Swiss albino mice were fed normal pellet (Control) or high fat-high fructose diet (HFFD) for 60 days. PU (30 or 60 mg/kg bw) was administered orally for the last 15 days for both dietary groups. Measurement of TBARS, AOPP and FRAP in plasma, histopathology of liver and brain, assessment of oxidative damage in brain tissues, and blood brain barrier function were carried out. HFFD mice showed an increase in the levels of TBARS and AOPP, and a decline in FRAP. PU administration to HFFD mice reduced the levels of TBARS and AOPP and improved FRAP significantly. Histopathology results showed fatty changes and inflammatory infiltration in the liver of HFFD mice. Cortex and hippocampus of HFFD mice confirmed the presence of degenerating neurons with shrunken cytoplasm and pyknotic nuclei. PU treatment caused significant hepato and neuroprotective effects, and among the two doses the high dose of PU (60 mg/kg) showed more pronounced effects than the low dose (30 mg/kg). The immunohistochemical localization of the markers of oxidative damage to proteins (3-NT), lipids (4-HNE) and DNA (8-OHG) was increased in brain tissues of HFFD mice and upon PU administration (60 mg/kg) the levels of these oxidative stress markers were significantly decreased. Our findings clearly suggest that PU can modulate oxidative stress and could be a potential candidate for treating neurodegenerative processes associated with calorie excess.

The Role of a High-Fat, High-Fructose Diet on Letrozole-Induced Polycystic Ovarian Syndrome in Prepubertal Mice.

This study aims to investigate the effects of a high-fat, high-fructose (HF/HFr) diet on metabolic/endocrine dysregulations associated with letrozole (LET)-induced Polycystic Ovarian Syndrome (PCOS) in prepubertal female mice. Thirty-two prepubertal C57BL/6 mice were randomly divided into four groups of eight and implanted with LET or a placebo, with simultaneous administration of an HF/HFr/standard diet for five weeks. After sacrifice, the liver and blood were collected for selected biochemical analyses. The ovaries were taken for histopathological examination. The LET+HF/HFr group gained significantly more weight than the LET-treated mice. Both the LET+HF/HFr and the placebo-treated mice on the HF/HFr diet developed polycystic ovaries. Moreover the LET+HF/HFr group had significantly elevated testosterone levels, worsened lipid profile and indices of insulin sensitivity. In turn, the HF/HFr diet alone led to similar changes in the LET-treated group, except for the indices of insulin sensitivity. Hepatic steatosis also occurred in both HF/HFr groups. The LET-treated group did not develop endocrine or metabolic abnormalities, but polycystic ovaries were seen. Since the HF/HFr diet can cause substantial metabolic and reproductive dysregulation in both LET-treated and placebo mice, food items rich in simple sugar—particularly fructose—and saturated fat, which have the potential to lead to PCOS progression, should be eliminated from the diet of young females.

Paricalcitol Attenuates Metabolic Syndrome-Associated Heart Failure through Enhanced Mitochondrial Fusion.

Objectives Transition from cardiac hypertrophy to failure involves adverse metabolic reprogramming involving mitochondrial dysfunction. We have earlier shown that vitamin D deficiency induces heart failure, at least in part, through insulin resistance. However, whether activation of vitamin D receptor (VDR) can attenuate heart failure and underlying metabolic phenotype requires investigation. Thus, we aimed to assess the cardioprotective potential of paricalcitol, a vitamin D receptor-activator, against cardiac hypertrophy and failure in high-fat high-fructose-fed rats. Methods Male Sprague Dawley rats were fed control (Con) or high-fat high-fructose (HFHFrD) diet for 20 weeks. After 12 weeks, rats from HFHFrD group were divided into the following: HFHFrD, HFHFrD+P (paricalcitol i.p. 0.08 μg/kg/day) and HFHFrD+E (enalapril maleate i.p. 10 mg/kg/day). Intraperitoneal glucose tolerance test, blood pressure measurement, and 2D echocardiography were performed. Cardiac fibrosis was assessed by Masson's trichrome staining of paraffin-embedded heart sections. Mitochondrial DNA and proteins, and citrate synthase activity were measured in rat hearts. VDR was silenced in H9c2 cardiomyoblasts, and immunoblotting was performed. Results Paricalcitol improved glucose tolerance, serum lipid profile, and blood pressure in high-fat high-fructose-fed rats. Paricalcitol reduced cardiac wall thickness and increased ejection fraction in high-fat high-fructose-fed rats but had no effect on perivascular fibrosis. PGC1-α was upregulated in the HFHFrD+P group compared to the HFHFrD group, but there was no significant difference in mitochondrial content. Citrate synthase activity was significantly higher in the HFHFrD+P group compared to the HFHFrD group. Rat hearts of the HFHFrD+P group had significantly higher expression of mitofusins. H9c2 cells with VDR knockdown showed significantly lower expression of Mfn2. Improvement in the HFHFrD+P group was comparable with that in the HFHFrD+E group. Conclusions Paricalcitol reverses cardiac dysfunction in rats with metabolic syndrome by enhancing mitochondrial fusion. We demonstrate repurposing potential of the drug currently used in end-stage kidney disease.

Fenofibrate Improves Cognitive Impairment Induced by High-Fat High-Fructose Diet: A Possible Role of Irisin and Heat Shock Proteins.

A high-fat, high-fructose diet (HFFD) impairs cognitive functions and increases susceptibility to neurodegenerative disorders. Irisin and heat shock protein 70 (HSP70) are well known for their role in neuroprotection. The possible neuroprotective effects of fenofibrate on HFFD-induced cognitive dysfunction and the involvement of irisin and HSP70 in these effects were investigated in this study. Rats were divided into normal control, HFFD, dimethylsulfoxide+HFFD, and fenofibrate+HFFD groups. At the end of the experiment, fenofibrate treatment restored hippocampus histological characteristics to almost normal and improved HFFD-induced cognitive deficit. It reduced body weight gain and had hypolipidemic effects by significantly lowering total cholesterol, triglycerides, and low-density lipoprotein cholesterol levels while increasing high-density lipoprotein cholesterol levels. It has antioxidant and anti-inflammatory effects as it significantly reduced the hippocampal malondialdehyde, interleukin-6, and tumor necrosis factor-alpha levels, while significantly increasing the reduced glutathione level. It prevented HFFD-induced hypoxia by significantly lowering hippocampal vascular endothelial growth factor and hypoxia-inducible factor-1 alpha levels. It significantly activated the hippocampal peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α)/irisin/brain-derived neurotrophic factor pathway. It significantly increased hippocampal HSP70 while decreasing the HSP90 levels. It enhanced synaptic plasticity by significantly upregulating the hippocampal relative GluR1 gene expression. Furthermore, hippocampal irisin levels in the HFFD group were found to be positively correlated with cognitive function, hippocampal HSP70, and relative GluR1 gene expression levels, while negatively correlated with hippocampal HSP90 and HIF1α levels. Therefore, fenofibrate may be used as a potential medication to treat HFFD-induced neurodegenerative disorders.

Nil-Surin Rice Bran Hydrolysates Improve Lipid Metabolism and Hepatic Steatosis by Regulating Secretion of Adipokines and Expression of Lipid-Metabolism Genes

Overconsumption of a high caloric diet is associated with metabolic disorders and a heightened risk of diabetes mellitus (DM), hepatic steatosis, and cardiovascular complications. The use of functional food has received much attention as a strategy in the prevention and treatment of metabolic disorders. This present study investigated whether Nil-Surin rice bran hydrolysates (NRH) could prevent or ameliorate the progression of metabolic disorders in rats in which insulin resistance (IR) was induced by a high fat-high fructose diet (HFFD). After 10 weeks of the HFFD, the rats showed elevated fasting blood glucose (FBG), impaired glucose tolerance, dysregulation of adipokine secretion, distorted lipid metabolism such as dyslipidemia, and increased intrahepatic fat accumulation. The IR was significantly attenuated by a daily dose of NRH (100 or 300 mg/kg/day). Doses of NRH rectified adipokine dysregulation by increasing serum adiponectin and improving hyperleptinemia. Interestingly, NRH decreased intrahepatic fat accumulation and improved dyslipidemia as shown by decreased levels of hepatic triglyceride (TG) and serum TG, total cholesterol and low-density lipoprotein cholesterol, and increased high-density lipoprotein cholesterol. In addition, a modulation of expression of lipid metabolism genes was observed: NRH prevented upregulation of the lipogenesis genes Srebf1 and Fasn. In addition, NRH enhanced the expression of fatty-acid oxidation genes, as evidenced by an increase of Ppara and Cpt1a when compared with the HFFD control group. The activities of NRH in the modulation of lipid metabolism and rectifying the dysregulation of adipokines may result in a decreased risk of DM and hepatic steatosis. Therefore, NRH may be beneficial in ameliorating metabolic disorders in the HFFD model.

Long-Term High-Fat High-Fructose Diet Induces Type 2 Diabetes in Rats through Oxidative Stress.

Long-term consumption of a Western diet is a major cause of type 2 diabetes mellitus (T2DM). However, the effects of diet on pancreatic structure and function remain unclear. Rats fed a high-fat, high-fructose (HFHF) diet were compared with rats fed a normal diet for 3 and 18 months. Plasma biochemical parameters and inflammatory factors were used to reflect metabolic profile and inflammatory status. The rats developed metabolic disorders, and the size of the islets in the pancreas increased after 3 months of HFHF treatment but decreased and became irregular after 18 months. Fasting insulin, C-peptide, proinsulin, and intact proinsulin levels were significantly higher in the HFHF group than those in the age-matched controls. Plasmatic oxidative parameters and nucleic acid oxidation markers (8-oxo-Gsn and 8-oxo-dGsn) became elevated before inflammatory factors, suggesting that the HFHF diet increased the degree of oxidative stress before affecting inflammation. Single-cell RNA sequencing also verified that the transcriptional level of oxidoreductase changed differently in islet subpopulations with aging and long-term HFHF diet. We demonstrated that long-term HFHF diet and aging-associated structural and transcriptomic changes that underlie pancreatic islet functional decay is a possible underlying mechanism of T2DM, and our study could provide new insights to prevent the development of diet-induced T2DM.

The ameliorative effect of Apium graveolens & curcumin against Non-alcoholic fatty liver disease induced by high fructose-high fat diet in rats

BackgroundNon-alcoholic fatty liver disease (NAFLD) is a condition resulting from fat aggregates in liver cells and is associated with metabolic syndrome, obesity, and oxidative stress. The present work was designed to investigate the role of celery and curcumin against high-fructose–high-fat (HFHF) diet-induced NAFLD in rats. Thirty male rats were classified into five groups: GP1: control group (rats were fed a normal control diet), GP2: HFHF group as a positive control (rats were fed a HFHF diet) for 20 weeks, GP3: HFHF + sily group, GP4: HFHF + celery group, and GP5: HFHF + cur group (rats in 3, 4, and 5 were treated as in the HFHF group for 16 weeks, then combined treatment daily by gavage for 4 weeks with either silymarin (as a reference drug, 50 mg/kg bw) or celery (300 mg/kg bw) or curcumin (200 mg/kg bw), respectively. The progression of NAFLD was evaluated by estimating tissue serum liver enzymes, glycemic profile, lipid profile, oxidative stress markers in liver tissue, and histopathological examination. Moreover, DNA fragmentation and the released lysosomal enzymes (acid phosphatase, β-galactosidase, and N-acetyl-B-glucosaminidase) were estimated.ResultsOur results showed that HFHF administration for 16 weeks caused liver enzymes elevation, hyperglycemia, and hyperlipidemia. Furthermore, increased hepatic MDA levels along with a decline in GSH levels were observed in the HFHF group as compared to the control group. The results were confirmed by a histopathological study, which showed pathological changes in the HFHF group. DNA fragmentation was also observed, and the lysosomal enzyme activities were increased. On the other hand, oral supplementation of celery and cur improved all these changes compared with positive control groups and HFHF + sily (as a reference drug). Moreover, celery, as well as curcumin co-treatment, reduced HFHF-enhanced DNA fragmentation and inhibited elevated lysosomal enzymes. The celery combined treatment showed the most pronounced ameliorative impact, even more than silymarin did.ConclusionOur findings suggest that celery and curcumin consumption may exhibit ameliorative impacts against NALFD progression, while celery showed more ameliorative effect in all parameters.

Label free DIA and DDA nano‐LC/MS/MS improved quantitative profiling of redox stress mediated proteomic changes in mouse dendritic cells

A diet rich in saturated fat and carbohydrates causes a low‐grade chronic inflammation in several organs. To investigate the impact of oxidative stress and metabolic syndrome on the whole cellular proteome of professional antigen presenting cells (APCs), we isolated six biological replicates consisted of total proteomic extracts of dendritic cells (DCs) from B6 mice on normal and high fructose/high fat (HFHF) diet and performed quantitative label‐free data independent (DIA) and data dependent (DDA) nano LC‐MS/MS analysis of protein expression profiles. Our optimized primary DCs processing for label free proteomics and DIA quantitative analysis retrieved 1451 proteins (with at least 1 unique peptide), identified at 2% attained FDR (0.5% FDR for peptides) out of which 744 proteins were eligible for quantitative analysis and exhibited statistically significant changes in mouse DCs proteomes harvested from mice on HFHF vs normal diet (ANOVA, p<0.05). Bioinformatics and GO annotations mapped quantitative changes in energy and stress related proteins associated with several metabolic pathways including glycolysis, lipolysis and mitochondrial oxidative phosphorylation, reflecting the possible onset of insulin‐resistance phenotype. The (LFQ) DIA analysis highlighted qualitative and quantitative changes in the proteomes from mouse DCs, spanning a wide spectrum of up‐regulated inflammatory pathways, which in turn, could wire the reshaping of immunopeptidome landscape presented by MHC‐II under redox metabolic stress.

Effect Soursop (Annona muricata L.) Leaf Aqueous Extract (SLAE) on Remodeling of Ventricle Heart Tissue in Obesity Rats Model

A high-fat and high-fructose diet can lead to obesity which contributes to an increased risk of heart failure complications. Soursop leaves are known to have the potential of antioxidant, but research about the effects of soursop leaf on complications of heart failure has never been studied. This study evaluated whether soursop leaf aqueous extract can inhibit the total of cardiomyocyte necrosis, cardiomyocyte diameter, and density of cardiac collagen in obese rats. The heart organs of obese rats that have been paraffin, which randomly divided into normal group, obesity group, and soursop leaf aqueous extract (SLAE) group with dose I (100 mg/kgbw), II (200 mg/kgbw), and III (400 mg/kgbw) (n=6 rats). The rats were induced by high-fat high-fructose and SLI diets for 10 weeks. The number of necrosis and diameter cardiomyocytes were measured by using Hematoxylin Eosin staining, while the density of cardiac collagen was measured by Masson's Trichrome staining and then observed with a trinocular and dot side microscope at 200x and 400x magnification. Statistical analysis using One Way ANOVA and continued by LSD test. We found that group SLAE with doses I, II, and III significantly reduced the number of cardiomyocyte necrosis and cardiac collagen density compared to the obesity group. The SLI group with doses II and III significantly reduced the diameter of cardiomyocytes compared to the obesity group, while the SLAE group with the dose I was unable to reduce the diameter of cardiomyocytes. In conclusion, Soursop leaf aqueous extract can inhibit the increase of cardiac collagen density, number necrosis and diameter cardiomyocyte.

A High-Fat High-Fructose Diet Dysregulates the Homeostatic Crosstalk Between Gut Microbiome, Metabolome, and Immunity in an Experimental Model of Obesity.

Ample evidence supports the prominent role of gut-liver axis in perpetuating pathological networks of high-fat high-fructose (HFF) diet induced metabolic disorders, however, the molecular mechanisms are still not fully understood. Herein, this study aims to present a holistic delineation and scientific explanation for the crosstalk between the gut and liver, including the potential mediators involved in orchestrating the metabolic and immune systems. An experimental obesity-associated metaflammation rat model is induced with a HFF diet. An integrative multi-omics analysis is then performed. Following the clues illustrated by the multi-omics discoveries, putative pathways are subsequently validated by RT-qPCR and Western blotting. HFF diet leads to obese phenotypes in rats, as well as histopathological changes. Integrated omics analysis shows that there exists a strong interdependence among gut microbiota composition, intestinal metabolites, and innate immunity regulation in the liver. Some carboxylic acids may contribute to gut-liver communication. Moreover, activation of the hepatic LPS-TLR4 pathway in obesity is confirmed. HFF-intake disturbs gut flora homeostasis. Crosstalk between gut microbiota and innate immune system mediates hepatic metaflammation in obese rats, associated with LPS-TLR4 signaling pathway activation. Moreover, α-hydroxyisobutyric acid and some other organic acids may play a role as messengers in the liver-gut axis.

Quercetin-loaded on whey protein improves male fertility parameters and atherogenic indices of rats on a western-style diet

The western-style diet, characterized by high fat-high fructose (HF/HFr) intake, induces alteration in spermatogenesis and testicular functions by atherogenic indices derangement and oxidative stress. The antioxidant properties of Quercetin (Quer) are proved; however, it has some adverse effects on male fertility parameters. So, this study aimed to investigate the protective effect of a biocompatible carrier (whey protein coated with black seed oil) as a new drug delivery system to encapsulate the Quer on atherogenic indices, insulin sensitivity, sperm parameters, and testicular function alterations induced by a western-style diet in male rats. Abnormal testicular epithelium with detached and swelled germ cells, alterations in the ratio of the spermatogenic cells, increased percentage of apoptotic cells (TUNEL-positive), and abnormalities in sperm parameters were observed in the male rats on a western-style diet. Treated groups with the free Pro-gel (whey protein gel) and Pro-gel-Quer (Quer loaded on whey protein gel) showed significant recovery of the germ cells and reduction in the TUNEL-positive cell number. There was a significant increase in the atherogenic index TG/HDL-C, serum FBS, insulin, and HOMA-IR, but the decrease in testosterone levels in the model groups (p < 0.05). However, these parameters reached near to the control in the Pro-gel-Quer-treated one compared with the free Quer and Pro-gel groups. Nutritional transition to the HF-HFr diets has deleterious effects on the testicular function and sperm parameters. Quer, as an antioxidant, loaded on whey protein is a new biocompatible antioxidant-therapy in male fertility and lipid profile complications induced by the western-style diet.

Involvement of microbiota and short-chain fatty acids on non-alcoholic steatohepatitis when induced by feeding a hypercaloric diet rich in saturated fat and fructose.

Consumption of high-energy-yielding diets, rich in fructose and lipids, is a factor contributing to the current increase in non-alcoholic fatty liver disease prevalence. Gut microbiota composition and short-chain fatty acids (SCFAs) production alterations derived from unhealthy diets are considered putative underlying mechanisms. This study aimed to determine relationships between changes in gut microbiota composition and SCFA levels by comparing rats featuring diet-induced steatohepatitis with control counterparts fed a standard diet. A high-fat high-fructose (HFHF) feeding induced higher body, liver and mesenteric adipose tissue weights, increased liver triglyceride content and serum transaminase, glucose, non-HDL-c and MCP-1 levels. Greater liver malondialdehyde levels and glutathione peroxidase activity were also observed after feeding the hypercaloric diet. Regarding gut microbiota composition, a lowered diversity and increased abundances of bacteria from the Clostridium sensu stricto 1, Blautia, Eubacterium coprostanoligenes group, Flavonifractor, and UBA1819 genera were found in rats featuring diet-induced steatohepatitis, as well as higher isobutyric, valeric and isovaleric acids concentrations. These results suggest that hepatic alterations produced by a hypercaloric HFHF diet may be related to changes in overall gut microbiota composition and abundance of specific bacteria. The shift in SCFA levels produced by this unbalanced diet cannot be discarded as potential mediators of the reported hepatic and metabolic alterations.

Atorvastatin with Lactobacillus rhamnosus supplementation Ameliorates Pathogenesis of High fat-High fructose diet induced non-alcoholic fatty liver disease in rats

Non-alcoholic fatty liver disease (NAFLD) is a broad term that includes anything from simple adipose tissue deposition in the liver to more advanced steatosis with concomitant hepatitis, fibrosis, and cirrhosis. The incidence of NAFLD is predicted to rise because of the increased prevalence of related disorders such as obesity and type 2 diabetes mellitus (T2DM). All statins seem to be successful in decreasing patients' cholesterol levels with NAFLD, while there is greater experience with atorvastatin, the only statin that has been shown to reduce the risk of cardiovascular events in these individuals. Atorvastatin, like other statins, acts by blocking HMG-CoA reductase, an enzyme located in liver tissue that is important in the production of cholesterol in the body. But Atorvastatin's primary adverse impact is a loss of muscle and an accelerated breakdown of muscular tissue (rhabdomyolysis). Certain probiotic lactobacilli strains offer positive benefits, most likely via anti-inflammatory activities and intestinal barrier stability, which reduces liver diseases. The present study's goal is to see how Atorvastatin at a subtherapeutic dosage combined with a probiotic strain, Lactobacillus rhamnosus, affects male SD rats in the treatment of NAFLD.

L-Methionine supplementation attenuates high-fat fructose diet-induced non-alcoholic steatohepatitis by modulating lipid metabolism, fibrosis, and inflammation in rats.

Recently, the protective effects of a methionine-rich diet on hepatic oxidative stress and fibrosis have been suggested but not adequately studied. We, therefore, hypothesized that L-methionine supplementation would ameliorate the progression of hepatic injury in a diet-induced non-alcoholic steatohepatitis (NASH) model and aimed to investigate the underlying mechanism. NASH was developed in male Sprague Dawley rats by feeding them with a high-fat-fructose diet (HFFrD) for 10 weeks. The results demonstrated that L-methionine supplementation to NASH rats for 16 weeks improved the glycemic, lipid, and liver function profiles in NASH rats. Histological analysis of liver tissue revealed a remarkable improvement in the three classical lesions of NASH: steatosis, inflammation, and ballooning. Besides, L-methionine supplementation ameliorated the HFFrD-induced enhanced lipogenesis and lipid peroxidation. An anti-inflammatory effect of L-methionine was also observed through the inhibition of the release of proinflammatory cytokines. Furthermore, the hepatic SIRT1/AMPK signaling pathway was associated with the beneficial effects of L-methionine. This study demonstrates that L-methionine supplementation in HFFrD-fed rats improves their liver pathology via regulation of lipogenesis, inflammation, and the SIRT1/AMPK pathway, thus encouraging its clinical evaluation for the treatment of NASH.