High-fat And High-fructose Diet Research Articles

Dedicator of Cytokinesis 2 (DOCK2) Deficiency Attenuates Lung Injury Associated with Chronic High-Fat and High-Fructose Diet–Induced Obesity

Obesity is a major risk factor for lung disease development. However, little is known about the impact of chronic high-fat and high-fructose (HFHF) diet-induced obesity on lung inflammation and subsequent pulmonary fibrosis. Herein we hypothesized that dedicator of cytokinesis 2 (DOCK2) promotes a proinflammatory phenotype of lung fibroblasts (LFs) to elicit lung injury and fibrosis in chronic HFHF diet-induced obesity. An HFHF diet for 20 weeks induced lung inflammation and profibrotic changes in wild-type C57BL/6 mice. CD68 and monocyte chemoattractant protein-1 (MCP-1) expression were notably increased in the lungs of wild-type mice fed an HFHF diet. An HFHF diet further increased lung DOCK2 expression that co-localized with fibroblast-specific protein 1, suggesting a role of DOCK2 in regulating proinflammatory phenotype of LFs. Importantly, DOCK2 knockout protected mice from lung inflammation and fibrosis induced by a HFHF diet. In primary human LFs, tumor necrosis factor-α (TNF-α) and IL-1β induced DOCK2 expression concurrent with MCP-1, IL-6, and matrix metallopeptidase 2. DOCK2 knockdown suppressed TNF-α-induced expression of these molecules and activation of phosphatidylinositol 3-kinase/AKT and NF-κB signaling pathways, suggesting a mechanism of DOCK2-mediated proinflammatory and profibrotic changes in human LFs. Taken together, these findings reveal a previously unrecognized role of DOCK2 in regulating proinflammatory phenotype of LFs, potentiation of lung inflammation, and pulmonary fibrosis in chronic HFHF diet-caused obesity.

Chia Sprouts Elicitation with Salicylic Acid and Hydrogen Peroxide to Improve their Phenolic Content, Antioxidant Capacities In Vitro and the Antioxidant Status in Obese Rats.

Elicitation is a biotechnological approach to improve phenolic compounds content and antioxidant properties of ready-to-eat functional foods. This study aimed to evaluate the chemical elicitation effects using salicylic acid (SA) and hydrogen peroxide (H2O2) in optimized-germination conditions on seedling vigor, phenolic content, and their antioxidant capacities in vitro and serum and urine of Wistar obese rats. Optimized-germination conditions of 26.5°C and 178h produced a 64% of germination and a sprout length of 56mm. Only, the elicitation with H2O2 (20mM) enhanced the germination (75%) and H2O2 (10 and 20mM) the sprout length (69 and 59mm, respectively). In contrast, both elicitors enhanced phenolic contents, being more significant total phenolic compounds content for SA (1 and 2mM), up to 65.5-73.5%. SA and H2O2 improved total flavonoids content (36.5-64.1%), ABTS (19.3-61.1%), and DPPH capacities (51-86%), depending on SA and H2O2 concentration, compared with non-elicited chia sprouts. The QUENCHER antioxidant capacities of elicited chia sprouts increased up to three times more than extracts capacities, principally Q-ABTS, which could be attributed to phenolic bounds to dietary fiber. Rats fed with a high-fat and fructose diet (HFFD) and supplemented with chia sprouts, especially 1-mM SA, improve the obesity-related oxidative stress through an increase of antioxidant capacities, using DPPH and ABTS test, on serum (70-118%) and urine samples (80-116%). These results suggest that chia sprouts elicited with 1-mM SA are a source of antioxidant compounds that can be used to decrease obesity related oxidative stress.

Beet (Beta vulgaris) Suppressed Gene Expression and Serum Fatty Acid Synthase in High Fat and Fructose-induced Rats

BACKGROUND: The expression and activity of fatty acid synthase (FAS) enzymes determine de novo fatty acid synthesis, which can be enhanced by a high-fat and high fructose diet or inhibited by some bioactive compound diets. Beets are a great source of therapeutic compounds that have the potential to improve health and prevent disease. AIM: This study examined the effects of beets on liver FAS gene expression and FAS levels. METHODS: A total of 25 male Wistar rats divided into five groups: (1) Standard diet (n); (2) high fat and fructose diet (HFFD); (3) HFFD have given beet 6%-contained standard diet (B1); (4) HFFD have given beet 9%-contained standard diet (B2), and (5) HFFD have given beet 12%-contained standard diet (B3). The HFFD was given to rats in the 2, 3, 4, and 5 group diets for 8 weeks? and then 3, 4, and 5 groups received beet-contained standard diet for 6 weeks. At the end of the intervention, FAS levels were measured (please specify where it was measured from) using the ELISA method, liver FAS gene expression was analyzed by quantitative polymerase chain reaction, and triglyceride (TG) levels were determined by the colorimetric method. RESULTS: The beet-substituted diet significantly suppressed the hepatic FAS gene expression and decreased the serum FAS levels in rats previously given HFFD (p < 0.05). The expression of the FAS gene showed a significant positive correlation with the levels of FAS serum (p < 0.05), and also with the hepatic TG levels but not significant (p > 0.05). Substitution of beet 9% in diet gives the best effect in hepatic FAS gene expression and the serum FAS levels. CONCLUSIONS: The diet contained beet 9% was seen as a necessary physiological dose to improve the effects of high-fat and diet fructose diet through suppressing FAS gene expression and a decreased serum FAS levels.

Impact of combined therapy of mesenchymal stem cells and sitagliptin on a metabolic syndrome rat model.

Emerging evidence suggests that mesenchymal stem cells (MSCs) have many anti-inflammatory and regenerative properties, which makes it a suitable candidate for the treatment of many diseases including metabolic syndrome (MetS). However, a major difficulty with stem cell therapy is to maintain cell viability, properties and function after implantation in vivo. This study aims to test the hypothesis that the combined therapy of MSCs and sitagliptin can effectively ameliorate MetS complications induced by high-fat and high-fructose diet (HFFD) in rats. Rats were fed either standard diet (Control group) or HFFD. After 3months, a group of HFFD animals was injected by a single dose of MSCs, another group received a daily oral dose of 10mg/kg b.w. of sitagliptin, and the third group received the combined therapy of MSCs + sitagliptin for 1 month. Both MSCs and sitagliptin restored insulin sensitivity and reduced the HOMA-IR value in HFFD rats. The hepatic IRS-1 and Akt at both gene and protein levels, as well as the hepatic protein levels of IR and GLUT4 were improved. Downregulation of CHOP and NF-κB and upregulation of hepatic HO-1 expression and activity were also reported. Although MSCs and sitagliptin as monotherapy lead to remarkable effects, the dual application revealed the best results. Interestingly, histological findings confirmed these protective effects of the combined therapy against MetS complications. Combined therapy of MSCs and sitagliptin can efficiently ameliorate the insulin resistance and promote the regeneration of hepatocytes in the metabolic syndrome rat model.

A high-fat and high-fructose diet lowers the cecal digesta's weight and short-chain fatty acid level of a Sprague-Dawley rat model.

This study aimed to analyze the effect of a high-fat and high-fructose diet (HFFD) on the digesta weight and shortchain fatty acid (SCFA) levels of cecal digesta in rats. This study was an experimental study with a posttest-only control group design with male Sprague-Dawley strain rats as the samples. A total of 36 rats were divided into two groups with normal diet (N) and modified HFFD. The data of energy intake, nutrients and fiber, body weight, Lee index, abdominal circumference, digesta weight, and SCFA levels of cecal digesta were collected. The results showed an 11.94% increase in body weights of rats with HFFD. The total energy intake of the HFFD group was significantly higher than that of N (p = 0.000). The fiber intake and cecal digesta weight in group N were higher than that in the HFFD group (p = 0.00 and p = 0.02, respectively). The concentrations of acetate, butyrate, propionate, and total SCFA in the N group were significantly higher than in the HFFD (p = 0.041,,p = 0.004, p = 0.040, p = 0.013, respectively). A significant negative relationship was observed between the abdominal circumference and cecal digesta concentration (p = 0.029; r = -0.529) and between the Lee index and the SCFA concentration of cecal digesta (p = 0.036, r = -0.206).

Protective effects of rice bran hydrolysates on heart rate variability, cardiac oxidative stress, and cardiac remodeling in high fat and high fructose diet-fed rats

Objective: To examine the ameliorative effect of rice bran hydrolysates (RBH) on metabolic disorders, cardiac oxidative stress, heart rate variability (HRV), and cardiac structural changes in high fat and high fructose (HFHF)-fed rats. Methods: Male Sprague-Dawley rats were daily fed either standard chow diet with tap water or an HFHF diet with 10% fructose in drinking water over 16 weeks. RBH (500 and 1 000 mg/kg/day) was orally administered to the HFHF-diet-fed rats during the last 6 weeks of the study period. At the end of the treatment, metabolic parameters, oxidative stress, HRV, and cardiac structural changes were examined. Results: RBH administration significantly ameliorated metabolic disorders by improving lipid profiles, insulin sensitivity, and hemodynamic parameters. Moreover, RBH restored HRV, as evidenced by decreasing the ratio of low-frequency to high-frequency power of HRV, a marker of autonomic imbalance. Cardiac oxidative stress was also mitigated after RBH supplementation by decreasing cardiac malondialdehyde and protein carbonyl, upregulating eNOS expression, and increasing catalase activity in the heart. Furthermore, RBH mitigated cardiac structural changes by reducing cardiac hypertrophy and myocardial fibrosis in HFHF-diet-fed rats. Conclusions: The present findings suggest that consumption of RBH may exert cardioprotective effects against autonomic imbalances, cardiac oxidative stress, and structural changes in metabolic syndrome.

The protective effects of red beetroot (Beta vulgaris l.) against oxidative stress in rats induced by high fat and fructose diet

Background: One of consequence high-fat and fructose diet is oxidative stress. Consumption of antioxidants from red beetroot may increase antioxidant defense.
 Objectives: This study aimed to evaluate red beetroot administration on improving antioxidant defense in rats induced high fat and fructose diet.
 Methods: A total 20 male Wistar rats were divided into 4 groups: 1) normal control group (N), received standard diet; 2) High fat and fructose diet (HF), received high fat and fructose diet (HFFD); 8 weeks induction with HFFD and received 9g red beetroot (BA); and combination of HFFD and 9g of red beetroot from beginning of the study (HFBA). At the end of the study the levels of circulatory oxidized LDL (ox-LDL) were determined using enzyme-linked immunosorbent assay (ELISA) method. Superoxide dismutase 2 (SOD2) and catalase (CAT) gene expressions were determined by quantitative polymerase chain reaction (qPCR) method.
 Results: Induction HFFD increased the levels of circulatory ox-LDL levels compared to normal control (10.00±0.29 vs 12.69±0.57). Administration of red beetroot for 6 weeks and combination HFFD with red beetroot during the study significantly decreased ox-LDL levels compared to high fat and fructose group (12.69±0.57 vs 9.66±0.46) and (12.69±0.57 vs 8.59±0.18), respectively. The decreased circulatory ox-LDL levels were found negatively correlated with upregulation SOD2 (r=-0.548; P=0.012) and CAT (r=-0.460; P=0.041) gene expression in the liver tissues.
 Conclusion: Administration of red beetroot may ameliorate oxidative stress in rats induced high-fat and fructose diet through increasing antioxidant defense.

Dietary Fresh and Boiled Mangkokan Leaves (Nothopanax Scutellarius) Normalized Body Weight, Serum Lipid Profile and Malondialdehyde in Metabolic Syndrome Rats

The antioxidant activity of Nothopanax scutellarius (Burm. f.) Merr, an edible plant, can prevent oxidative stress in metabolic syndrome (MetS). Thus, our research aimed to study the effect of dietary inclusion of fresh or boiled N. scutellarius on body weight and biochemical markers of Wistar rats with MetS. Twenty-four male Wistar rats were divided randomly into four groups, i.e., normal control group, high-fat-high-fructose diet (HFFD) group, fresh N. scutellarius (FNs) group, and boiled N. scutellarius (BNs) group. The normal control group was fed only a standard diet during the entire experiment. High-fat and high-fructose (HFHFr) diet accompanied with 20% fructose in drinking water to induce MetS was given to the HFFD, FNs, and BNs groups for 29 days. This was followed by a 29-day intervention diet in which standard normal diet, fresh N. scutellarius-containing standard diet, and boiled N. scutellarius-containing standard diet were given to the HFFD, FNs, and BNs groups, respectively. HFHFr diet significantly (p<0.05) raised fasting blood glucose (FBG), serum triglyceride, total cholesterol, LDL-cholesterol, and malondialdehyde (MDA), and significantly (p<0.05) reduced HDL-cholesterol. After 29 days on the intervention diet, serum triglycerides, total cholesterol, and LDL-cholesterol levels were found to decrease, and HDL-cholesterol levels were found to increase significantly (p<0.05). Thus, it can be concluded that dietary intake of N. scutellarius for 29 days can improve MetS components, i.e., FBG, serum lipid profile, and MDA, similar to those seen in rats on a normal control diet.

Erica multiflora extract rich in quercetin-3-O-glucoside and kaempferol-3-O-glucoside alleviates high fat and fructose diet-induced fatty liver disease by modulating metabolic and inflammatory pathways in Wistar rats

The wide morbidity of obesity has heightened interest in providing natural and safe compounds to maintain optimal health. The present study was designed to determine the chemical constituents and the effects of methanol leaf extract from Erica multiflora (M-EML) on mitigating high-fat and high-fructose diet (HFFD)-induced metabolic syndrome (MS).LC–MS/MS characterization of M-EML allowed the identification of 14 secondary metabolites and showed that quercetin-3-O-glucoside and kaempferol-3-O-glucoside were the main compounds of our extract. In the in vivo study, the oral administration of M-EML (250 mg/kg) during the last 4 weeks of the experimentation alleviated HFFD-induced obesity, insulin resistance (IR) and cardiovascular diseases. Thus, M-EML treatment significantly normalized body and liver weight, allowed to a sharp decline in plasma levels of TC, TG and LDL-c by 32%, 35% and 66%, respectively. Moreover, hepatic enzymes, total and direct bilirubin, lipase and uric acid levels have been diminished in treated group. Histopathology of the liver confirmed the changes induced by HFFD and the hepatoprotective effect of M-EML. The supply of M-EML reduced NO production and cellular lysosomal enzyme activity by 44% and 60%, respectively compared to HFFD. Besides, M-EML showed decreased pro-inflammatory cytokines levels (259.5±47.35 pg/ml and 56.08±1.56 pg/ml) of TNF-α and IL-6, respectively.In addition, M-EML reduced liver malondialdehyde (MDA) content and enhanced superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities. In contrast, these enzymatic activities have been disrupted in HFFD rats.Overall, M-EML prevented obesity through the modulation of metabolic syndrome, reducing inflammation and promoting antioxidant enzymes activities.

Synergistic Effects of Heat-Killed Kefir Paraprobiotics and Flavonoid-Rich Prebiotics on Western Diet-Induced Obesity.

The synergistic anti-obesity effect of paraprobiotic heat-killed lactic acid bacteria (HLAB) and prebiotics has not been studied. To determine the anti-obesity properties of prebiotic polyphenol-rich wine grape seed flour (GSF) and paraprobiotic HLAB, C57BL/6J mice were administered a high-fat and high-fructose diet (HFFrD) with 5% microcrystalline cellulose (CON), HFFrD supplemented with 2.5% GSF, HFFrD with orally administered HLAB, or HFFrD with a combination of GSF and orally administered HLAB (GSF+HLAB) for 8 weeks. Compared with the CON group, the GSF and HLAB groups both showed significant reductions in HFFrD-induced body weight gain and adipose tissue weights (p < 0.05). Interestingly, combined supplementation with GSF and HLAB revealed statistically significant synergistic effects on body weight gain, visceral adiposity, and plasma triacylglycerol concentrations (p < 0.05). The synergistic action was significantly related to a decreased adipocyte gene expression in fatty acid synthesis and inflammation metabolism. In conclusion, the combination of prebiotic GSF and paraprobiotic kefir HLAB is potentially useful, as natural food ingredients, in the prevention of obesity and obesity-related diseases, especially for immunocompromised individuals.

Hydrogen inhalation alleviates nonalcoholic fatty liver disease in metabolic syndrome rats.

Hydrogen exhibits therapeutic and preventive effects against various diseases. The present study investigated the potential protective effect and dose-dependent manner of hydrogen inhalation on high fat and fructose diet (HFFD)-induced nonalcoholic fatty liver disease (NAFLD) in Sprague-Dawley rats. Rats were randomly divided into four groups: i) Control group, regular diet/air inhalation; ii) model group, HFFD/air inhalation; iii) low hydrogen group, HFFD/4% hydrogen inhalation; and iv) high hydrogen group, HFFD/67% hydrogen inhalation. After a 10-week experiment, hydrogen inhalation ameliorated weight gain, abdominal fat index, liver index and body mass index of rats fed with HFFD and lowered the total area under the curve in an oral glucose tolerance test. Hydrogen inhalation also ameliorated the increase in liver lipid content and alanine transaminase and aspartate transaminase activities. Liver histopathologic changes evaluated with hematoxylin and eosin as well as Oil Red O staining revealed lower lipid deposition in hydrogen inhalation groups, consistent with the decrease in the expression of the lipid synthesis gene SREBP-1c. The majority of the indicators were affected following treatment with hydrogen in a dose-dependent manner. In conclusion, hydrogen inhalation may play a protective role by influencing the general state, lipid metabolism parameters, liver histology and liver function indicators in the rat model of metabolic syndrome with NAFLD.

Effect of different fractions of chia (Salvia hispanica L.) on glucose metabolism, in vivo and in vitro

• Chia oil recovered glycolysis enzymes, glucose tolerance and AKT phosphorylation. • Chia oil and flour decreased adiposity and increased AMPK gene expression. • Chia hydrolyzed phenolics did not improve AKT phosphorylation of protein in HepG2 cells. • Chia hydrolyzed phenolics decreased glycolytic and gluconeogenic enzymes in vitro. The influence of chia ( Salvia hispanica L.) flour and oil on glucose metabolism (GM) in insulin resistant (IR) Wistar rats and the effect of chia hydrolyzed phenolics extract (CHPE) on GM in IR HepG2 cells were evaluated. In vivo study: animals were divided into four groups: AIN-93M, high-fat and high-fructose (HFHF), HFHF with chia flour (14.7%) or chia oil (4%). In vitro study: IR HepG2 cells were treated with CHPE (80 ppm). In vivo , chia flour and oil reduced adiposity and increased AMPK mRNA. Chia oil improved glucose tolerance, increased AKT1[pS473] protein level, mRNA of insulin receptor, FOXO1 and glycolysis enzymes. In vitro , CHPE decreased gluconeogenesis enzymes mRNA. Chia flour and oil decreased adiposity, but only chia oil was able to improve glucose tolerance and restore energy fuel system in liver of rats fed HFHF diet. CHPE decreased mRNA levels of gluconeogenesis enzymes.

Sea-Buckthorn Flavonoids Alleviate High-Fat and High-Fructose Diet-Induced Cognitive Impairment by Inhibiting Insulin Resistance and Neuroinflammation.

Sea-buckthorn flavonoids (SFs) have been used as functional food components for their bioactive potential in preventing metabolic complications caused by diet, such as obesity and inflammation. However, the protective effect of SFs on cognitive functions is not fully clear. In this study, a high-fat and high-fructose diet (HFFD)-induced obese mice model was treated with SFs for 14 weeks. It was found that the oral SF administration (0.06% and 0.31% w/w, mixed in diet) significantly reduced bodyweight gain and insulin resistance in the HFFD-fed mice. SFs significantly prevented HFFD-induced neuronal loss and memory impairment in behavioral tests. Additionally, SFs also suppressed the HFFD-induced synaptic dysfunction and neuronal damages by increasing the protein expressions of PSD-95. Furthermore, SF treatment activated the ERK/CREB/BDNF and IRS-1/AKT pathways and inactivated the NF-κB signaling and its downstream inflammatory mediator expressions. In conclusion, SFs are a potential nutraceutical to prevent high-energy density diet-induced cognitive impairments, which could be possibly explained by their mediating effects on insulin signaling and inflammatory responses in the brain.

MetAP2 inhibitor treatment of high-fat and -fructose-fed dogs: impact on the response to oral glucose ingestion and a hyperinsulinemic hyperglycemic clamp.

We examined the methionine aminopeptidase 2 inhibitor fumagillin in dogs consuming a high-fat and -fructose diet (HFFD). In pilot studies (3 dogs that had consumed HFFD for 3 yr), 8 wk of daily treatment with fumagillin reduced food intake 29%, weight 6%, and the glycemic excursion during an oral glucose tolerance test (OGTT) 44%. A second group of dogs consumed the HFFD for 17 wk: pretreatment (weeks 0-4), treatment with fumagillin (FUM; n = 6), or no drug (Control, n = 8) (weeks 4-12), washout period (weeks 12-16), and fumagillin or no drug for 1 wk (week 17). OGTTs were performed at 0, 4, 11, and 16 wk. A hyperinsulinemic hyperglycemic clamp was performed in week 12; 4 chow-fed dogs underwent identical clamps. Kilocalories per day intake during the treatment period was 2,067 ± 50 (Control) versus 1,824 ± 202 (FUM). Body weights (kg) increased 1.9 ± 0.3 vs. 2.7 ± 0.8 (0-4 wk) and 1.2 ± 0.2 vs. -0.02 ± 0.9 (4-12 wk) in Control versus fumagillin. The OGTT glycemic response was 30% greater in Control versus fumagillin at 11 wk. Net hepatic glucose uptake (NHGU; mg·kg-1·min-1) in the Chow, Control, and fumagillin dogs was ~1.5 ± 0.6, -0.1 ± 0.1, and 0.3 ± 0.4 (with no portal glucose infusion) and 3.1 ± 0.6, 0.5 ± 0.3, and 1.5 ± 0.5 (portal glucose infusion at 4 mg·kg-1·min-1), respectively. Fumagillin improved glucose tolerance and NHGU in HFFD dogs, suggesting methionine aminopeptidase 2 (MetAP2) inhibitors have the potential for improving glycemic control in prediabetes and diabetes.

Effects of protocatechuic acid on ameliorating lipid profiles and cardio-protection against coronary artery disease in high fat and fructose diet fed in rats.

A coronary heart disease leads to increase in obesity and metabolic dysfunction. Protocatechuic acid (PCA), due to its antioxidant, anti-inflammatory, neuro protective activities was found efficient as cardio-protective in coronary heart disease. Our study investigated hypolipidemic and cardioprotective effects of protocatechuic acid in the coronary artery disease induced by high fat and fructose diet (HFD) rat models. A diet rich in fat and fructose was fed to male Wistar rats prior to the start of experimental procedures. Serum lipid levels and hepatic triglycerides (TG) and total cholesterol (TC) levels were examined and analyzed. Both in vitro an in vivo pancreatic lipase activity was determined as well. Histopathological examination was performed and their results were noted. Noteworthy reduction of serum lipid levels and hepatic TG and TC levels was seen in groups treated with simvastatin (SIM; 20 mg/kg) and PCA (50 and 100 mg/kg) in comparison to HFD groups. Pancreatic lipase activity was reduced in the SIM group and the group treated with doses of PCA (50 and 100 mg/kg). A marked increase in gain in body weight per week (P<0.05) was achieved in HFD group. Coronary risk index (CRI) and Atherogenic index of plasma (AIP) showed decreased index values after treatments with SIM and PCA (50 and 100 mg/kg), respectively. Our findings confirmed the efficacious cardio-protective and hypolipidaemic activities of protocatechuic acid in coronary artery disease induced in rats with fat and fructose rich diet.

Combination of Scutellaria baicalensis and Metformin Ameliorates Diet-Induced Metabolic Dysregulation in Mice via the Gut-Liver-Brain Axis.

Scutellaria baicalensis (SB), a herbal medicine, is commonly used to treat metabolic diseases, while Metformin (MF) is a widely used drug for type 2 diabetes. The purpose of this study was to investigate whether co-treatment of SB with MF could produce a potential therapeutic effect on high-fat and high-fructose diet (HFFD)-induced metabolic dysregulation. First, we optimized the dose of SB (100, 200, 400, and 800[Formula: see text]mg/kg) with MF (200[Formula: see text]mg/kg) in HFFD-induced C57BL6J mice. Next, the optimized dose of SB (400[Formula: see text]mg/kg) was co-administered with MF (50, 100, and 200[Formula: see text]mg/kg) in a similar animal model to find the effective combinations of SB and MF. Metabolic markers were determined in serum and tissues using different assays, histology, gene expression, and gut microbial population. The SB and MF co-treatment significantly decreased the body, liver, and VAT weights. The outcome of OGTT was improved, and the fasting insulin, HbA1c, TG, TC, LDL-c, AST, and ALT were decreased, while HDL-c was significantly increased. Histological analyses revealed maintained the integrity of liver, adipose tissue, and intestine prevented lipid accumulation in the liver and intestine and combated neuronal damage in the brain. Importantly, controlled the expression of PPAR[Formula: see text], and IL-6 genes in the liver, and expression of BDNF, Glut1, Glut3, and Glut4 genes in the brain. Treatment-specific gut microbial segregation was observed in the PCA chart. Our findings indicate that SB and MF co-treatment is an effective therapeutic approach for HFFD-induced metabolic dysregulation which is operated through the gut-liver-brain axis.

Secoisolariciresinol diglucoside alleviates hepatic lipid metabolic misalignment involving the endoplasmic reticulum-mitochondrial axis.

Secoisolariciresinol diglucoside (SDG) has positive effects on obesity and its complications. We investigated the effects and mechanism of SDG on high-fat and high-fructose diet (HFFD)-induced hepatic lipid metabolic disorders. Supplementation with 40 mg kg-1 d-1 SDG for 12 weeks significantly reduced the body weight and the ratio of liver and adipose tissue to body weight in HFFD-fed mice. Serum and hepatic TG, TC, HDL-C, and LDL-C levels became normalized, and hepatic lipid metabolic disorders lessened because of the downregulation of lipid synthesis genes and upregulation of lipid oxidation genes. SDG also alleviated endoplasmic reticulum (ER) stress and mitochondrial dysfunction by regulating the ER stress factors Bip, IRE1α, Xbp1, Atf6, Perk, and Chop and mitochondrial function-related genes Cox5b, Cox7a1, Cox8b, and Cycs. Results with HepG2 cells confirmed that SDG regulated lipid metabolic disorders by the ER stress-Ca2+-mitochondrial-associated pathway. Our study provides a strategy for the treatment of obesity and its related comorbidities.

Soursop (Annona Muricata) Leaf Water Extract (SLWE) Prevent Pancreatic Β-Cell Damage in Male Wistar Rats Induced By High Fat and High Fructose (HFHF) Diet

Background: A high-fructose high fat (HFHF) diet induces dyslipidemia, which can interfere with pancreatic function. Soursop leaf (Annona muricata) water extract (SLWE) has ant hyperlipidemia and antioxidants activity. This research aims to assess the activity of SLWE in preventing pancreatic β-cell damage in male Wistar rats induced by the HFHF diet. Method: This study is a post test group control only research design. Twenty-five wistar rats aged 10-12 weeks, weighing 175- 200 g, were randomly divided into five study groups, namely the normal group (N) laboratory standard diet, the positive group (P) HFHF diet, and the treatment group 1 (T1) HFHF diet+SLWE dose 100mg/kgbw, treatment group 2 (T2) HFHF diet+SLWE dose 200mg/kgbw, and treatment group 3 (T3) HFHF diet+SLWE dose 400mg/kgbw. Diet is given for ten weeks. Measurement of fasting blood glucose levels were taken from the tail using a rapid test conducted at the beginning and end of the study. At the end of the study, the rates were sacrificed under anesthesia. The rats pancreatic organs were surgically removed and blood was taken from the ventricular puncture. Pancreatic organs are used to measure the percentage of pancreatic β cells, which expressed FoxO1 protein, by flow cytometry method, and the average area of pancreatic β cells by immunohistochemistry. Blood is centrifuged to obtain blood plasma, which is used to measure insulin levels. Data were analyzed using One Way Anova and Kruskal Wallis with a significance of p &lt;0.05. Result: SLWE did not cause changes in blood glucose levels, but the administration of SLWE at a doses of 200mg/kgBB tended to increase insulin levels (p&gt; 0.05), decreased percentage number of β-cells expressing FoxO1, and decreased the average area of pancreatic β cells compared to P group (p &lt;0.05). Conclusion: SLWE can prevent pancreatic β-cell damage by increase insulin secretion without causing pancreatic β-cell proliferation.

Opisthorchis viverrini Infection Augments the Severity of Nonalcoholic Fatty Liver Disease in High-Fat/High-Fructose Diet-Fed Hamsters.

The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide, including in regions where helminth infections such as the fish-borne liver fluke Opisthorchis viverrini (Ov) also occur. We investigated the effects of a high-fat and high-fructose (HFF) diet on the development and progression of NAFLD in experimental opisthorchiasis. Two groups of hamsters were infected with Ov for 4 months before the experiment to induce chronic inflammation. One of these groups (OvHFF) was fed with a HFF diet for up to further 4 months. One uninfected group of hamsters served as the normal control group, and another received the HFF diet (HFF group) for up to 4 months. Histopathology, biochemical parameters, and ultrastructural features of liver were investigated. In a short-term treatment, the OvHFF group showed significantly better homeostatic model assessment for insulin resistance level and lower liver lipid than did the HFF group. By contrast, histopathological characteristics of severe NAFLD were prominent in the OvHFF group after 4 months on the HFF diet, findings which were supported by confirmatory ultrastructural changes. In conclusion, opisthorchiasis induced the severe NAFLD in hamsters fed high-fat/high-fructose diets.

Anti-obesity effect of Lactobacillus rhamnosus LS-8 and Lactobacillus crustorum MN047 on high-fat and high-fructose diet mice base on inflammatory response alleviation and gut microbiota regulation.

The objective of the study was to evaluate the anti-obesity effect of Lactobacillus rhamnosus LS-8 and Lactobacillus crustorum MN047, and illustrate the potential functional mechanism about the alleviation of high fat and high fructose diet (HFFD) induced obesity and related metabolic abnormalities. C57BL/6J mice were subjected to a standard or HFFD with or without supplementation of L. rhamnosus LS-8 and L. crustorum MN047 for 10weeks. Obesity related metabolic indices including glucose tolerance, insulin resistance, serum lipid, liver function, hormones and inflammatory cytokines were assessed by standard protocols. For the monitoring of inflammatory response and lipid metabolism, transcriptional levels were profiled in liver and/or adipose tissues. Furthermore, gut microbiota composition analyses in the fecal samples were performed using 16S rRNA gene sequencing, and gut microbial metabolites,including lipopolysaccharide (LPS) and short-chain fatty acids (SCFAs), were also tested for the assessment of the relationship between gut microbiota variation and inflammatory response. Administration with L. rhamnosus LS-8 and L. crustorum MN047 significantly mitigated body weight gain and insulin resistance, and inflammatory response (TNF-α, IL-1β and IL-6 levels in serum and corresponding mRNA levels in adipose tissues) was significantly inhibited in these two strains-treated mice. Moreover, L. rhamnosus LS-8 and L. crustorum MN047 could partially normalized mRNA expression levels involved in lipid metabolism including Pparγ, Srebp-1c, CD36, Fabp2 and FAS. In addition, these two strains manipulated gut microbiota by decreasing the abundance of Bacteroides and Desulfovibrio and increasing that of Lactobacillus and Bifidobacterium, which in turn raised the levels of feces SCFAs and lowered the levels of circulating LPS. These results indicated that L. rhamnosus LS-8 and L. crustorum MN047 supplementation possessed the anti-obesity effect on the HFFD fed mice by alleviating inflammatory response and regulating gut microbiota, which further suggested that these two probiotics can be considered as an alternative dietary supplement in combination with the preventive and therapeutic strategies against obesity and related complications.