High-fat Diet Rats Research Articles

A network pharmacology-based approach to explore the effect of dihydromyricetin on non-alcoholic fatty liver rats via regulating PPARG and CASP3

BackgroundNon-alcohol fatty liver disease (NAFLD) is the most prevalent hepatopathy in China, with few effective cures currently. This work aimed to confirm the effect of DHM in vivo/vitro and explore the potential mechanism based on a network pharmacology-based approach. MethodsThe rats were fed using a high-fat diet (HFD) to accumulate lipid. DHM at different concentrations was used to treat the HFD rats. The serum total cholesterol (TC), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were detected using ELISA kits. The target genes of DHM against NAFLD were screened by online databases. Then, the cytotoxicity of DHM in primary hepatocytes and HepG2 cells was determined by MTT reagent. qRT-PCR was used to quantify the expression level of PPAGR and CASP3 mRNA. Cell apoptosis and intracellular triglyceride (TG) were detected. ResultsHFD diet increased rat liver weight/body weight ratio, serum TC, ALT, and AST. But DHM treatment can reduce these elevated indicators. DHM targeted 14 potential genes in NAFLD. PPARG and CASP3 were two hub genes for DHM against NAFLD, with score factor coefficients of −7.1 and −6.8 kcal/mol. DHM reduced the increased PPARG mRNA level and intracellular TG induced by palmitic acid. DHM can reduce the increased CASP3 mRNA level and cell apoptosis induced by palmitic acid. ConclusionThis work demonstrates a mechanism of DHM that alleviates lipid metabolism disorder and cell apoptosis for the treatment of NAFLD, evidencing the potential application of DHM in NAFLD.

Zingerone attenuates intestinal injury and colitis caused by a high-fat diet through Nrf2 signaling regulation

This study examined the protective effect of Zingerone against a high-fat diet (HFD)-induced intestinal damage. Control and HFD rats were treated with the vehicle or Zingerone (100 mg/kg, orally) (n = 8 rats/groups). An extra group, HFD + Zingerone + brusatol (an Nrf2 inhibitor). This study treatment lasted four weeks. Zingerone reduced the nuclear levels of NF-B p65 in control and HFD-fed rats while increasing SOD, CAT, GSH, levels of mRNA, cytoplasmic levels, and Nrf2 nuclear levels. Zingerone treatment attenuated the duodenal epithelial damage and maintained the mucosal barrier by reducing plasma FITC-DX and serum LPS in rats fed with HFD. Concomitantly, it lowered the duodenal MDA, TNF-α, IL-6, and IL-1β levels. These impacts included changes in body weight, duodenal lipid levels, and Keap-1 expression, a natural Nrf2 inhibitor. We concluded that Zingerone reduces HFD-induced duodenal injury. These findings support Zingerone's clinical applicability against various inflammatory diseases of the intestine.

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

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

Duodenal mucosal resurfacing with photodynamic therapy using methylene blue in a mouse model

BackgroundThe duodenum has emerged as a key player in metabolic diseases. The objective was to evaluate the safety and efficacy of intra-duodenal PDT using methylene blue in managing glycemic control and weight reduction. MethodsOptimal concentration of methylene blue and conditions for intra-duodenal PDT were determined through in vitro experiments. After injecting methylene blue into the duodenum, we performed intra-duodenal PDT. High-fat diet rats were used to assess the efficacy of intra-duodenal PDT through measures of oral glucose tolerance, insulin sensitivity, and weight change. Immunohistochemical staining was also conducted to examine GLP-1 and GIP-producing cells in the ileum and duodenum, respectively. ResultsIntroduodenal PDT reduced villous height of duodenum at 48 h, which was fully recovered at 30 days without complications. Rats treated with PDT showed significantly lower blood glucose levels with glucose loading and improved insulin sensitivity than rats in the sham-treatment group. The PDT group also had a significant reduction in body weight compared to the sham-treatment group at 30 days after intervention, although food intake was not significantly different between the two groups. Numbers of GLP-1 and GIP producing cells in the ileum and irradiated area were significantly higher in the PDT group than in the sham-treatment group. ConclusionsIntra-duodenal PDT using methylene blue showed a feasible therapeutic modality in improving metabolic parameters. However, large animal experiments and mechanism studies are needed to determine the clinical relevance. The possibility of repeating this treatment every 30 days and its accompanying complications should be further studied.

Weizmannia coagulans JA845 improves atherosclerosis induced by vitamin D3 and high-fat diet in rats through modulating lipid metabolism, oxidative stress, and endothelial vascular injury.

Probiotics have been proved to be strongly linked to the occurrence and progression of atherosclerosis. This study aimed to investigate the improved effects and mechanisms underlying a potential probiotic, Weizmannia coagulans JA845, on atherosclerosis. Male Sprague-Dawley rats supported on a high-fat diet with vitamin D3 supplementation were subjected to W. coagulans JA845 treatment. W. coagulans JA845 obviously alleviated histological abnormalities of the abdominal aorta. After 6 weeks of W. coagulans JA845 administration, levels of TG, TC, LDL, ox-LDL, ROS, and MDA in the JA845 group decreased significantly, and those of HDL, GSH-Px, and SOD were markedly elevated. Treatment with W. coagulans JA845 also inhibited the secretion of ICAM-1 and VCAM-1 and regulated the plasma NO and eNOS content. In brief, administration of W. coagulans JA845 promoted the expression of the SIRT3/SOD2/FOXO3A pathway, inhibited the lipid metabolism pathway, SREBP-1c/FAS/DGAT2, and suppressed the JNK2/P38 MAPK/VEGF pathway implicated in endothelial injury. These results indicated W. coagulans JA845 improved atherosclerosis by regulating lipid metabolism, antioxidative stress, and protecting against endothelial injury.

Extension Region Domain of Soybean 7S Globulin Contributes to Serum Triglyceride-Lowering Effect via Modulation of Bile Acids Homeostasis.

Soybean 7S globulin (β-conglycinin), a major soybean storage protein, has been demonstrated to exert remarkable triglyceride (TG) and cholesterol-lowering effects, yet the underlying mechanism remains controversial. A comparative investigation is performed to assess the contribution of different structural domains of soybean 7S globulin, including core region (CR) and extension region (ER) domains, to biological effects of soybean 7S globulin using a high-fat diet rat model. The results show that ER domain mainly contributes to the serum TG-lowering effect of soybean 7S globulin, but not for CR domain. Metabolomics analysis reveals that oral administration of ER peptides obviously influences the metabolic profiling of serum bile acids (BAs), as well as significantly increased the fecal excretion of total BAs. Meanwhile, ER peptides supplementation reshapes the composition of gut microbiota and impacts the gut microbiota-dependent biotransformation of BAs which indicate by a significantly increased secondary BAs concentration in fecal samples. These results highlight that TG-lowering effects of ER peptides mainly stem from their modulation of BAs homeostasis. Oral administration of ER peptides can effectively lower serum TG level by regulating BAs metabolism. ER peptides have potential to be used as a candidate pharmaceutical for the intervention of dyslipidemia.

Saudi date cultivars' seed extracts inhibit developing hepatic steatosis in rats fed a high-fat diet

This research aim was to assess the impact of the seed extracts of the date cultivars (Qatara, Barhi, and Ruthana) on rat’s liver steatosis, oxidative stress, and inflammation triggered by feeding a high-fat diet (HFD). The experimental design was based on random partitioning into two groups; one that received the standard diet and another that received the HFD diet. The HFD rats were orally administered Lipitor or date seed extracts at 300 or 600 mg/kg/day for 4 weeks. Accordingly, feeding rats HFD significantly increased body and liver weights, hepatic and serum lipid levels, glucose, insulin, HOMA-IR, liver function enzymes, and inflammation markers, and decreased oxidative stress enzymes. Oral administration of Barhi and Ruthana date seed extracts significantly decreased body and liver weights. Serum and liver total cholesterol TC, Triglycerides TGs, and free fatty acids FFAs were also decreased as were AST, ALT, MAD, leptin, and CRP, with a concomitant increase in SOD, GSH, and CAT. Furthermore, similar to Lipitor, oral administration of the extracts reduced inflammation markers such as TNF-α, serum CRP, IL-6, IL-1β, and leptin while increasing IL-10 and adiponectin levels. Histological observation revealed that extract administration improved hepatocyte and parenchymal structures and decreased lipid deposition. In conclusion, both Barhi and Ruthana seed extracts showed strong hepatoprotective, anti-inflammatory, and antioxidant effects against HFD-induced liver steatosis. And date seeds have other beneficial potential for prevention and treatment of various diseases, which can be studied in the future.

Qinlian hongqu decoction ameliorates hyperlipidemia via the IRE1-α/IKKB-β/NF-κb signaling pathway: Network pharmacology and experimental validation

Ethnopharmacological relevanceQinlian Hongqu decoction (QLHQD) is a traditional Chinese medicine (TCM) formula. It has previously been found to mitigate hyperlipidemia, although its mechanism requires further clarification. Aim of the studyThis study explored QLHQD's mechanism in treating hyperlipidemia based on network pharmacology and experimental validation. Materials and methodsThe components of QLHQD were analyzed by means of ultrahigh performanceliquid chromatography-quadrupole/orbitrapmass spectrometry (UHPLC-Q-Orbitrap-HRMS) and the targets of hyperlipidemia were predicted using the Swiss ADME, GeneCards, OMIM, DrugBank, TTD, and PharmGKB databases. A drug-component-target-disease network was constructed using Cytoscape v3.7.1. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses were performed using the Bioinformatics platform. Based on the KEGG results, the non-alcoholic fatty liver disease signaling pathways were selected for experimental validation in an animal model. ResultsWe identified 34 components of QLHQD, 94 targets of hyperlipidemia, and 18 lipid metabolism-related pathways from the KEGG analysis. The results of the animal experiment revealed that QLHQD alleviated lipid metabolism disorders, obesity, insulin resistance, and inflammation in rats with hyperlipidemia induced by high-fat diets. Additionally, it reduced the expression of IRE1-α, TRAF2, IKKB-β, and NF-κB proteins in the liver of hyperlipidemic rats. ConclusionQLHQD is able to significantly mitigate hyperlipidemia induced via high-fat diets in rats. The mechanism of action in this regard might involve regulating the IRE1-α/IKKB-β/NF-κB signaling pathway in the liver, thereby attenuating inflammatory responses and insulin resistance.

The Protective Effects of Melatonin against Brain Disorders Induced by the Western Diet in Male Rats

Globally, the effects of consuming a diet rich in fat have gained great concerted attention. The current study was conducted to evaluate the protective effects of melatonin on neurological disorders induced by the western diet in rats. A total of 30 adult male white local Iraqi rats were randomly assigned to three equal groups, including control (CC), high-fat diet (HFD), and melatonin group (HFD+M, a high-fat diet along with intraperitoneal injections of 10 mg/kg body weight melatonin) for 8 weeks. The rats were analyzed in terms of brain tissue concentration of dopamine, tumor necrosis factor (TNF), and nervous system impairment using Barns maze task and elevated plus maze. The findings revealed a significant decline in the dopamine concentration of the HFD group after 8 weeks of treatment, compared to CC and HFD+M groups. Moreover, there was a significant increase in brain TNF-α concentration in the group fed HFD, compared with CC and HFD+M. Finally, the melatonin treatment significantly reduced spatial memory impairments and anxiety induced by HFD in rats. After 8 weeks, the histological examination revealed that brain section rats on an HFD indicated significant congestion in the blood vessels with marked cerebral edema, where there was a dilation of Virchow-Robin space, severe congestion, and infiltration of inflammatory cells in the meninges. The HFD+M groups showed normal meninges without any inflammatory exudate except for a few congestions in the blood vessels and no or mild vacuolations in the cerebral tissue, gliosis, and astrocytosis. In contrast, male rats fed an HFD showed vacuolation and aerophagia in brain tissue and a marked aggregation of the proliferation of astrocytes and a proliferation of microglial cells in the cerebral. In conclusion, HFD impairs brain neurotransmitters, induces pro-inflammatory changes, and affects learning ability and memory by changing the structure of neural tissue. Melatonin can ameliorate HFD-caused effects.

The Effect of Lipopolysaccharide-Stimulated Adipose-Derived Mesenchymal Stem Cells on NAFLD Treatment in High-Fat Diet-Fed Rats.

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are 2 common liver diseases that currently lack effective treatment options. This study aimed to investigate the effect of lipopolysaccharide (LPS)-stimulated adipose-derived stem cells (ADSCs) on NAFLD treatment in an animal model. Male Wistar rats were fed a high-fat diet (HFD) to induce NAFLD for 7 weeks. The rats were then categorized into 3 groups: Mesenchymal stem cell (MSC), MSC + LPS, and fenofibrate (FENO) groups. Liver and body weight were measured, and the expression of genes involved in fatty acid biosynthesis, β-oxidation, and inflammatory responses was assessed. Lipopolysaccharide-stimulated ADSCs were more effective in regulating liver and body weight gain and reducing liver triglyceride (TG) levels compared to the other groups. Treatment with LPS-stimulated ADSCs effectively corrected liver enzymes, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and lipid factors, including low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) values, better than treatment with both FENO and MSCs. ADSCs + LPS treatment significantly decreased transforming growth factor β (TGF-β) and genes associated with inflammatory responses. Additionally, there was a significant reduction in reactive oxygen species (ROS) levels in the rats treated with ADSCs + LPS. Lipopolysaccharide-stimulated ADSCs showed potential in alleviating NAFLD by reducing inflammatory genes and ROS levels in HFD rats, demonstrating better results than treatment with ADSCs and FENO groups alone.

245-LB: Glucagon Infusion into the Mediobasal Hypothalamus Lowers Hepatic Triglyceride Secretion

Diabetes and obesity are associated with dysregulated liver lipid metabolism. Glucagon has an essential role in lipid metabolism, in addition to regulating glucose homeostasis. The brain is a key coordinator of whole-body metabolism. Glucagon signalling in the mediobasal hypothalamus (MBH), a forebrain region that senses hormones and nutrients to regulate metabolism, lowers hepatic glucose production and appetite. However, whether glucagon action in the MBH affects lipid homeostasis in healthy and high-fat diet (HFD)-fed animals remains unknown. We assessed glucagon signaling in the MBH in regulating hepatic TG secretion in chow-fed normolipidemic and HFD-induced hyperlipidemic rats. Stereotaxic MBH cannulation and vascular catheterizations in Sprague-Dawley rats allowed for direct MBH infusions, intravenous (IV) injections, and blood sampling. Plasma TGs were measured in 10h-fasted rats after IV poloxamer injection with concurrent MBH infusions. MBH glucagon decreased TG secretion compared to MBH vehicle control animals. This hypothalamic effect of glucagon was blocked by a simultaneous MBH co-infusion of an antagonist to the glucagon receptor (GCGR) and by protein kinase A (PKA) inhibition in the MBH in chow-fed rats. Direct MBH infusion of a PKA activator recapitulated the TG-lowering effects of MBH glucagon. Together, this suggests that MBH glucagon signals via a MBH GCGR-PKA pathway. Interestingly, both MBH glucagon and MBH PKA activation lowered TG secretion and plasma FFAs in HFD-induced hyperlipidemic animals. However, MBH glucagon did not affect hepatic TG content or liver lipogenic protein levels of MTP, FAS, or pACC:ACC of RC and HFD rats compared to their MBH vehicle controls. We demonstrate that hypothalamic glucagon modulates hepatic TG secretion via a MBH GCGR-PKA signalling pathway, and activating MBH glucagon signalling improves lipid metabolism in hyperlipidemic rats. These findings may provide therapeutic insight on lowering lipids in hyperlipidemia. Disclosure M. S. Grewal: None. B. Vasilev: None. C. M. Soltys: None. B. Lum: None. J. T. Yue: None. Funding Canadian Institutes of Health Research (PJT-378765); Canada Foundation for Innovation (37267); Canada Research Chairs Tier 2 in Brain Regulation of Metabolism

Ameliorative effects of phlorotannin-rich fraction of Sargassum tenerrimum in high-fat diet and low dose streptozotocin-induced metabolic changes and oxidative stress in diabetic rats

Introduction: Type 2 diabetes mellitus (T2D) is a progressing polygenic disease demanding a multitargeted treatment strategy. Sargassum tenerrimum (ST) is a marine brown alga with potentially bioactive chemicals that could be used as innovative biotherapeutics for diabetes treatment. The current research examined the potential of the phlorotannin-rich fraction from S. tenerrimum (PST) to mitigate diabetes in Wistar albino rats induced with high-fat diet (HFD) and streptozotocin (STZ) administration. Methods: Diabetic rats were given PST (200 and 400 mg/kg) or metformin (250 mg/kg) orally three weeks, and followed by the measurements of insulin, glycemic factors, biological markers of oxidative stress, tumor necrosis factor-alpha (TNF-α), as well as hepatic and pancreatic histopathological changes. Results: PST treatment significantly decreased fasting blood glucose, insulin resistance, lipid profile, hepatic profile, and TNF- α levels and improved serum insulin and glucose tolerance in diabetic rats. In the skeletal muscles of diabetic rats, PST led to a significant rise in antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) reductase, and a decrease in lipid peroxidation. Furthermore, PST treatment significantly reduced pancreatic-cell damage and hepatic fatty accumulation. PST was more efficacious at 400 mg/kg exhibiting a dose-dependent effect. Conclusion: PST improves glucolipid metabolism in HFD and STZ-induced diabetic rats, probably by reducing hyperglycemia, insulin resistance, dyslipidemia, oxidative stress, inflammation, and damage to pancreatic and hepatic architectures. The findings suggest that PST has a curative impact on diabetes mellitus type 2 and represents a new subject of study for the treatment of diabetes naturally.

RYGB surgery has modest effects on intestinal morphology and gut hormone populations in the bypassed biliopancreatic limb but causes reciprocal changes in GLP-2 and PYY in the alimentary limb.

Roux-en-Y gastric-bypass (RYGB) induced alterations in intestinal morphology and gut-cell hormone expression profile in the bypassed biliopancreatic-limb (BPL) versus the alimentary-limbs (AL) are poorly characterised. This pilot study has therefore explored effects following RYGB in high-fat-diet (HFD) and normal-diet (ND) rats. Female Wistar rats (4-week-old) were fed HFD or ND for 23-weeks prior to RYGB or sham surgeries. Immunohistochemical analysis of excised tissue was conducted three-weeks post-surgery. After RYGB, intestinal morphology of the BPL in both HFD and ND groups was unchanged with exception of a small decrease in villi width in the ND-RYGB and crypt depth in the HFD-RYGB group. However, in the AL, villi width was decreased in ND-RYGB rats but increased in the HFD-RYGB group. In addition, crypt depth decreased after RYGB in the AL of HFD rats. GIP positive cells in either limb of both groups of rats were unchanged by RYGB. Similarly, there was little change in GLP-1 positive cells, apart from a small decrease of numbers in the villi of the BPL in HFD rats. RYGB increased GLP-2 cell numbers in the AL of ND-RYGB rats, including in both crypts and villi. This was associated with decreased numbers of cells expressing PYY in the AL of ND-RYGB rats. The BPL appears to maintain normal morphology and unchanged enteroendocrine cell populations despite being bypassed in RYGB-surgery. In contrast, in the AL, villi area is generally enhanced post-RYGB in ND rats with increased numbers of GLP-2 positive cells and decreased expression of PYY.

Taurine alleviated hepatic steatosis in oleic acid-treated-HepG2 cells and rats fed a high-fat diet

Taurine has been proven in many trials to alleviate the symptoms of metabolic associated fatty liver disease. Here its protective effect for hepatic steatosis and modulation of AMP-activated protein kinase and insulin signaling pathway were investigated. Steatotic HepG2 cell established with oleic acid (0.05 mmol/L), treated with taurine (5 mmol/L), dorsomorphin (10 μmol/L) for 24 h. Sprague Dawley rats were divided into regular and high-fat diet (HFD) groups, and their corresponding taurine (70 or 350 mg/kg BW/d) groups, fed for 8 weeks. In steatotic cell, taurine reduced the TG concentration and SREBP-1c, PPARγ, FAS, ACC, SCD1 protein levels, decreased phosphorylation of mTOR, IRS1 (Ser302), increased phosphorylation of AMPKα, LKB1, PI3K, Akt, ACC. While dorsomorphin eliminated taurine's TG-lowering effect. In HFD-fed rats, taurine reduced liver TG, serum TG, ALT, AST, IL-1β, IL-4, TNF-α. The effects of taurine on the main factors of fatty acid synthesis were mostly consistent with cell experiments, and the reduction of microRNAs (451, 33, 291b) was aligned with the improvement in LKB1 and AMPK expression in HFD rats. Taurine alleviated steatosis-induced inhibition of IRS1-PI3K-Akt pathway, but suppressed its positively regulated downstream factor mTOR. In parallel, taurine reduced steatosis by activating LKB1-AMPKα pathway via phosphorylation and no-phosphorylation manner, then inhibiting SREBP-1c directly or by suppressing mTOR phosphorylation.

The restorative effects of graded intensities of exercise training on the biochemical and nutritional status of obese induced male Wistar rats (Rattus novegicus)

The purpose of this study was to evaluate the specific effects of 12 weeks of intensive, graded intensities of exercise training on nutritional parameters and some plasma biochemical parameters in high-fat diet and sucrose obesity-induced (HFDS) Wistar rats. In evaluating the restorative effects of graded exercise training as an intervention in managing obesity, 25 male Wistar rats who were 7 weeks old were used. These 25 rats were broadly grouped into 5 rats as controls and 20 rats as experiments. In the first phase of the experiment, which involved the induction of obesity, the rats were fed on HFDS containing 35% total fat, 39% carbohydrates, 23% protein, 6% fiber per 100 grams, and 60% sucrose solution per 100 mL for 12 weeks, while the 5 rats in the control group were fed on a normal rodent diet containing 5% total fat, 39% carbohydrates, 23% protein, and 6% fiber per 100 grams. In the second phase, which was the interventional phase, the 20 HFDS-induced obese rats were randomly assigned into 4 groups: the control (sedentary group), low, medium, and high-intensity exercise training groups, and were subjected to various intensities of exercise training. All experimental groups received the HFDS throughout the exercise training period. After 84 days of exercise training intervention, the final body weight, plasma biochemical parameters including total cholesterol (TC), triglyceride (TG), and high-density lipoprotein cholesterol (HDLC) concentrations, and nutrition parameters including feed efficiency (FE), feed consumption (FC), and caloric intake (CI) were assessed. The study established that graded exercise training has a direct, inversely proportional reduction in TC, TG, and LDLC concentrations. In conclusion, medium- to high-intensity exercise training is associated with restoring the dyslipidemic profile in the serum of rats and also increased feed efficiency.

Mitigation effect of galangin against aortic dysfunction and hypertrophy in rats with metabolic syndrome

Vascular alterations induced by a high-fat diet (HFD) are involved in the development of hypertension. Galangin, a flavonoid, is the major active compound isolated from galangal and propolis. The objective of this study was to investigate the effect of galangin on aortic endothelial dysfunction and hypertrophy, and the mechanisms involved in HFD-induced metabolic syndrome (MS) in rats. Male Sprague-Dawley rats (220–240 g) were separated into three groups: control + vehicle, MS + vehicle, and MS + galangin (50 mg/kg). Rats with MS received HFD plus 15% fructose solution for 16 weeks. Galangin or vehicle was orally administered daily for the final four weeks. Galangin reduced body weight and mean arterial pressure in HFD rats (p < 0.05). It also reduced circulating fasting blood glucose, insulin, and total cholesterol levels (p < 0.05). Impaired vascular responses to the exogenous acetylcholine observed in the aortic ring of HFD rats were restored by galangin (p < 0.05). However, the response to sodium nitroprusside did not differ between the groups. Galangin enhanced the expression of the aortic endothelial nitric oxide synthase (eNOS) protein and increased circulating nitric oxide (NO) levels in the MS group (p < 0.05). Aortic hypertrophy in HFD rats was alleviated by galangin (p < 0.05). Increases in tumour necrosis factor-alpha (TNF-α), interleukin (IL)-6 levels, angiotensin-converting enzyme activity and angiotensin II (Ang II) concentrations in rats with MS were suppressed in galangin treated group (p < 0.05). Furthermore, galangin reduced the upregulation of angiotensin II type I receptor (AT1R) and transforming growth factor-beta (TGF-β) expression in rats with MS (p < 0.05). In conclusion, galangin alleviates metabolic disorders and improves aortic endothelial dysfunction and hypertrophy in the MS group. These effects were consistent with increased NO availability, reduced inflammation, and suppressing Ang II/AT1R/TGF-β signalling pathway.

Effect of β-Caryophyllene on oxidative stress, glucose metabolism in the skeletal muscle of high fat diet and fructose-induced type-2 diabetic adult male rats.

Skeletal muscle is where the majority of insulin-stimulated whole-body glucose elimination takes place under normal circumstances. A significant risk factor for metabolic diseases is high dietary fat consumption, which also increases stored fat mass. Natural solutions with anti-diabetic effectiveness and fewer side effects are becoming more popular as a result of the conventional pharmacological treatments' numerous negative side effects and high rates of secondary failure. Cannabis and a variety of culinary herbs and spices may include the naturally occurring sequiterpene β-caryophyllene. Among other things, it has antioxidant, anti-inflammatory, and anti-lipidemic properties. However, it is not yet known how β-caryophyllene affects the uptake and oxidation of glucose. Determining if β -caryophyllene has anti-diabetic properties in type-2 diabetes brought on by a high-fat diet was the objective of the current investigation. A sufficient dose of β-caryophyllene (200 mg/kg b.w.t., orally for 30 days) was given to type-2 diabetic rats fed a high-fat diet and given fructose as an inducer of diabetes to assess its anti-diabetic activity. The treatment of diabetes-induced rats with β -Caryophyllene restored the altered levels of blood glucose, serum insulin as well as the lipid parameters, oxidative stress markers, antioxidant enzymes. Our findings show that β-caryophyllene improves glycemia control by enhancing glucose absorption and oxidation in the skeletal muscle of type-2 diabetic rats. From the present findings, it is evident that β -caryophyllene can be used as an anti-diabetic drug.

Effect of lupeol on insulin resistance in adipose tissue by modulating the expression of insulin and inflammatory signaling molecules in high-fat diet and sucrose-fed diabetic rats

The prevalence of obesity and diabetes has increased globally as a result of lifestyle modifications including eating a high-fat diet and not exercising. The target tissues to insulin action are the key pathophysiological event contributing to the development of type 2 diabetes mellitus. The treatments for type 2 diabetes that are now accessible are ineffectual due to their unfavourable side effects. Hence, search drugs, from plant sources. Lupeol is widely present in various medicinal plants. It has been reported to elicit multitude of bioactivities including antilipidemic and antihyperglycemic activity. However, specific effect of Lupeol on insulin signaling molecules of adipose tissue remains unclear. Hence, the study aimed to assess the beneficial role of Lupeol on the expression of insulin‑signaling molecules in adipose tissue of high fat diet and sucrose-induced type‑2 diabetic rats. The oral effective dose of lupeol at a dose of 25 mg per kg body weight per day orally for 30 days is observed. Lupeol, being a powerful antioxidant agent, normalises hyperglycemia, dyslipidaemia, and hyperinsulinemia while also suppressing oxidative stress by scavenging high levels of ROS. It also enhances insulin signalling in type 2 diabetic rats in adipose tissues. Lupeol administration decreased the levels of pro-inflammatory cytokines, which may be due to lupeol's possible antioxidant and anti-inflammatory activities, and thus it promotes insulin sensitivity via altering pro-inflammatory signalling molecules in adipose tissue such as IL-6, TNF alpha, and NFkB. As a result of the current findings, it is concluded that lupoel possesses potent anti-diabetic characteristics and could be used as a phytomedicine for the treatment of type 2 diabetes.

High Fat Diet Suppresses Energy Expenditure Via Neurons in the Brainstem

Oxidation of fat by brown adipose tissue (BAT) contributes to energy balance and heat production. During cold exposure, BAT thermogenesis produces heat to warm the body. Obese subjects and rodents, however, show impaired BAT thermogenesis to the cold. Our previous studies suggest that vagal afferents synapsing in the nucleus tractus solitarius (NTS), tonically inhibit BAT thermogenesis to the cold in obese rats. NTS neurons send projections to the dorsal aspect of the lateral parabrachial nucleus (LPBd), which is a major integrative center that receives warm afferent inputs from the periphery and promotes inhibition of BAT thermogenesis. This study investigated the contribution of LPBd neurons in the impairment of BAT thermogenesis in rats fed a high-fat diet (HFD). By using a targeted dual viral vector approach, we found that chemogenetic activation of an NTS-LPB pathway inhibited BAT thermogenesis to the cold. We also found that the number of Fos-labelled neurons in the LPBd was higher in rats fed a HFD than in chow diet-fed rats after exposure to a cold ambient temperature. Nanoinjections of a GABAA receptor agonist into the LPBd area rescued BAT thermogenesis to the cold in HFD rats. These data reveal the LPBd as a critical brain area that tonically suppresses energy expenditure in obesity during skin cooling. These findings reveal novel effects of high-fat diets in the brain and in the control of metabolism and can contribute to the development of therapeutic approaches to regulate fat metabolism.

Therapeutic effects of Salvia balansae on metabolic disorders and testicular dysfunction mediated by a high-fat diet in Wistar rats

Medicinal plants offer an important therapeutic resource in treatment of male infertility. We aim to evaluate the possible therapeutic effects of Salvia balansae on metabolic disorders and testicular dysfunction resulting from a high-fat diet (HFD). Antioxidant activity of aqueous extract of S. balansae leaves was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, 2,2’-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assay and total antioxidant capacity (TAC) assay. Antidiabetic activity was determined by α-amylase inhibition. In vivo, HFD was administered in Wistar rats for 18 weeks and aqueous extract of S. balansae for the last 6 weeks (200 mg/Kg of body weight/day). At the term of experimentation, testosterone and some plasma parameters were analyzed and removed testes were subjected to a histomorphometric study. Our results show high levels of phenolic components in aqueous extract of S. balansae and significant antioxidant and antidiabetic activity. HFD increases body weight, causes type 2 diabetes, dyslipidemia, liver failure and inflammation. Also, HFD decreases testosterone and alters testis histological structure (seminiferous tubular degeneration, impaired spermatogenesis and interstitial fibrosis). Treatment of HFD rats with extract of S. balansae normalizes body weight and plasma parameters, increases testosterone and regenerates testicular structure and function. In summary, S. balansae could reduce metabolic complications induced by HFD and serve the basis for developing a new therapy for testicular dysfunction.