Administration Of High-fat Diet Research Articles

In vitro and in vivo antidiabetic activity of Tamarix stricta Boiss.: Role of autophagy

Ethnopharmacological relevanceType 2 diabetes mellitus (DM) is a complicated metabolic disorder with no definite treatment. Different species of the genus Tamarix (tamarisk) are used by local people to treat DM. Tamarix stricta Boiss. is an endemic species to Iran with several traditional therapeutic uses in Persian Medicine. This study aimed to assess the antidiabetic activity of T. stricta. Materials and methodsHydroethanolic extract of the plant was prepared and analyzed by High-performance liquid chromatography (HPLC). The protective effect of the extract was evaluated in streptozotocin (STZ)-induced toxicity and markers of autophagy in pancreatic RIN-5F cells. The effect of intragastric 10 or 20 mg/kg of the extract was compared with negative control (water) or positive control (metformin) treatment during four weeks of administration in high-fat diet + STZ-induced DM in Balb/c mice. ResultsResults showed the presence of 8.436 mg of gallic acid in each gram of the extract. A significant cytoprotective effect was observed by T. stricta in STZ-induced toxicity in RIN-5F cells, partially due to the modulation of autophagy. Also, animals treated with the extract showed a significant improvement in glycemic and lipid profiles, liver function, and histopathologic features of pancreas and liver compared with the negative control. ConclusionT. stricta demonstrated beneficial effects in animal model of DM; though, further studies are recommended to confirm the clinical use of this plant in DM.

The Effect of Dipeptidyl Peptidase-4 Inhibitors or Curcumin on Diet Induced Metabolic Syndrome with Cardiac Dysfunction in Rats

ABSTRACT Background: Metabolic syndrome (MS) increases the risk of developing cardiovascular diseases (CVDs) which are the leading cause of death worldwide. Objective: This study is aiming to investigate the curative effects ofdipeptidyl peptidase-4 inhibitorsand the prophylactic effects of curcumin on diet induced metabolic syndrome which is associated with cardiac dysfunction in rats. Methodology: sixty adult male albino rats were divided into six groups: Group I: (control). Group II: (MS induced). Group III: (Vildagliptin only). Group IV: (Curcumin only). Group V (therapeutic):Vildagliptin treated rats after 8 weeks of MS to the end of 12 weeks. Group VI (prophylactic): Curcumin is administered with MS induction concomitantly for 12 weeks. Transthoracic echocardiogram was done while rats were alive. At the end of the experiment, blood was collected and biochemical analysis (blood glucose, serum insulin, lipid profile and cardiac enzymes) was done. Heart tissues were used for oxidative stress parameters (cardiac mitochondrial reactive oxygen species (ROS) and cardiac mitochondrial complex I and complex II) beside histopathological examination. Results: High fat diet (HFD)administration resulted in a significant increase in blood glucose, serum insulin, homeostasis model assessment of IR (HOMA- IR) index with disturbed lipid profile. Significant increase in serum cardiac enzymes and oxidative stress tissue markers were also noticed. Echocardiography revealed structural and functional cardiomyopathy. Histopathological examination showed cellular infiltrations with fat cells and collagen fibers accumulation. DPP- 4 inhibitors and curcuminresulted in a significant decrease in glucose, insulin, and HOMA- IR index, partial amelioration of lipid profile, cardiac enzymes, and cardiac oxidative stress markers. Echocardiography revealed alleviation of cardiomyopathy. Histopathological examination also revealed highly manifested structural improvement. Conclusion: The current study revealed that both DPP- 4 inhibitors and curcumin improve cardiomyopathy resulted from HFD administration with a diversity of mechanisms including anti-inflammatory, anti-apoptotic and anti-oxidative ways.

Every-other day fasting prevents memory impairment induced by high fat-diet: Role of oxidative stress

Imbalance of diet consumption results in memory and learning deterioration. High-fat diet (HFD) causes neuronal damage and eventually cognitive impairment, which can be related to increasing oxidative stress in the brain. Using the every other day fasting (EODF) paradigm, as a method of dietary restriction is thought to provide protection of learning and memory in several experimental studies. In the current work, the preventive effect of EODF paradigm on memory impairment-induced by HFD was investigated. Adult male Wistar rats were fed with HFD using the EODF paradigm for six weeks. At the end of these six weeks, and while the previous treatment were continued, rats were examined for learning and memory (both the short-term and the long-term memory) using the radial arm water maze (RAWM). Oxidative stress in the brain, namely in the hippocampus was also assessed. Chronic administration of HFD induced impairment in both, short- and long- term memory that was prevented using EODF paradigm. Furthermore, EODF prevented HFD-induced decrease in the activities of the antioxidant enzymes, SOD and catalase along with reduction of glutathione (GSH) level and the ratio of reduced glutathione/oxidized glutathione (GSH/GSSG ratio). The EODF also inhibited rise in oxidized glutathione (GSSG) and thiobarbituric acid reactive substances (TBARS) seen with HFD. In conclusion, EODF ameliorated oxidative stress and memory impairment induced by chronic HFD. This probably, can be explained by the ability of EODF to normalize mechanisms involved in oxidative stress in the hippocampus.

Quercetin modulates AMPK/SIRT1/NF-κB signaling to inhibit inflammatory/oxidative stress responses in diabetic high fat diet-induced atherosclerosis in the rat carotid artery.

Inflammation and oxidative stress serve interrelated roles in the development of atherosclerosis and other vascular diseases. Quercetin has been previously reported to exhibit numerous beneficial properties towards several metabolic conditions and cardiovascular disease. The present study aimed to evaluate the effects of quercetin on the 5'adenosine monophosphate-activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/NF-κB signaling pathway and inflammatory/oxidative stress response in diabetic-induced atherosclerosis in the carotid artery of rats. Male Wistar rats were used to create a diabetes-induced atherosclerosis model by the administration of high fat diet (HFD) with streptozotocin, which lasted for 8 weeks. Control and diabetic rats received quercetin (30 mg/kg/day; orally) for the last 2 weeks of the diabetic period. Plasma lipid profile and vascular levels of oxidative stress markers, inflammatory cytokines, NF-κB signaling proteins and SIRT1 expression were evaluated using ELISA and western blotting. Quercetin treatment in HFD diabetic rats was reported to improve the lipid profile and reduce the number of atherosclerotic lesions, atherogenic index and malondialdehyde levels, whilst increasing the activity of enzymatic antioxidants in the carotid artery. Additionally, the inflammatory response was suppressed by quercetin administration, as indicated by the reduced NF-κB and IL-1β levels, and increased IL-10 levels. Furthermore, SIRT1 expression was revealed to be significantly increased in response to quercetin treatment compared with non-treated HFD rats. However, these effects of quercetin were abolished or reversed by the administration of compound-C (0.2 mg/kg), a specific AMPK blocker, in HFD rats. Therefore, quercetin may have promising potential in ameliorating atherosclerotic pathophysiology in the rat carotid artery by inhibiting oxidative stress and inflammatory responses mechanistically by modulating the AMPK/SIRT1/NF-κB signaling pathway.

Food-grade titanium dioxide (E171) induces anxiety, adenomas in colon and goblet cells hyperplasia in a regular diet model and microvesicular steatosis in a high fat diet model

Food-grade titanium dioxide (E171) is a white additive widely used in solid and liquid food products. There is still debate about E171 toxic effects after oral consumption since this additive is deposited in colon, liver, spleen, testis and brain. The consumption of E171 commonly occurs with Western diets that are characterized by a high fat content. Thus, E171 could worsen adverse effects associated with a high fat diet (HFD) such as anxiety, colon diseases and testicular damage. We aimed to evaluate the effects of E171 on anxiety-like behavior, colon, liver and testis and to analyze if the administration of a HFD could exacerbate adverse effects. E171 was administered at ~5 mg/kgbw by drinking water for 16 weeks and mice were fed with a Regular Diet or a HFD. E171 promoted anxiety, induced adenomas in colon, goblet cells hypertrophy and hyperplasia and mucins overexpression, but had no toxic effects on testicular tissue or spermatozoa in regular diet fed-mice. Additionally, E171 promoted microvesicular steatosis in liver in HFD fed-mice and the only HFD administration decreased the spermatozoa concentration and motility. In conclusion, E171 administration increases the number of adenomas in colon, induces hypertrophy and hyperplasia in goblet cells and microvesicular steatosis.

Treatment with isolated gold nanoparticles reverses brain damage caused by obesity

In this study, we performed two experiments. In the first experiment, the objective was to link gold nanoparticles (GNPs) with sodium diclofenac and/or soy lecithin and to determine their concentration in tissues and their toxicity using hepatic and renal analyzes in mice to evaluate their safety as therapeutic agents in the subsequent treatment of obesity. In the second experiment, we evaluated the effect of GNPs on inflammatory and biochemical parameters in obese mice. In the first experiment, we synthesized and characterized 18 nm GNPs that were administered intraperitoneally in isolation or in association with sodium diclofenac and/or soy lecithin in mice once daily for 1 or 14 days. Twenty-four hours after the single or final administration, the animals were euthanized, following which the tissues were removed for evaluating the concentration of GNPs, and serum samples were collected for hepatic and renal analysis. Hepatic damage was evaluated based on the levels of alanine aminotransferase (ALT), whereas renal damage was evaluated based on creatinine levels. A higher concentration of GNPs was detected in the tissues upon administration for 14 days, and there were no signs of hepatic or renal damage. In the second experiment, the mice were used as animal models of obesity and were fed a high-fat diet (obese group) and control diet (control group). After eight weeks of high-fat diet administration, the mice were treated with saline or with GNPs (average size of 18 nm) at a concentration of 70 mg/L (70 mg/kg) once a day, for 14 days, for 10 weeks. Body weight and food intake were measured frequently. After the experiment ended, the animals were euthanized, serum samples were collected for glucose and lipid profile analysis, the mesenteric fat content was weighed, and the brains were removed for inflammatory and biochemical analysis. In obese mice, although GNP administration did not reduce body and mesenteric fat weight, it reduced food intake. The glucose levels were reversed upon administration of GNPs, whereas the lipid profile was not altered in any of the groups. GNPs exerted a beneficial effect on inflammation and oxidative stress parameters, without reverting mitochondrial dysfunction. Our results indicate that the intraperitoneal administration of GNPs for 14 days results in a significant GNP concentration in adipose tissues, which could be an interesting finding for the treatment of inflammation associated with obesity. Based on the efficacy of GNPs in reducing dietary intake, inflammation, and oxidative stress, they can be considered potential alternative agents for the treatment of obesity.

Ketogenic Diet Elicits Antitumor Properties through Inducing Oxidative Stress, Inhibiting MMP-9 Expression, and Rebalancing M1/M2 Tumor-Associated Macrophage Phenotype in a Mouse Model of Colon Cancer.

Many advanced cancers are characterized by metabolic disorders. A dietary therapeutic strategy was proposed to inhibit tumor growth through administration of low-carbohydrate, average-protein, and high-fat diet, which is also known as ketogenic diet (KD). In vivo antitumor efficacy of KD on transplanted CT26+ tumor cells in BALB/c mice was investigated. The results showed that the KD group had significantly higher blood β-hydroxybutyrate and lower blood glucose levels when compared with the normal diet group. Meanwhile, KD increased intratumor oxidative stress, and TUNEL staining showed KD-induced apoptosis against tumor cells. Interestingly, the distribution of CD16/32+ and iNOS+ M1 tumor-associated macrophages (TAMs) increased in the KD-treated group, with concomitantly less arginase-1+ M2 TAMs. Moreover, KD treatment downregulated the protein expression of matrix metalloproteinase-9 in CT26+ tumor-bearing mice. Western blot analysis demonstrated that the expression levels of HDAC3/PKM2/NF-κB 65/p-Stat3 proteins were reduced in the KD-treated group. Taken together, our results indicated that KD can prevent the progression of colon tumor via inducing intratumor oxidative stress, inhibiting the expression of the MMP-9, and enhancing M2 to M1 TAM polarization. A novel potential mechanism was identified that KD can prevent the progression of colon cancer by regulating the expression of HDAC3/PKM2/NF-κB65/p-Stat3 axis.

Characterisation and Hypolipidaemic Activity of Phenylquinoline, and Narceine Isolated from Ficus polita Leaf

Aim: To evaluate hypolipidaemic potentials of column chromatography fractions (F1 to F6) of the chloroform leaf extract of Ficus polita and to detect the bioactive compounds present in the most active fraction using spectroscopic techniques.
 Study Design: Fourty-five (45) wistar rats were grouped into nine groups of five rats each: normal control, hyperlipidaemic control, hyperlipidaemic administered with standard drug control/ atorvastatin (10 mg/kg body weight), and hyperlipidaemic administered groups administered with 50 mg/kg body weight of column chromatography fractions (F1, F2, F3, F4, F5, and F6) for a period of two weeks.
 Place and Duration of Study: Department of Biochemistry Laboratory, Faculty of Basic Medical Sciences, Bayero University Kano, Nigeria, from May 2018 to April 2019.
 Methodology: Chloroform leaf extract of F. polita was fractionated by using column chromatography, and the resulting fractions were pooled, based on their retention factor (Rf), into six (6) fractions by using analytical thin layer chromatography. The resulting six (6) fractions were screened for hypolipidaemic activity. Serum total cholesterol (TC), triglycerides (TG), high density lipoprotein-cholesterol (HDL), and low density lipoprotein cholesterol (LDL) were determined. The rats treated with the best fraction in terms hypolipidaemic activity (fraction 3) were screened for serum HMG Co A reductase, lactate dehydrogenase (LDH), creatine kinase (CK) activities, as well as troponin I level. Oxidative stress markers such as malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) were determined in the heart tissue homogenate of the rats treated with fraction 3.
 Results: Fraction 3 treated hyperlipidaemic group showed significant (p<0.05) decrease in the levels of serum TC, TG, and LDL, but significant (p<0.05) increase in the level of serum HDL. Fraction 3 (F3) treated hyperlipidaemic groups showed significant (p<0.05) decrease in the activity of serum LDH and the level of troponin I, but significant (p<0.05) increase in the activity of serum HMG Co A reductase. After high fat diet administration, the level of heart tissue antioxidant markers such as GSH, SOD and catalase were decreased whereas the level of heart tissue MDA was elevated. The level of these antioxidant markers were brought to normalcy by fraction 3 (F3). Histological studies of the heart corroborated the biochemical findings, and treatment with fraction 3 (F3) was found to be effective in restoring dietary-induced myocardiac toxicity in rats. FTIR and GCMS analyses were carried out for the detection of bioactive compound(s) in fraction 3 (F3), and the result revealed the presence of "8-methoxy-4-phenylquinoline, and narceine.
 Conclusion: The study concludes that; the hypolipidaemic property of the leaf of F. polita is mediated by the bioactive compounds "8-methoxy-4-phenylquinoline, and narceine." via their antioxidant properties.

The Potential of Black Cumin (Nigella sativa, L.) Seeds Extract to Prevent Polyphagia and Weight Loss in Rattus Norvegicus of Diabetes Mellitus-Type 2

Patients of Diabetes Mellitus-type 2 (DM-2) is not only characterized by an increase of blood glucose levels, but also it is characterized by polyphagia and weight loss. This research aimed to discover the potential of 80% ethanol extract of Indonesia Nigella sativa L. (black cumin) seeds to the feed consumption level and changes in body weight of DM-2 rats model due to the administration of High Fat Diet (HFD) followed by the induction of streptozotocin (STZ) in a dose of 30 mg/kg Body Weight (BW). The DM-2 rats as the induction results divided into five groups, it was given a treatment using N. sativa extract with different doses, i.e. 0, 24, 48 and 72 mg/kg BW (DM-0, DM-24, DM-48, DM-72), positive control used metformin 45 mg/kg BW (DM-Metf). Non-DM rats (Normal) used as reasonable control. HFD induction carried out for 14 weeks, and N. sativa therapy conducted for four weeks after the oral glucose tolerance test. During the treatment, an observation of the feed consumption level and weekly weight gain were carried out. The data obtained were tested using one-way ANOVA, and it continued by Duncan Multiple Rank Test (DMRT), α= 5%. The research results indicated that the administration of 80% ethanol extract Indonesia N. sativa using the doses of 24 mg/kg BW and 48 mg/kg BW can control the feed consumption levels and prevent significant weight loss (p0.05)

Modulation of Renal Injury by Variable Expression of Myo-Inositol Oxygenase (MIOX) via Perturbation in Metabolic Sensors.

Obesity is associated with perturbations in cellular energy homeostasis and consequential renal injury leading to chronic renal disease (CKD). Myo-inositol oxygenase (MIOX), a tubular enzyme, alters redox balance and subsequent tubular injury in the settings of obesity. Mechanism(s) for such adverse changes remain enigmatic. Conceivably, MIOX accentuates renal injury via reducing expression/activity of metabolic sensors, which perturb mitochondrial dynamics and, if sustained, would ultimately contribute towards CKD. In this brief communication, we utilized MIOX-TG (Transgenic) and MIOXKO mice, and subjected them to high fat diet (HFD) administration. In addition, ob/ob and ob/MIOXKO mice of comparable age were used. Mice fed with HFD had increased MIOX expression and remarkable derangements in tubular injury biomarkers. Decreased expression of p-AMPKα (phospho AMP-activated protein kinase) in the tubules was also observed, and it was accentuated in MIOX-TG mice. Interestingly, ob/ob mice also had decreased p-AMPKα expression, which was restored in ob/MIOXKO mice. Parallel changes were observed in Sirt1/Sirt3 (silent mating type information regulation 2 homolog), and expression of other metabolic sensors, i.e., PGC-1α (Peroxisome proliferator-activated receptor gamma coactivator 1-alpha) and Yin Yang (YY-1). In vitro experiments with tubular cells subjected to palmitate-BSA and MIOX-siRNA had results in conformity with the in vivo observations. These findings link the biology of metabolic sensors to MIOX expression in impaired cellular energy homeostasis with exacerbation/amelioration of renal injury.

Polyphenols in Theobroma Cacao ameliorate microcirculation: In vivo intravital microscopic observation in rats

It has been reported that ingestion of cocoa or chocolate reduces blood pressure in the subjects with hypertension. To clarify the hypotensive activity of cocoa, we carried out the research on microcirculation using intravital microscopic technique. First, we estimated the influence of repeated treatment of cocoa on microcirculation. Male rats fed normal diet (ND) or 15% fat containing high fat diet (HFD) or 0.2% flavan-3-ols containing HFD for 6weeks. Under anesthesia, the arteriole function of mesentery in rat was observed under physiological condition. Vasocontraction induced by the phenylephlin was significantly reduced in the HFD group compared with that in ND group, there was not such change in the HFD with cocoa group. Endothelium dependent vasodilatation stimulated by acetylcholine was significantly decreased in the HFD group compared with that in ND group. On the other hand, endothelial dysfunction of arteriole induced by HFD was not shown in cocoa group. In addition, single oral administration of cocoa or its flavan 3-ols on microcirculation in skeletal muscle was estimated. Cocoa (100 mg/kg) or flavan-3-ols derived from cocoa (10 mg/kg) was administrated through a feeding tube to the animals, velocity of red blood cells in precapillary arteriole and the number of newly recruited capillary in cremaster muscle were significantly increased by the treatment of cocoa or flavon-3-ols compared with vehicle, accompany with elevation of heart rate and blood pressure. These research has revealed that the ingestion of cocoa improves endothelial dysfunction of arterioles which is major determining of blood pressure induced by the high fat diet and single oral administration of flavan 3-ols in cocoa altered microcirculation in skeletal muscle and general circulation. These acute effects might be related with the preventive action of flavan-3-ols on cardiovascular disease.

Evaluation of the neuro-protective effect of Artemisia judaica extract in a murine diabetic model.

Chronic hyperglycemia is associated with several negative outcomes including neuronal injury. Medicinal plants supplementation has been widely applied to treat or decrease diabetic complications. Here, the possible neuroprotective effect of Artemisia judaica extract (AjE. 300mgkg-1 day-1 ) against neuronal deficits in diabetes model induced by high-fat diet (HFD) administration and streptozotocin (STZ, 30mg/Kg) injection in rats was investigated. Diabetic rats showed a disturbance in the neuronal redox homeostasis as confirmed by the elevated lipoperoxidation and nitric oxide formation along with the decreased antioxidant molecules. In addition, a state of neuroinflammation and apoptosis were recorded in the brain tissue in diabetic rats. Furthermore, HFD/STZ provoked neurochemical alterations. However, AjE administration was found to abrogate significantly the neuronal impairments associated with diabetes. This neuroprotective effect comes from its strong antioxidant, anti-inflammatory, antiapoptotic, and neuromodulatory activity; suggesting that AjE may be applied to alleviate neurological impairments in diabetic patients. PRACTICAL APPLICATIONS: Diabetes mellitus (DM) is a metabolic disorder characterized by high blood glucose level comes from the dysregulation of insulin production and/or its action. The persisted hyperglycemia is correlated with the progression of several physical complications including renal, hepatic, vascular, retinal, and neuronal dysfunction. Artemisia is used in the nutritional and medicinal proposes due to the enriched bioactive molecules such as essential oil, flavonoids, phenolics, sesquiterpenoids, triterpenoids, and artemisinin. And we found that Artemisia judaica extract (AjE) administration was able to abrogate significantly the neuronal impairments associated with diabetes. This neuroprotective effect comes from its strong antioxidant, anti-inflammatory, anti-apoptotic and neuromodulatory activity; suggesting that AjE may be applied to alleviate neurological impairments in diabetic patients.

Deletion of Perilipin 5 Protects Against Hepatic Injury in Nonalcoholic Fatty Liver Disease via Missing Inflammasome Activation.

Nonalcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver diseases with an increasing prevalence due to rising rates of obesity, metabolic syndrome and type II diabetes. Untreated NAFLD may progress to steatohepatitis (NASH) and ultimately liver cirrhosis. NAFLD is characterized by lipid accumulation, and when sufficient excess lipids are obtained, irreversible liver injury may follow. Perilipin 5 (PLIN5), a known lipid droplet coating protein and triglyceride metabolism regulator, is highly expressed in oxidatively modified tissues but it is still unclear how it affects NAFLD/NASH progress. We here studied how PLIN5 affects NAFLD development induced by a 30-week high-fat diet (HFD) administration in wild type and PLIN5 knock out (Plin5−/−) mice. The disruption of PLIN5 induced differences in lipid metabolism during HFD feeding and was associated with reduced hepatic fat accumulation. Surprisingly, Plin5−/− mice showed mitigated activation of the NLR family pyrin domain-containing 3 (NLRP3) inflammasome, leading to minor hepatic damage. We conclude that PLIN5 is a pleiotropic regulator of hepatic homeostasis in NASH development. Targeting the PLIN5 expression appears critical for protecting the liver from inflammatory activation during chronic NAFLD.

Positive interaction of mangiferin with selected oral hypoglycemic drugs: a therapeutic strategy to alleviate diabetic nephropathy in experimental rats.

Diabetic nephropathy (DN) is one of the notorious diabetes associated complications. Despite many therapeutic strategies available, metabolic control of DN continues to poses a challenge. In this study, the interactions of mangiferin with selected oral hypoglycemic drugs, metformin and gliclazide to effectively alleviate the symptoms of renal injury in DN are evaluated. Male Sprague Dawley rats were used as experimental model and type II diabetes was induced by administration of high fat diet and low dose streptozotocin. Oral intervention of mangiferin with metformin and gliclazide for a period of 28days was given to diabetic rats. At the end of the treatment period, biochemical parameters, kidney function markers, anti-oxidant enzymes levels, oxidative stress mediated gene expression and histology were analysed. Significant reduction in the serum biochemical markers (glucose, urea and creatinine) were observed in the groups treated with combination drugs. Marked improvement in the combination treated groups in terms of inflammation and oxidative damage in the gene (TNFα, NFκB, TGFβ, VEGF, PKC) and protein expression (NFκB, VEGF) were noted in the kidney tissue alleviating the symptoms of DN. These results were further corroborated with histopathological results. Scientific data in the present study reveals that the combinations of mangiferin with the oral hypoglycemic drugs have been favorable in alleviating renal injury. Hence, a combination therapy to alleviate the vascular complication, diabetic nephropathy may be considered as a possible therapeutic strategy by including natural phytocompounds as an add on therapy to conventional oral hypoglycemic drugs.

Deletion of H-ferritin in macrophages alleviates obesity and diabetes induced by high-fat diet in mice.

Iron accumulation affects obesity and diabetes, both of which are ameliorated by iron reduction. Ferritin, an iron-storage protein, plays a crucial role in iron metabolism. H-ferritin exerts its cytoprotective action by reducing toxicity via its ferroxidase activity. We investigated the role of macrophage H-ferritin in obesity and diabetes. Conditional macrophage-specific H-ferritin (Fth, also known as Fth1) knockout (LysM-Cre Fth KO) mice were used and divided into four groups: wild-type (WT) and LysM-Cre Fth KO mice with normal diet (ND), and WT and LysM-Cre Fth KO mice with high-fat diet (HFD). These mice were analysed for characteristics of obesity and diabetes, tissue iron content, inflammation, oxidative stress, insulin sensitivity and metabolic measurements. RAW264.7 macrophage cells were used for in vitro experiments. Iron concentration reduced, and mRNA expression of ferroportin increased, in macrophages from LysM-Cre Fth KO mice. HFD-induced obesity was lower in LysM-Cre Fth KO mice than in WT mice at 12weeks (body weight: KO 34.6 ± 5.6g vs WT 40.1 ± 5.2g). mRNA expression of inflammatory cytokines and infiltrated macrophages and oxidative stress increased in the adipose tissue of HFD-fed WT mice, but was not elevated in HFD-fed LysM-Cre Fth KO mice. However, WT mice fed an HFD had elevated iron concentration in adipose tissue and spleen, which was not observed in LysM-Cre Fth KO mice fed an HFD (adipose tissue [μmol Fe/g protein]: KO 1496 ± 479 vs WT 2316 ± 866; spleen [μmol Fe/g protein]: KO 218 ± 54 vs WT 334 ± 83). Moreover, HFD administration impaired both glucose tolerance and insulin sensitivity in WT mice, which was ameliorated in LysM-Cre Fth KO mice. In addition, energy expenditure, mRNA expression of thermogenic genes, and body temperature were higher in KO mice with HFD than WT mice with HFD. In vitro experiments showed that iron content was reduced, and lipopolysaccharide-induced Tnf-α (also known as Tnf) mRNA upregulation was inhibited in a macrophage cell line transfected with Fth siRNA. Deletion of macrophage H-ferritin suppresses the inflammatory response by reducing intracellular iron levels, resulting in the prevention of HFD-induced obesity and diabetes. The findings from this study highlight macrophage iron levels as a potential therapeutic target for obesity and diabetes.

Anhuienoside C ameliorates atherosclerosis in rats via regulation of the NFκB/eNOS/NO signaling pathway

Purpose: To investigate the protective effect of anhuienoside C (AC) against high cholesterol dietinduced atherosclerosis in a rat model.
 Methods: Atherosclerosis was induced in rats by administration of high fat diet for 8 weeks, and AC (20 and 40 mg/kg) was administered orally. The effect of AC was determined by assessing serum lipid profiles and mediators of inflammation, as well as oxidative stress parameters in aortic tissue using enzyme-linked immunosorbent assay (ELISA). Western blot assay and reverse transcription polymerase chain reaction (RT-PCR) were used for the evaluation of protein expressions.
 Results: Serum levels of total cholesterol (TC), triglycerides (TGs), high density lipoprotein (HDL), low density lipoprotein (LDLP), and IL-1β, IL-18, TNF-α and NF-κB were significantly reduced in AC-treated group, relative to atherosclerotic rats (p < 0.01). Moreover, parameters of oxidative stress were attenuated in the aortic tissues of AC-treated group, when compared with atherosclerotic rats. There was significant increase in eNOS expression, and marked decrease in the expressions of MAPK and NF-kB protein in the aortic tissue homogenate of AC treated group, relative to atherosclerotic group (p <0.01). Treatment with AC attenuated the mRNA expressions of ICAM-1, VCAM-1 and MCP-1 in aortic tissue of the atherosclerotic rats.
 Conclusion: These results reveal that AC prevents atherosclerosis in rats by modulating the NFκB/eNOS/NO signaling pathway, and thus, can thus potentially be developed as anti-atherosclerotic agent.
 Keywords: Anhuienoside C, Atherosclerosis, Inflammation, Oxidative stress, Cholesterol

Letrozole Rat Model Mimics Human Polycystic Ovarian Syndrome and Changes in Insulin Signal Pathways.

BackgroundThe aim of this study was to explore whether letrozole and high-fat diets (HFD) can induce obese insulin-resistant polycystic ovary syndrome (PCOS) with all reproductive and metabolic phenotypes in a rat model.Material/MethodsTwenty-four 3-week-old female Sprague-Dawley rats were randomized into 4 groups: control, Letrozole, HFD, and Letrozol+HFD. The PCOS model was induced by 12 weeks of Letrozole treatment (1 mg/kg p.o. dissolved in 0.5% CMC solutions once daily) and HFD. Ovarian morphology, estrous cyclicity, hormonal status, body weight, glucose and insulin tolerance, lipid profile, and insulin signaling pathway were investigated.ResultsThe rat model manifests anovulatory cycles and PCO morphology, increased body weight, elevated testosterone levels, abnormal glucose and lipid metabolism, and insulin resistance. The rat model also expresses significantly decreased phosphorylation of 6 essential signaling proteins – INSR, IRS, PI3K, AKT, ERK1, ERK2 – in the PI3K/AKT and MAPK/ERK pathways in the classic insulin-sensitive tissues (e.g., quadriceps femoris muscle, omentum majus, and liver), as well as non-classic target ovary tissues. Disrupted insulin signaling contributes to the decrease in insulin sensitivity and compensatory hyperinsulinemia in PCOS rats.ConclusionsContinuous administration of letrozole and high-fat diets can induce PCOS, metabolic phenotypes, and disrupted activation of the insulin signaling pathway.

Anti-hypertensive effect of crocin and hesperidin combination in high-fat diet treated rats.

Cardiovascular diseases are the leading cause of death worldwide. Hypertension is the most important cause of such conditions. The use of medicinal herbs is of particular importance due to their lower cost and side effects. The aim of the present study was to compare the effect of hesperidin (HES) and crocin (CRO) alone and in combination, on blood pressure in a rat model of high-fat diet (HFD)-induced hypertension, using invasive carotid artery measurements. Animals were randomly assigned to the following groups: control group (received standard chow diet), HFD control group (received HFD containing 32% kcal of fat and 0.1% cholesterol), and three groups of HFD-treated animals that were treated with a single dose of CRO (20 mg/kg), HES (20 mg/kg), or CRO + HES (20 + 20 mg/kg). Except for the control group, rats received HFD for 7 weeks. On day 50, CRO, HES and normal saline were administered intraperitoneally and carotid arteries of the rats were cannulated. Three hours after the carotid artery cannulation, mean arterial blood pressure (MAP), systolic and diastolic blood pressure (SBP and DBP), and heart rate (HR) were measured using an intra-arterial catheter with the use of a Power Lab system. Data was analyzed using SPSS software. Rats that received HFD for 49 days presented a significant increase in SBP, HR and MAP compared to the control group (P<0.001). Whereas, HFD-treated rats of the CRO + HES group showed lower levels of SBP, HR and MAP; however, DBP remained unaffected. HES administration in HFD treated rats resulted in a significant decrease in SBP compared to the HFD control group with no significant differences in MAP. The hypotensive effects of the simultaneous administration of CRO and HES in HFD-hypertensive rats suggest the need for further study of these two natural products as a potential preventive measure against hypertension development, especially in patients with high normal blood pressure.

Toxic Effects of Chronic Exposure to High-Fat Diet and Arsenic on the Reproductive System of the Male Mouse

Objective: Obesity is associated with reproductive disorders. Arsenic disrupts male reproduction by direct effects on the male gonads or androgens secretion. So, the present study was conducted to evaluate the toxic effects of chronic concomitant administration of high-fat diet (HF) and arsenic on the reproductive system of the male mouse. Materials and methods: In this experimental study, 72 adult male mice were randomly divided into 6 groups: low-fat diet (LF0), LF+arsenic 25 ppm, LF+arsenic 50ppm, HF0, HF+arsenic 25 ppm and, HF+arsenic 50 ppm. 24 hours after the last experimental day, plasma samples, the cauda of epididymis and testis were prepared and removed for hormonal, sperm count and histopathological assessments. Results: Testis weight and volume increased in HF0 than other groups except for LF0. Plasma LH and testosterone levels decreased in LF50, HF0, HF25, and HF50 compared to LF0. A similar effect was observed in plasma FSH levels of HF0, HF25 and HF50 groups compared with LF0. Plasma level of estradiol increased in LF50 versus to other groups. Testosterone to estradiol ratio and sperm count decreased in all groups compared to LF0. Reduced interstitial cells and large numbers of vacuoles were observed in germinal epithelium of HF0 group, that these changes were more intense in both concentrations of arsenic-treated mice. Conclusion: Present study indicated that chronic exposure to HF and arsenic-induced hypogonadotropic hypogonadism concomitant with sperm count reduction and testicular damage.

Gymnemic acid, a potent antidiabetic agent protects skeletal muscle from hyperglycemia mediated oxidative stress and apoptotic events in High fat and High fructose diet fed adult rats

Type 2 diabetes is delineated by impaired metabolic flexibility, and intramyocellular lipid accumulation, causing insulin resistance, particularly in skeletal muscle by reducing insulin-stimulated glucose uptake. High-fat diet and high fructose (HFD and HF) administration in rodents bestows a model for hyperlipidemia, insulin resistance, and Type 2 diabetes. The current study is focused on elucidating the role of Gymnemic acid in combating hyperglycemia mediated oxidative stress and apoptotic events in the skeletal muscle of HFD and HF induced Type 2 diabetes in Wistar albino rats by boosting antioxidant defense system. Gymnemic acid, a saponin of triterpene glycoside contained in leaves of Gymnema Sylvestre, has potent anti-diabetic properties. Treatment with Gymnemic acid restored the antioxidant status (Gpx, SOD, CAT, GR, Vit C &amp; Vit E) with significant (p&lt;0.05) decrease in free radical levels and reinvigorated the expression of apoptotic and antiapoptotic proteins in Type 2 diabetic rats. Histopathological data demonstrate that oral administration of Gymnemic acid protects skeletal muscle fibers from an oxidative niche in HFD and HF in Type 2 diabetic rats. In accordance with this, Gymnemic acid might be regarded as a promising therapeutic agent against Type 2 diabetes, thereby restoring skeletal muscle integrity and function.