HFD Group Research Articles

Flavonoids by Ultrasonic-Assisted Extraction from Herbal Formulation of Zingiber officinale, Portulaca oleracea, and Tamarindus indica Improved Type 2 Diabetes in C57BL6/J Mice

Background: Diabetes is a problem of public health, in consequence, the increasing prevalence of both diseases needs more functional food products with efficiency and low cost to support treatment. Methods: Flavonoids from the herbal formulation of Portulaca oleracea, Zingiber officinale, and Tamarindus indica were extracted by ultrasound-assisted extraction technology, where several experiments were conducted to determine the implication of three independent variables on the higher production of flavonoids. Extraction time, ethanol concentration, and the liquid-solid ratio were determined as optimal conditions. Furthermore, flavonoids of interest in the extract were determined by using HPLC with UV/vis and mass spectrum and direct comparison reference compounds. Then was determined and compared the effect of extracts from P. oleracea (P), Z. officinale (Z), T. indica (T), and its combination (PTZ) on high-fat-diet-induced diabetic C57BL6/J mice. Results: The optimum conditions provided by the model include an extraction time of 30 min, an ethanol concentration of 50%, and a liquid/solid ratio of 40:1 mL/g, The antidiabetic effect of an extract rich in polyphenolic compounds was evaluated using streptozotocin (STZ) and a high-fat diet-induced diabetic mouse. Effect of extracts on high-fat-diet-induced diabetic mice including decreased FER, improved insulin sensitivity, fasting blood glucose, and serum lipid, and shown reducing body weight gain associated with a reduction of food intake. Extracts have protective effects on kidneys and liver improve lipolysis and successively decrease adipose tissue. Treatment with the polyherbal mixture has shown no toxic effects, possesses potent antihyperlipidemic, antihyperglycemic effects, and decreased glycated hemoglobin. The serum insulin level was significantly increased (p < 0.05) on the polyherbal extract treatment, supporting the evidence of β-cell re-establishment in the pancreas. reduce body weight and food intake, plasma adiponectin level increased while serum leptin level was significantly reduced compared with the HFD group. In addition, the activities of key enzymes of carbohydrate metabolism, antioxidant enzymes, lipid peroxidation markers, and glycogen content were also improved in diabetic mice. Conclusion: The combined form of P. oleracea, Z. officinale, and T. indica had better anti-diabetic properties compared to a single therapy, especially which could be related to their high content of phytochemicals in comparison with the bioactive content of a single plant. The results presented here indicated that the use of PTZ due to their synergistic effects can be useful against diabetes improving the factors associated with this disease.

Diversity of arterial cell and phenotypic heterogeneity induced by high-fat and high-cholesterol diet.

Lipid metabolism disorder is the basis of atherosclerotic lesions, in which cholesterol and low-density lipoprotein (LDL) is the main factor involved with the atherosclerotic development. A high-fat and high-cholesterol diet can lead to this disorder in the human body, thus accelerating the process of disease. The development of single-cell RNA sequencing in recent years has opened the possibility to unbiasedly map cellular heterogeneity with high throughput and high resolution; alterations mediated by a high-fat and high-cholesterol diet at the single-cell transcriptomic level can be explored with this mean afterward. We assessed the aortic arch of 16-week old Apoe-/- mice of two control groups (12weeks of chow diet) and two HFD groups (12weeks of high fat, high cholesterol diet) to process single-cell suspension and use single-cell RNA sequencing to anatomize the transcripts of 5,416 cells from the control group and 2,739 from the HFD group. Through unsupervised clustering, 14 cell types were divided and defined. Among these cells, the cellular heterogeneity exhibited in endothelial cells and immune cells is the most prominent. Subsequent screening delineated ten endothelial cell subsets with various function based on gene expression profiling. The distribution of endothelial cells and immune cells differs significantly between the control group versus the HFD one. The existence of pathways that inhibit atherosclerosis was found in both dysfunctional endothelial cells and foam cells. Our data provide a comprehensive transcriptional landscape of aortic arch cells and unravel the cellular heterogeneity brought by a high-fat and high-cholesterol diet. All these findings open new perspectives at the transcriptomic level to studying the pathology of atherosclerosis.

Impact of multiple different high-fat diets on metabolism, inflammatory markers, dysbiosis, and liver histology: study on NASH rat model induced diet

Background: The spectrum of non-alcoholic fatty liver disease (NAFLD), known as non-alcoholic steatohepatitis (NASH), can lead to advanced liver disease. It is known that a variety of diets play a significant role in the development of NAFLD/NASH. The goal of this study was to determine the most appropriate composition of diet to induce NASH in an animal model. Methods: This research used Rattus norvegicus strain Wistar (n=27), which were divided into four groups and given each diet for 12 weeks: normal diet (ND, n=7), high-fat diet (HFD, n=6), western diet (WD, n=7) and high-fat-high-fructose diet (HFHFD, n=7). Subjects were documented for body weight. Blood samples were taken for biochemical analysis: low-density lipoprotein (LDL), triglyceride, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), hepatic lipase, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and lipopolysaccharide (LPS). Feces were taken for short-chain fatty acid (SCFA) analysis. Liver histology was analyzed using NAS (NAFLD activity score). The comparison test was carried out using the one-way ANOVA or Kruskal–Wallis test. Results: The highest average body weight was in the WD group (346.14 g). Liver enzymes, LDL, triglyceride, propionic acid, and acetic acid in each group were not significantly different. TNF-α, IL-6, and hepatic lipase were significant (p = 0.000; p = 0.000; p = 0.004) and the highest was in the HFD group. Butyrate level was significant (p = 0.021) and the least was in the HFHFD group (4.77 mMol/g). Only WD and HFHFD had an NAS ≥ 5 (14% and 14%). The highest percentage of borderline NAS was found in WD (57%). Conclusions: The HFD group showed significant liver inflammation but did not produce NASH histologically, whereas the WD and HFHFD groups had the potential to develop NASH because the diets affected metabolic and inflammatory parameters as well as liver histology.

Brain N-Glycosylation and Lipidomic Profile Changes Induced by a High-Fat Diet in Dyslipidemic Hamsters.

The consumption of diets rich in saturated fats is known to be associated with higher mortality. The adoption of healthy habits, for instance adhering to a Mediterranean diet, has proved to exert a preventive effect towards cardiovascular diseases and dyslipidemia. Little is known about how a suboptimal diet can affect brain function, structure, and the mechanisms involved. The aims of this study were to examine how a high-fat diet can alter the brain N-glycan and lipid profile in male Golden Syrian hamsters and to evaluate the potential of a Mediterranean-like diet to reverse this situation. During twelve weeks, hamsters were fed a normal fat diet (CTRL group), a high-fat diet (HFD group), and a high-fat diet followed by a Mediterranean-like diet (MED group). Out of seventy-two identified N-glycans, fourteen were significant (p < 0.05) between HFD and CTRL groups, nine between MED and CTRL groups, and one between MED and HFD groups. Moreover, forty-nine lipids were altered between HFD and CTRL groups, seven between MED and CTRL groups, and five between MED and HFD groups. Our results suggest that brain N-glycan composition in high-fat diet-fed hamsters can produce events comparable to those found in some neurodegenerative diseases, and may promote brain ageing.

Effect of traditional herbal medicine, danggui-yukhwang-tang, on post-menopausal weight gain in ovariectomized high-fat diet rats

The decrease in estrogen due to menopause leads to impaired lipid metabolism and is closely related to the increase in metabolic syndrome due to weight gain. Hormone replacement therapy is effective for menopause, but with an increased risk of side effects. Danggui-yukhwang-tang (DYT) is a traditional drug, comprising seven herbs, used to treat diseases like slight fever with sweating, blood-flow disorders, and neurasthenia. However, the effect on menopausal obesity has not been reported. This study aimed to investigate the inhibitory effect of DYT on weight gain in female rats fed a high-fat diet after ovariectomy. Adipocyte differentiation was effectively reduced by DYT in 3T3-L1 cells, and the mRNAs of PPARγ, C/EBPα, and FABP4, which are adipogenesis-related genes, were reduced. In the in vivo study, OVX and HFD elevated body weight; however, its induction significantly decreased in the DYT-treated groups. The serum lipid profile was also examined, and DYT treatment significantly decreased LDL-cholesterol, triglyceride, and total cholesterol levels compared with the OVX and OVX + HFD groups. DYT treatment effectively reduced the temperature(s) of the tail and body in the rats. The study demonstrates that DYT inhibits adipogenic differentiation, hypercholesterolemia, and weight gain in a post-menopausal rat model by regulating adipogenic markers (PPARγ, C/EBPα, FABP4) and the serum lipid profile in OVX + HFD rats.

Dendrobium officinale polysaccharide prevents neuronal apoptosis via TET2-dependent DNA demethylation in high-fat diet-induced diabetic mice

Dendrobium officinale polysaccharide (DP) has the potential function to prevent diabetes-induced neuronal apoptosis, whereas the mechanism is not completely clear. Ten eleven translocation dioxygenase 2 (TET2) is one of the most important therapeutic target for repairing neuronal damage in diabetic mice. The aim of the present study was to investigate whether DP could prevent neuronal apoptosis by regulating TET2 in the brain of HFD-induced diabetic mice. C57BL/6J mice were randomly divided into four groups (n = 12), control group (CON), high-fat diet group (HFD, negative control), metformin group (MET, positive control), and DP group (DP). Compared with HFD group, the neuronal apoptosis of brain was significantly lower in the DP group. The levels of TET2 protein, 5-hydroxymethylcytosine (5hmC) and 5-formylcytosine (5fC) were significantly lower in the HFD group than in both the DP and CON groups in the cerebral cortex of mice. The ratio of p-AMPK/AMPK and α-KG/(fumaric acid + succinic acid) were significantly lower in the HFD group than in the other groups. The present study suggests that DP has a preventive effect on diabetes-induced neuronal apoptosis by regulating TET2 function through improving phosphorylate AMPK and mitochondrial function, thus remodeling DNA epigenetics profile of mice brain.

Identification of FGF13 as a Potential Biomarker and Target for Diagnosis of Impaired Glucose Tolerance.

Early identification of pre-diabetes provides an opportunity for intervention and treatment to delay its progression to type 2 diabetes mellitus (T2DM). We aimed to identify the biomarkers of impaired glucose tolerance (IGT) through bioinformatics analysis. The GSE76896 dataset, including non-diabetic (ND), IGT, and T2DM clinical samples, was deeply analyzed to identify 309 Co-DEGs for IGT and T2DM. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated that inflammatory responses and the PI3K-AKT signaling pathway are important patho-physiological features of IGT and T2DM. Protein-protein interaction (PPI) network analysis and cytoHubba technolgy identified seven hub genes: namely, CCL2, CXCL1, CXCL8, EDN1, FGF13, MMP1, and NGF. The expression and ROC curves of these hub genes were validated using the GSE38642 dataset. Through an immunofluorescence assay, we found that the expression of FGF13 in islets of mice in the HFD and T2DM groups was significantly lower than in the control group. Similarly, the level of FGF13 in the sera of IGT and T2DM patients was lower than that in the healthy group. Together, these results suggest that FGF13 can be treated as a novel biomarker of IGT, which may provide new targets for the diagnosis and treatment of pre-diabetes and T2DM.

Olive Leaves Extract and Oleuropein Improve Insulin Sensitivity in 3T3-L1 Cells and in High-Fat Diet-Treated Rats via PI3K/AkT Signaling Pathway.

Olive leaves extracts are known to exert potential pharmacological activities especially, antidiabetic and antiobesity. This study explores the anti-insulin resistant effect of olive leaves extracts and oleuropein in 3 T3-L1 cells and in high-fat diet fed rats. Our results showed that ethanol extract (EE) suppressed significantly (P < 0.01) triacylglycerol accumulation. In preadipocytes cells, EE 1/100 decreased cell viability and induced apoptosis. Real-time PCR analysis showed that EE reduced the mRNA levels of adipogenesis (CEBP-α, PPARγ, SREBP-1c, and FAS) and proinflammatory (TNF-α and IL-6) genes. Moreover, the cotreatment of EE 1/1000 or oleuropein with insulin increased considerably the expression of p-IRS, p85-pI3K, and p-AKT. In vivo model, the oral administration of oleuropein at 50 mg/kg in rats fed with high fat diet for 8 weeks reduced inflammation in liver and adipose tissues (WAT), improved glucose intolerance, and decreased hyperinsulinemia. Furthermore, the immunohistochemistry revealed that the expression level of p-Akt, IRS1, and Glut-4 were significantly enhanced in liver and WAT tissues after oleuropein supplementation comparing with that in HFD group. Additionally, the expression of IRS1 was markedly ameliorated in pancreas. Our obtained results can be adopted as an approach to used olive leaves as complement to prevent insulin-resistance disease.

Effect of virgin coconut oil on body weight, white fat depots, and biochemical and morphological parameters in mice fed standard or high-fat diets.

This study investigated the effects of virgin coconut oil (VCO) on body weight, white fat depots, and biochemical and morphological parameters in male Swiss mice fed standard (SD) or high-fat (HFD) diets. Thirty-three adult animals were assigned to one of four groups, as follows: SD, SD plus VCO (SDCO), HFD, and HFD plus VCO (HFDCO). VCO had no effects on the Lee index, subcutaneous fat, periepididymal fat, retroperitoneal fat, area under the curve for glucose, or pancreas weight, all of which were increased by HFD. Low-density lipoprotein cholesterol increased in the SDCO group compared with the SD group and decreased in the HFDCO group compared with the HFD group. VCO increased total cholesterol only in the SDCO group compared with the SD group, with no differences between the HFD and HFDCO groups. In conclusion, low-dose VCO supplementation did not improve obesity, had no effects on hepatic or renal function, and had beneficial effects on the lipid profile only in animals fed HFD.

Mentha canadensis attenuates adiposity and hepatic steatosis in high-fat diet-induced obese mice.

Obesity is a major risk factor for metabolic syndrome, a global public health problem. Mentha canadensis (MA), a traditional phytomedicine and dietary herb used for centuries, was the focus of this study to investigate its effects on obesity. Thirty-five male C57BL/6J mice were randomly divided into 2 groups and fed either a normal diet (ND, n = 10) or a high-fat diet (HFD, n = 25) for 4 weeks to induce obesity. After the obesity induction period, the HFD-fed mice were randomly separated into 2 groups: one group continued to be fed HFD (n = 15, HFD group), while the other group was fed HFD with 1.5% (w/w) MA ethanol extract (n = 10, MA group) for 13 weeks. The results showed that body and white adipose tissue (WAT) weights were significantly decreased in the MA-supplemented group compared to the HFD group. Additionally, MA supplementation enhanced energy expenditure, leading to improvements in plasma lipids, cytokines, hepatic steatosis, and fecal lipids. Furthermore, MA supplementation regulated lipid-metabolism-related enzyme activity and gene expression, thereby suppressing lipid accumulation in the WAT and liver. These findings indicate that MA has the potential to improve diet-induced obesity and its associated complications, including adiposity, dyslipidemia, hepatic steatosis, and inflammation.

Black and Yellow Soybean Consumption Prevents High-Fat Diet-Induced Obesity by Regulating Lipid Metabolism in C57BL/6 Mice.

To evaluate the antiobesity effects of yellow and black soybean, C57BL/6 mice were provided with a normal diet, high-fat diet, HFD-containing yellow soybean powder (YS), and black soybean powder (BS) for six weeks. Compared with the HFD group, both YS and BS decreased body weight by 30.1% and 37.2% and fat in tissue by 33.3% and 55.8%, respectively. Simultaneously, both soybeans significantly reduced the serum triglyceride and total cholesterol levels and regulated the lipogenic mRNA expressions of Pparγ, Acc, and Fas genes in the liver, supporting reduced body adiposity. Furthermore, BS significantly increased Pgc-1α and Ucp1 mRNA expression levels in epididymal adipose tissue, indicating thermogenesis is the key mechanism of BS. Taken together, our findings suggest that both soybeans prevent high-fat diet-induced obesity in mice by regulating lipid metabolism, and BS, in particular, has a greater antiobesity potential than YS.

Vitamin D supplementation and cardiac tissue inflammation in obese rats

ObjectiveThe current study was aimed to evaluate the effects of active form of vitamin D on TGF- β, NF-κB and MCP-1 in heart tissue of obese rats.MethodsForty rats were allocated into groups of normal diet and high fat diet for sixteen weeks; then each group was divided into two groups that received either 500 IU/kg vitamin D or placebo for five weeks. Biochemical parameters were assessed by ELISA kits.ResultsVitamin D reduced TGF-β in obese rats supplemented with vitamin D compared with other groups (P = 0.03). Moreover, vitamin D reduced MCP-1 concentrations in the heart tissues of both vitamin D administered groups compared to placebo one (P = 0.002). NF-κB in the heart of HFD + vitamin D group was significantly lower (P = 0.03). Current study also showed that vitamin D improves glycemic status and reduce insulin resistance significantly in HFD group (P = 0.008).ConclusionVitamin D was a potential anti- inflammatory mediator of cardiovascular disease and markers of glycemic status in obese rats. Further investigations are needed to better identify the therapeutic role of this vitamin in CVD and to elucidate the underlying mechanisms.

Studying the Pharmagenomic effect of Portulaca oleracea extract on anti-diabetic therapy using the Collaborative Cross mice

BackgroundPortulaca oleracea L. (PO) is a herb widely used in folk medicine as antioxidant and mainly as an anti-diabetic. However, scientific evidence of its effects remains very limited. Here we aim to unravel the effect of the host genetic background on the PO treatment in the development of obesity and type 2 diabetes (T2D) using the genetically diverse Collaborative Cross (CC) mouse model, which could contribute to better understand and design personalized medical treatment. ResultsWe have studied the PO treatments efficacy on reduction of body weight (BW) and glucose tolerance ability in 221 mice of 13 different CC lines as a response to two different diets: the control match diet (CMD – 10% fat) as a control group and the high-fat diet (HFD – 60% fat) as the experiment group. Glucose tolerance ability was determined by a 180 minutes Intraperitoneal Glucose Tolerance Test (IPGTT) and the calculation of the area under the curve (AUC) was made. PO treatments started in week 12 of the dietary challenge and lasted for 4 weeks. PO was given to the mice every other day by intraperitoneal (IP) injection at concentration of 200mg/kg. The results showed significant sex effect across the different lines and assessed traits; therefore, male and female mice data was analyzed separately. Sex differences among lines were analyzed by ANOVA and shown to be significant (P <0.05) for BW and IPGTT-AUC in three time points: initial time point, after three months of dietary challenge and when PO treatment completed. Additionally, the results showed a significant increase in BW for both female and males maintained on HFD and CMD for 12 weeks period. Furthermore, significant increase in Total AUC values for both sexes maintained on HFD was showed while mice maintained on CMD did not develop any insulin resistance keeping their glucose levels slightly lower than the initial time point. Thenceforth, a four weeks of PO treatment showed a significant decrease in glucose levels in the HFD group, presenting that male mice were more sensitive to the treatment than females. Furthermore, PO treatment seemed to affect female mice fed with CMD rather than male mice maintained on the same diet. ConclusionsOur findings confirm the effect of PO treatment as an antidiabetic agent due to its significant effect in reducing glucose levels in CC mice that developed T2D induced by HFD. Additionally, a stabilizing effect on body weight as a response to PO treatment was shown. Variations among the different CC lines might be explained by differences in host genetics. Further studies can provide a base for a pharmacogenetics approach to treat T2D.

High Fat Diet and Low Dose Streptozotocin Induced Diabetic Dyslipidaemia and Hepatic Damage in Rats

The objective of the present study was to validate a rat model of diabetic dyslipidaemia along with hepatic damage by High fat diet and low dose streptozotocin combination that resembles the natural history of metabolic syndrome in humans. Male and Female Sprague Dawley rats were divided into 2 groups. One group of rats fed with high fat diet and other group was fed with normal pellet diet for a period of 2 weeks followed by streptozotocin administration on 15th day. Body weight of the animals was measured on day 0, 14 and 21, also post 1 week of the streptozotocin administration the blood glucose, serum lipid, liver, kidney markers and insulin levels were measured. The high fat diet fed animals had exhibited a significant increase in body weight post two weeks of HFD feeding, but the body weight was reduced post 1 week of streptozotocin intervention due to metabolic disruption caused by STZ. The HFD group animals exhibited significant increase in blood glucose, serum total cholesterol, triglycerides, LDL, VLDL. Similarly, a significant decrease in HDL and serum insulin levels were observed as compared to the NPD fed animals. Further the HFD group animals had shown significant elevation of the liver function enzymes such as ALT and ALP levels as compared to the NPD fed animals. The present study confirms the experimental induction of diabetic dyslipidaemia along with hepatic damage which serves as an ideal model for metabolic syndrome along with hepatic cirrhosis which would useful for evaluating the therapeutic agents against type 2 diabetes, hyperlipidaemia and hepatic cirrhosis.

Distinct subcellular localisation of intramyocellular lipids and reduced PKCε/PKCθ activity preserve muscle insulin sensitivity in exercise-trained mice.

Athletes exhibit increased muscle insulin sensitivity, despite increased intramuscular triacylglycerol content. This phenomenon has been coined the 'athlete's paradox' and is poorly understood. Recent findings suggest that the subcellular distribution of sn-1,2-diacylglycerols (DAGs) in the plasma membrane leading to activation of novel protein kinase Cs (PKCs) is a crucial pathway to inducing insulin resistance. Here, we hypothesised that regular aerobic exercise would preserve muscle insulin sensitivity by preventing increases in plasma membrane sn-1,2-DAGs and activation of PKCε and PKCθ despite promoting increases in muscle triacylglycerol content. C57BL/6J mice were allocated to three groups (regular chow feeding [RC]; high-fat diet feeding [HFD]; RC feeding and running wheel exercise [RC-EXE]). We used a novel LC-MS/MS/cellular fractionation method to assess DAG stereoisomers in five subcellular compartments (plasma membrane [PM], endoplasmic reticulum, mitochondria, lipid droplets and cytosol) in the skeletal muscle. We found that the HFD group had a greater content of sn-DAGs and ceramides in multiple subcellular compartments compared with the RC mice, which was associated with an increase in PKCε and PKCθ translocation. However, the RC-EXE mice showed, of particular note, a reduction in PM sn-1,2-DAG and ceramide content when compared with HFD mice. Consistent with the PM sn-1,2-DAG-novel PKC hypothesis, we observed an increase in phosphorylation of threonine1150 on the insulin receptor kinase (IRKT1150), and reductions in insulin-stimulated IRKY1162 phosphorylation and IRS-1-associated phosphoinositide 3-kinase activity in HFD compared with RC and RC-EXE mice, which are sites of PKCε and PKCθ action, respectively. These results demonstrate that lower PKCθ/PKCε activity and sn-1,2-DAG content, especially in the PM compartment, can explain the preserved muscle insulin sensitivity in RC-EXE mice.

Alternate-Day High Fat-Normal Chow Diet Ameliorates HFD-Induced Obesity and Restores Intestinal Immunity.

To investigate the effect of alternating-day diet regimens on high-fat diet-induced metabolic disorders in mice. Eight-week-old C57BL/6J mice were fed with either a continuous normal chow diet (CD, n = 10), a continuous high-fat diet (HFD, n = 10), HFD alternating every 24 h with fasting (H-ADF, n = 20), or HFD alternating every 24 h with chow diet (H-ADC, n = 20) for 12 weeks. Weights were recorded weekly and oral glucose tolerance tests were performed 6 weeks after initiating the regimens. At the end of the study, blood samples were collected and serum insulin and lipids were measured; tissues were collected for histology and RNA-seq analysis. HFD significantly increased body weight and fat percentage, while HFD alternating with fasting or CD did not significantly affect body weight and fat percentage. The glucose intolerance induced by HFD was also significantly ameliorated in these two diet intervention groups. HFD-induced elevation of total cholesterol, low-density lipoprotein and insulin were also reduced in H-ADF and H-ADC groups. Moreover, HFD-disturbed immunity, presented by Lysozyme C-1 (Lyz1) immunostaining and RNA-seq, was restored in both alternating-regimen groups, especially, with H-ADC. At the transcriptional level, some cell proliferation and lipid absorption pathways were down-regulated in both H-ADF and H-ADC groups compared to the continuous HFD group. Alternating an HFD with a normal diet every 24 h effectively controls weight and prevents metabolic disorders and may act by affecting both fat absorption and intestinal immunity.

Achyranthes Aspera Root Extract Attenuates the Damage Caused by High Fat Diet and Streptozotocin-Induced Diabetes in Wistar Rats

Achyranthes aspera is an herb found in the Indian subcontinent and has been used for decades because of its traditional anti-diabetic and antiobesity properties. Since studies are not reported on Achyranthes aspera protection in high-fat diet and diabetes-induced animal models, our aim was to investigate the protective effect of root extract of Achyranthesaspera on the combined effect of high-fat diet and streptozotocin-induced biochemical changes in Wistar rats. To achieve this aim, the objectives of the study were to estimate the body weight, serum glucose, insulin, Glycated hemoglobin(HbA1c), Homeostatic Model Assessment of Insulin Resistance (HOMA- IR), serum lipid profile, and liver glycogen among the Wistar rats which were divided into 6 groups having 6 rats in each group. Group 1 - control rats Group 2 - diabetic group rats, Group 3 – HFD diabetic rats and the rats from groups 4 to 6 were given a high-fat diet+ Streptozotocin 40 mg/kg + a low dose of root extract of Achyranthes aspera (250 mg/kg), high dose of root extract of Achyranthe saspera (500 mg/kg), metformin (250 mg/kg), respectively treated for 35 days. Body weight followed by serum glucose, insulin, HBA1C, HOMA- IR, serum lipid profile, and liver glycogen were evaluated. HFD + Diabetic group showed an elevated level of lipid profile and alterations in serum glucose, HbA1C, HOMAIR, Insulin and liver glycogen. Administration of Metformin and hydro alcoholic root extract of Achyranthes aspera500 mg/kg to HFD + diabetic group protected the biochemical alterations and serum insulin, glucose levels, HbA1c, HOMA- IR, liver glycogen. In comparison with HFD group, there was 1.76,2.02, and,1.3-fold decrease in Glucose levels in HFD+STZ+ Metformin, HFD+STZ+HEAA250, and HFD+STZ+HEAA500 groups respectively. In comparison with HFD group, there was a 1.38,1.15 and,1.59-fold increase in Insulin levels in HFD+STZ+ Metformin, HFD+STZ+HEAA250, and HFD+STZ+HEAA500 groups respectively. The HbA1C levels (mean±SEM) of control, STZ, HFD+STZ, HFD+STZ+ Metformin, HFD+STZ+HEAA250, and HFD+STZ+HEAA500 were 7.36±0.22,10.18±0.74,8.94±0.33,8.10±0.22,8.94±0.22 and 7.0±0.41 respectively. The HOMA-IR levels (mean±SEM) of control, STZ, HFD+STZ, HFD+STZ+ Metformin, HFD+STZ+HEAA250, andHFD+STZ+HEAA500were 2.08±0.12,3.99±0.85,17.05±3.53,1.61±0.28,2.46±0.74 and 2.01±0.20 respectively The study findings reveal the protective role of Achyranthesaspera on high-fat diet and a diabetic induced biochemical changes.

Zuogui-Jiangtang-Qinggan-Fang alleviates high-fat diet-induced type 2 diabetes mellitus with non-alcoholic fatty liver disease by modulating gut microbiome-metabolites-short chain fatty acid composition

Non-alcoholic fatty liver disease (NAFLD) pathogenesis is affected by dysbiosis of the gut microbiome and the metabolites it generates. Therefore, restoring the equilibrium between the gut microbiome and the generated metabolites may have therapeutic potential for the syndrome. Zuogui Jiangtang Qinggan Fang (ZGJTQGF) is a Chinese herbal formulation used clinically to treat type 2 diabetic mellitus (T2DM) and fatty liver disease. However, its pharmacological mechanisms have not been well characterized. This work aimed to evaluate the hepatoprotective mechanism of ZGJTQGF in T2DM with NAFLD mice by incorporating gut microbiota, short-chain fatty acids（SCFAs）, and metabolomic analysis, and then to provide strong support for clinical treatment of T2DM with NAFLD. The sequencing of 16 S rRNA revealed that ZGJTQGF therapy modified the composition and abundance of the gut microbiome, raised the level of SCFAs, and restored the intestinal mucosal barrier. The non-targeted metabolomic analysis of liver tissues identified 212 compounds, of which108 were differentially expressed between the HFD and ZGJTQGF groups. Moreover, L-glutamic acid, L-Phenylalanine, Glycine, Taurine, Deoxycholic acid, and citric acid levels were also considerably altered by ZGJTQGF. Our findings suggest that ZGJTQGF ameliorates HFD-induced hepatic steatosis by modulating the gut microbiota composition and its metabolites and boosting the levels of SCFAs. More notably, ZGJTQGF may be a promising medication for preventing and treating NAFLD.

The association between obesity and vitamin D deficiency modifies the progression of kidney disease after ischemia/reperfusion injury.

Acute kidney injury (AKI) alters renal hemodynamics, leading to tubular injury, activating pathways of inflammation, proliferation, and cell death. The initial damage caused to renal tissue after an ischemia/reperfusion (I/R) injury exerts an important role in the pathogenesis of the course of AKI, as well as in the predisposition to chronic kidney disease. Vitamin D deficiency has been considered a risk factor for kidney disease and it is associated with tubulointerstitial damage, contributing to the progression of kidney disease. Obesity is directly related to diabetes mellitus and hypertension, the main metabolic disorders responsible for the progression of kidney disease. Furthermore, the expansion of adipose tissue is described as an important factor for increased secretion of pro-inflammatory cytokines and their respective influence on the progression of kidney disease. We aimed to investigate the influence of vitamin D deficiency and obesity on the progression of renal disease in a murine model of renal I/R. Male Wistar rats underwent renal I/R surgery on day 45 and followed until day 90 of the protocol. We allocated the animals to four groups according to each diet received: standard (SD), vitamin D-depleted (VDD), high fat (HFD), or high fat vitamin D-depleted (HFDV). At the end of 90 days, we observed almost undetectable levels of vitamin D in the VDD and HFDV groups. In addition, HFD and HFDV groups presented alterations in the anthropometric and metabolic profile. The combination of vitamin D deficiency and obesity contributed to alterations of functional and hemodynamic parameters observed in the HFDV group. Moreover, this combination favored the exacerbation of the inflammatory process and the renal expression of extracellular matrix proteins and phenotypic alteration markers, resulting in an enlargement of the tubulointerstitial compartment. All these changes were associated with an increased renal expression of transforming growth factor β and reduced expression of the vitamin D receptor. Our results show that the synergistic effect of obesity and vitamin D deficiency exacerbated the hemodynamic and morphological changes present in the evolution of renal disease induced by I/R.

Sodium Alginate Prevents Non-Alcoholic Fatty Liver Disease by Modulating the Gut-Liver Axis in High-Fat Diet-Fed Rats.

Previous studies have suggested that the sodium alginate (SA) is beneficial for the treatment of non-alcoholic fatty liver disease (NAFLD), while the potential mechanisms are largely unknown. The present study aimed to clarify the effects and potential mechanisms of SA in preventing NAFLD via the gut-liver axis. Thirty-two male Sprague-Dawley rats were randomly divided into four groups: normal control group (NC); high-fat diet group (HFD); HFD with 50 mg/kg/d sodium alginate group (LSA); HFD with 150 mg/kg/d sodium alginate group (HSA). After 16 weeks, the rats were scarified to collect blood and tissues. The results indicated that SA significantly reduced their body weight, hepatic steatosis, serum triglyceride (TG), alanine transaminase (ALT) and tumor necrosis factor α (TNF-α) levels and increased serum high-density lipoprotein-cholesterol (HDL-C) levels in comparison with HFD group (p &lt; 0.05). The elevated mRNA and protein expression of genes related to the toll-like receptor 4 (TLR-4)/nuclear factor-kappa B (NF-κB)/nod-like receptor protein 3 (NLRP3) inflammatory signaling pathway in the liver of HFD-fed rats was notably suppressed by SA. In terms of the gut microbiota, the LSA group showed a significantly higher fecal abundance of Oscillospiraceae_UCG_005, Butyricicoccaceae_UCG_009 and Colidextribacter compared with the HFD group (p &lt; 0.05). The rats in the HSA group had a higher abundance of unclassified_Lachnospiraceae, Colidextribacter and Oscillibacter compared with the HFD-associated gut community (p &lt; 0.05). In addition, rats treated with SA showed a significant increase in fecal short chain fatty acids (SCFAs) levels and a decline in serum lipopolysaccharide (LPS) levels compared with the HFD group (p &lt; 0.05). Moreover, the modulated bacteria and microbial metabolites were notably correlated with the amelioration of NAFLD-related indices and activation of the hepatic TLR4/NF-κB/NLRP3 pathway. In conclusion, SA prevented NAFLD and the potential mechanism was related to the modulation of the gut-liver axis.