Biochemical and Metabolic Implications of Tricarboxylic Acids and their Transporters

Tricarboxylic acid cycle is the essential metabolic pathway for cellular biosynthetic processes e.g. gluconeogenesis, amino acid and heme biosynthesis. Exploring the functional regulatory mechanism of the tricarboxylate transporters, especially the mitochondrial inner membrane transporters of liver, has received much attention due to their implications on various metabolomic diseases. The tricarboxylic acid transporter has been purified from liver with molecular weight 32.6 kDa. Based on the amino acid sequence analysis, six hypothetical membrane-spanning alpha helices have been recognized and used for development of an initial model for protein topographical, and modelling analyses of the tricarboxylate transporter within the inner membrane. The objective of this review was to emphasize the biochemical and metabolic implications of tricarboxylic acids especially citric, aconitic and itaconic acids and their transporters on the mitochondrial membrane of liver

Ameliorative Effect of Ketogenic Diet on High Fat Diet Induced Metabolic Syndrome in Rats Via GLP-1R and PGC-1α

Metabolic syndrome (MetS) is a kind of metabolic disorder, including abdominal obesity, hyperglycemia, dyslipidemia, hypertension, etc.  Dietary intervention was thought to be one of the lifestyle strategies, along with others like nutritional intervention, psychological intervention, etc., that might effectively treat MetS. the ketogenic diet (KD) is a high-fat diet that has been shown to be helpful in a variety of diseases such as polycystic ovarian syndrome, acne, cancer, and respiratory distress. The study was conducted to investigate the therapeutic potential of a ketogenic diet on rat MetS models. In this study, 40 males’ rats were divided into four groups, for a period of 24 weeks, the rats were received KD. Some biochemical, molecular parameters and histopathology of liver tissues were determined. Our results demonstrated that compared to rats in the MetS group, the KD group and MetS +KD group reduced glucose, insulin, HOMA-IR, alanine aminotransferase (ALT), aspartate aminotransferase (AST), Alkaline phosphatase (ALP) levels and Malondialdehyde (MDA), while the KD group and MetS +KD group increased glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) levels (P < 0.05). An upregulation was found in the gene expression levels of the homogenate of Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and the Glucagon-like peptide-1 receptor (GLP-1R) in control group, KD group, and MetS +KD group compared with Mets group. In conclusion based on these results, KD can be suggested as a healthy weight loss diet with positive metabolic and hepatic benefits

Anti-obesity Effects of Foods Producing Hydrogen Sulfide in Rats Fed a High-Fructose Diet

The goal of this research was to determine the impact of garlic oil and leek powder on serum lipid levels and on sonic hedgehog (SHH) signalling pathway in a rat model of hyperlipidemia, to offer evidence supporting the use of diet as a means of preventing hyperlipidemia, and to further investigate the possible health advantages of these two H2S-donors. In this study, 80 males Wistar rats were divided into eight groups, for a period of 18 weeks, the rats were orally dosed with garlic oil and leek powder. Obesity indicators, serum lipid levels, some biochemical, molecular parameters and histopathology of liver tissues were determined. Compared to rats in the obese model groups, the garlic oil and leek powder reduced cholesterol, triacylglycerol, low-density lipoprotein-cholesterol (LDL-c) and very low density lipoprotein-cholesterol (VLDL-c) levels in the serum (P < 0.05). The garlic oil and leek powder also helped reduce hepatic steatosis and enhance lipid profiles. A reduction was found in the gene expression in the hepatic homogenate of Patched 1 (Ptch1), smoothened (SMO), glioma-associated oncogene homolog 1 (GLI 1), Sonic hedgehog protein (SHH), Toll-like receptor 4 (TLR 4), and nuclear factor kappa kB (NF-kB). On the other hand, there was a significant upregulation in the mRNA expression of hedgehog-interacting protein (Hhip-1), and miRNA 26a which is also a dose- and time-dependent manner. The obtained findings suggested that both garlic oil and leek powder as H2S donor had anti-obesity capabilities that can mitigate the effects of an HFD

The Metabolic Impact of Vitamin D on the Context of Metabolic Syndrome

Vitamin D deficiency is one of the major affecting factors on metabolic syndrome, cancer, cardiovascular diseases, and type 2 diabetes mellitus. So we aimed in our study to show the anti-diabetic effects of vitamin D on type 2 diabetic rats. Therefore, 45 rats were divided into three groups (15 rats per each group). The first group served as a control and fed on a standard chow diet while the other two groups served as diabetic groups as they fed on high fructose, high fat, and high sucrose diet and for 12 weeks then they injected with intraperitoneal single dose (45 mg/kg b.wt) of STZ dissolved in cold 0.01 M citrate buffer (pH 4.5) to develop type 2 diabetes mellitus. After one week of injection the third diabetic group was treated for 4 weeks with two intramuscular (20,000 IU/Kg) of vitamin D dissolved in sesame oil. The obtained results demonstrated that administration of vitamin D could improve serum glucose and insulin levels with an increase in serum calcitonin and calcium in correlation with the decrease in parathyroid hormone, phosphorus and lipids levels in the presence of significant upregulation of gene expression in liver (PPARα, GLP-1, and IGF-1) and in adipose tissue (Ptch, Smo, Gli-1, and hhip). In conclusion, vitamin D administration can improve insulin resistance by improving blood glucose and insulin levels

Dexpanthenol improved stem cells against cisplatin-induced kidney injury by inhibition of TNF-α, TGFβ-1, β-catenin, and fibronectin pathways

Introduction: Cisplatin interacts with DNA and induces an immunological response and reactive oxygen species, which are nephrotoxic mediators. Stem cells self-renew through symmetric divisions and can develop into other cell types due to their multipotency. Dexpanthenol has been proven to protect against renal injury. Aim: This study aims to demonstrate that dexpanthenol could improve the effect of adipose-derived mesenchymal stem cells (ADMSC) against cisplatin-induced acute kidney injury. Methods: Sixty male Sprague-Dawley rats were divided into 5 groups (N = 12): control, cisplatin, cisplatin & dexpanthenol, cisplatin & ADMSC, and cisplatin & dexpanthenol & ADMSCs. On the 5th day following cisplatin injection, half the rats in each group were sacrificed, and the other half were sacrificed on the 12th day. Histopathological examination, molecular studies (IL-6, Bcl2, TGFβ-1, Caspase-3, Fibronectin, and β-catenin), antioxidants (superoxide dismutase and catalase), and renal function were all investigated. Results: In contrast to cisplatin group, the dexpanthenol and ADMSCs treatments significantly decreased renal function and oxidative stress while significantly enhancing antioxidants. Dexpanthenol improved stem cells by significantly down-regulating caspase-3, IL-6, TGF-β1, Fibronectin, and β-catenin and significantly up-regulating Bcl2 and CD34, which reversed the cisplatin effect. Conclusion: Dexpanthenol enhanced ADMSCs' ability to protect against cisplatin-induced AKI by decreasing inflammation, apoptosis, and fibrosis

The Metabolic Impact of Vitamin B12 in The Context of Metabolic Syndrome

Metabolic syndrome (Mets) refers to a group of symptoms that increasing the risk of heart disease, stroke and type 2 diabetes (T2DM). One of the most difficult health issues facing the world today is diabetes mellitus (DM). In diabetes, chronic hyperglycemia can cause both immediate and delayed consequences. Cobalamin, or vitamin B12, is a water-soluble vitamin essential for proper neuronal and vascular function, normal hemopoiesis, and DNA synthesis. The aim of this study was to determine the impact of vitamin B12 in the streptozotocin (STZ)-induced diabetic rats. In this study, 30 males’ rats were divided into three groups, for a period of 9 weeks, the rats were injected with vitamin B12. Serum lipid levels, some biochemical, molecular parameters and histopathology of liver and brain tissues were determined. Our results demonstrated that compared to rats in the diabetic groups, the vitamin B12 reduced glucose, insulin, HOMA-IR, glycated haemoglobin (HbA1c), cholesterol, triacylglycerol (TAG), high density lipoprotein-cholesterol (HDL-c), low-density lipoprotein-cholesterol (LDL-c) levels, and Malondialdehyde (MDA), while vitamin B12 increased vitamin 12, glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) levels (P < 0.05). An upregulation was found in the gene expression in the homogenate of hepatocyte growth factor (HGF), leptin receptor (LEPR), and glucose transporter -2 (GLUT-2). On the other hand, there was a significant downregulation in the mRNA expression of Janus kinase3 (JAK3), signal transducer and activator of transcription3 (STAT3), Transforming growth factor–β (TGF-β), and protein tyrosine phosphatase 1B (PTPN1). In conclusion our findings suggested that vitamin B12 supplementation can mitigate the Impact of an STZ in diabetic rats. This new research provides further evidence that vitamin B12 may be useful as a treatment for diabetes

Hydrogen Sulfide Ameliorative Role in Induced Diabetes in Rat by Regulating Endoplasmic Reticulum Stress Signaling and miRNA-27a

The present study was carried out to investigate the effects of garlic (Allium sativum Linn) and leek (Allium porrum L.) on biochemical parameters, lipid profile and gene expression in high fructose diet (HDF)- induced diabetes in rat. In this study, we used 80 males Wistar rats for 18 weeks, HDF was administered daily in diet to induce diabetes. A high and low dose of garlic oil and leek powder were given orally daily to HDF-diabetic rats. Compared to rats in the diabetic groups, the garlic oil and leek powder reduced serum cholesterol, triacylglycerol, low-density lipoprotein-cholesterol (LDL-c) and very low density lipoprotein-cholesterol (VLDL-c) levels. The garlic oil and leek powder also helped reduce hepatic destruction. A reduction was found in the gene expression in the hepatic homogenate of activating transcription factor 6 (ATF6) and X-Box Binding Protein1 (XBP1), Binding immunoglobulin protein (BIP), C/EBP homologous protein (CHOP), Jun N-terminal kinase (JNK), and peroxisome proliferator- activated receptor gamma (PPAR-γ). On the other hand, there was a significant upregulation in the mRNA expression of has been found in the promoter of glucose transporter 2 (Glut2), and miRNA 27a which is also a dose- and time-dependent manner. These results suggest that H2S donor as garlic oil and leek powder exhibits therapeutic potential for diabetes, which is most likely related to its protective effects against ER stress and regulating miRNA 27a and its target gene