scholarly journals Metabolomic profiling reveals effects of marein on energy metabolism in HepG2 cells

2017 ◽  
Author(s):  
Baoping Jiang ◽  
Liang Le ◽  
Keping Hu ◽  
Lijia Xu ◽  
Peigen Xiao
Keyword(s):  
Insulin Resistance ◽  
Ethyl Acetate ◽  
High Glucose ◽  
High Fat Diet ◽  
Hepg2 Cells ◽  
Ethyl Acetate Extract ◽  
Glycogen Synthesis ◽  
High Fat ◽  
Protein Levels ◽  
Coreopsis Tinctoria

AbstractPrevious studies have suggested thatCoreopsis tinctoriaimproves insulin resistance in rats fed with high-fat diet. But little is known about the antidiabetic effects of marein which is the main component ofC. tinctoria. This study investigated the effects of ethyl acetate extract ofC. tinctoria(AC) on insulin resistance (IR) in rats fed a high-fat diet. High glucose and fat conditions cause a significant increase in blood glucose, insulin, serum TC,TG and LDL-C, leading to an abnormal IR in rats. However, treatment with AC protects against HFD-induced IR by improving fasting serum glucose and lipid homeostasis. High glucose conditions cause a significant decrease in glycogen synthesis and increases PEPCK and G6Pase protein levels and Krebs-cycle-related enzymes levels, leading to an abnormal metabolic state in HepG2 Cells. However, treatment with Marein improves IR by increasing glucose uptake and glycogen synthesis and by downregulating PEPCK and G6Pase protein levels. The statistical analysis of HPLC/MS data demonstrates that Marein restores the normal metabolic state. The results show that AC ameliorates IR in rats and Marein has the potential effect in improving IR by ameliorating glucose metabolic disorders.AbbreviationsACethyl acetate extract ofCoreopsis tinctoriaTCATricarboxylic acidHepG2hepatocellular carcinoma cell line2-NBDG2-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)-2-deoxyglucoseG6Paseglucose-6-phosphatasePEPCKphosphoenolpyruvate carboxykinaseIRinsulin resistanceHFDhigh-fat dietSDHAsuccinate dehydrogenase flavoprotein subunitACO2aconitase 2IDH2isocitrate dehydrogenase 2CScitrate synthaseFHfumarate hydrataseMDH2malate dehydrogenaseDLSTdihydrolipoamide S-succinyltransferase

scholarly journals The Ethyl Acetate Extract of Leaves of Ugni molinae Turcz. Improves Neuropathological Hallmarks of Alzheimer’s Disease in Female APPswe/PS1dE9 Mice Fed with a High Fat Diet

2018 ◽  
Vol 66 (3) ◽  
pp. 1175-1191 ◽  
Author(s):  
Daniela Jara-Moreno ◽  
Rubn D. Castro-Torres ◽  
Miren Ettcheto ◽  
Carme Auladell ◽  
Marcelo J. Kogan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Ethyl Acetate ◽  
High Fat Diet ◽  
Ethyl Acetate Extract ◽  
High Fat ◽  
Ugni Molinae

scholarly journals Resveratrol Ameliorates High-Fat-Diet-Induced Abnormalities in Hepatic Glucose Metabolism in Mice via the AMP-Activated Protein Kinase Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Caiping Lu ◽  
Hanying Xing ◽  
Linquan Yang ◽  
Kaiting Chen ◽  
Linyi Shu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Protein Kinase ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
High Fat Diet ◽  
Blood Glucose Concentration ◽  
Glycogen Synthesis ◽  
Liver Fat ◽  
High Fat ◽  
Amp Activated Protein Kinase

Diabetes mellitus is highly prevalent worldwide. High-fat-diet (HFD) consumption can lead to liver fat accumulation, impair hepatic glycometabolism, and cause insulin resistance and the development of diabetes. Resveratrol has been shown to improve the blood glucose concentration of diabetic mice, but its effect on the abnormal hepatic glycometabolism induced by HFD-feeding and the mechanism involved are unknown. In this study, we determined the effects of resveratrol on the insulin resistance of high-fat-diet-fed mice and a hepatocyte model by measuring serum biochemical indexes, key indicators of glycometabolism, glucose uptake, and glycogen synthesis in hepatocytes. We found that resveratrol treatment significantly ameliorated the HFD-induced abnormalities in glucose metabolism in mice, increased glucose absorption and glycogen synthesis, downregulated protein phosphatase 2A (PP2A) and activated Ca2+/CaM-dependent protein kinase kinase β (CaMKKβ), and increased the phosphorylation of AMP-activated protein kinase (AMPK). In insulin-resistant HepG2 cells, the administration of a PP2A activator or CaMKKβ inhibitor attenuated the effects of resveratrol, but the administration of an AMPK inhibitor abolished the effects of resveratrol. Resveratrol significantly ameliorates abnormalities in glycometabolism induced by HFD-feeding and increases glucose uptake and glycogen synthesis in hepatocytes. These effects are mediated through the activation of AMPK by PP2A and CaMKKβ.

scholarly journals Extracts ofCoreopsis tinctoriaNutt. Flower Exhibit Antidiabetic Effects via the Inhibition ofα-Glucosidase Activity

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Wujie Cai ◽  
Lijing Yu ◽  
Yu Zhang ◽  
Li Feng ◽  
Siyuan Kong ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
High Fat Diet ◽  
Fasting Blood Glucose ◽  
Antioxidant Properties ◽  
Serum Triglyceride ◽  
Chow Diet ◽  
High Fat ◽  
Glucosidase Activity ◽  
Coreopsis Tinctoria

The aim of this study was to assay the effects ofCoreopsis tinctoriaNutt. flower extracts on hyperglycemia of diet-induced obese mice and the underlying mechanisms.Coreopsis tinctoriaflower was extracted with ethanol and water, respectively. The total phenol, flavonoid levels, and the constituents of the extracts were measured. For the animal experiments, C57BL/6 mice were fed with a chow diet, high-fat diet, or high-fat diet mixed with 0.4% (w/w) water and ethanol extracts ofCoreopsis tinctoriaflower for 8 weeks. The inhibitory effects of the extracts onα-glucosidase activity and the antioxidant properties were assayedin vitro. We found that the extracts blocked the increase of fasting blood glucose, serum triglyceride (TG), insulin, leptin, and liver lipid levels and prevented the development of glucose tolerance impairment and insulin resistance in the C57BL/6 mice induced by a high-fat diet. The extracts inhibitedα-glycosidase activity and increased oxidant activityin vitro. In conclusion,Coreopsis tinctoriaflower extracts may ameliorate high-fat diet-induced hyperglycemia and insulin resistance. The underling mechanism may be via the inhibition ofα-glucosidase activity. Our data indicate thatCoreopsis tinctoriaflower could be used as a beverage supplement and a potential source of drugs for treatment of diabetics.

miR-182-5p Attenuates High-Fat -Diet-Induced Nonalcoholic Steatohepatitis in Mice

2018 ◽  
Vol 17 (5) ◽  
pp. 0-10
Author(s):  
Qionghe Liang ◽  
Huan Chen ◽  
Xiaoqun Xu ◽  
Weiwei Jiang
Keyword(s):  
Nonalcoholic Steatohepatitis ◽  
High Fat Diet ◽  
Hepg2 Cells ◽  
Treated Group ◽  
High Fat ◽  
Protein Levels ◽  
Tlr4 Mrna ◽  
Increased Risk

Introduction and Aim: Patients with NASH have increased risk for sepsis or cardiovascular disease after Liver transplantation. An important role of Toll-like receptor (TLR) 4 in the pathogenesis of nonalcoholic steatohepatitis (NASH) was demonstrated. Here, we study the role of miR-182-5p in TLR4 expression and high-fat-diet (HFD)-induced NASH in vitro and in vivo. Methods: Following transfection with a miR-182-5p mimic, the effect of miR-182-5p on TLR4 in RAW264.7 and HepG2 cells was investigated. Following administration of the miR-182-5p mimic into the livers of HFD-induced NASH mice, we determined the in vivo expression of TLR4, TNFα, and IL-6 and assessed the histologic features of the livers. Results: Following lipopolysaccharide (LPS) treatment of RAW264.7 cells, real-time RT-PCR and western blot results indicated decreases levels of TLR4 mRNA and protein in the miR-182-5p group as compared with levels observed in controls, with similar trends were observed in TNFα and IL-6 protein levels. Following oleic acid (OA) treatment of HepG2 cells, TLR4, TNFα, and IL-6 levels were significantly decreased in the miR-182-5p group as compared with levels observed in controls. Following miR-182-5p administration, TLR4 mRNA and protein levels decreased along with those of TNFα and IL-6 proteins, and the liver weight/body weight ratio of treated mice was less than that observed in controls. Furthermore, hematoxylin and eosin staining showed that the miR-182-5p-treated group exhibited low adipose-cell cross-sectional areas, and Oil Red O staining showed decreases in the size of lipid droplets in the miR-182-5p-treated group. Conclusions: miR-182-5p ameliorated HFD-induced NASH by suppressing TLR4.

scholarly journals Glycerol-3-phosphate acyltransferase-4-deficient mice are protected from diet-induced insulin resistance by the enhanced association of mTOR and rictor

2014 ◽  
Vol 307 (3) ◽  
pp. E305-E315 ◽  
Author(s):  
Chongben Zhang ◽  
Daniel E. Cooper ◽  
Trisha J. Grevengoed ◽  
Lei O. Li ◽  
Eric L. Klett ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
High Fat Diet ◽  
Glycogen Synthesis ◽  
Mammalian Target Of Rapamycin ◽  
Hepatic Insulin Resistance ◽  
High Fat ◽  
Lipid Signal ◽  
Mouse Hepatocytes ◽  
Triacylglycerol Accumulation ◽  
Deficient Mice

Glycerol-3-phosphate acyltransferase (GPAT) activity is highly induced in obese individuals with insulin resistance, suggesting a correlation between GPAT function, triacylglycerol accumulation, and insulin resistance. We asked whether microsomal GPAT4, an isoform regulated by insulin, might contribute to the development of hepatic insulin resistance. Compared with control mice fed a high fat diet, Gpat4 −/− mice were more glucose tolerant and were protected from insulin resistance. Overexpression of GPAT4 in mouse hepatocytes impaired insulin-suppressed gluconeogenesis and insulin-stimulated glycogen synthesis. Impaired glucose homeostasis was coupled to inhibited insulin-stimulated phosphorylation of Akt(Ser473) and Akt(Thr308). GPAT4 overexpression inhibited rictor's association with the mammalian target of rapamycin (mTOR), and mTOR complex 2 (mTORC2) activity. Compared with overexpressed GPAT3 in mouse hepatocytes, GPAT4 overexpression increased phosphatidic acid (PA), especially di16:0-PA. Conversely, in Gpat4 −/− hepatocytes, both mTOR/rictor association and mTORC2 activity increased, and the content of PA in Gpat4 −/− hepatocytes was lower than in controls, with the greatest decrease in 16:0-PA species. Compared with controls, liver and skeletal muscle from Gpat4 −/−-deficient mice fed a high-fat diet were more insulin sensitive and had a lower hepatic content of di16:0-PA. Taken together, these data demonstrate that a GPAT4-derived lipid signal, likely di16:0-PA, impairs insulin signaling in mouse liver and contributes to hepatic insulin resistance.

scholarly journals Impaired ferritinophagy induced hepatic insulin resistance via endoplasmic reticulum stress of high fat diet mice

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Chunjie Jiang ◽  
Shanshan Zhang ◽  
Hongmei Zeng ◽  
Jingjing Liu ◽  
Dan Li ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Glucose Uptake ◽  
Iron Metabolism ◽  
High Fat Diet ◽  
Hepg2 Cells ◽  
Ammonium Citrate ◽  
Iron Level ◽  
High Fat

AbstractEmerging evidence has been revealed that high fat diet (HFD) correlate with insulin resistance (IR) which could be induced by endoplasmic reticulum stress (ERS). Recently, obesity or HFD induced nonalcoholic fatty liver disease (NAFLD) could promote alteration of iron metabolism. Disorder of iron metabolism have been linked to unnormal metabolism of glucose and lipid. Herein, we investigated the effect of impaired iron homeostasis on hepatic IR, focusing on ferritinophagy. Male C57/6J mice were administered with HFD (60% energy from fat) or LFD (10% energy from fat) for 10 weeks (n = 10), and Palmitic acid (PA)-insulin treated HepG2 cells were also established. Hepatic IR as evidenced by increased hepatic steatosis and decreased of p-AKT (48%, p < 0.0005), p-GSK-3β (34%, p < 0.05) in the liver of HFD mice. In addition, decreased iron level and expression NCOA4, as well as increased up-regulation of IRE1α and EIF2α were observed in HFD liver. By using desferrioxamine (DFO) and ferric ammonium citrate (FAC), we examined iron level on IRE1α and EIF2α. And glucose uptake assay shown that FAC supplementation, and ERS inhibitors of 4-PBA and STF could improve the glucose uptake of HepG2 cells in the presence of PA. Furthermore, we evaluated the glucose uptake of HepG2 cells incubated with adenovirus which mediated overexpression of NCOA4, FAC, 4-PBA (ERS inhibitor) or STF (IRE1 inhibitor). Taken together, deficiency of iron induced by impaired ferritinophagy induced hepatic IR, partly by aggravating hepatic ERS, especially IRE1 signal pathway in vivo and vitro. These findings provide evidence and new insight for therapeutic strategy of iron deficiency in NAFLD.

scholarly journals NAC Supplementation of Hyperglycemic Rats Prevents the Development of Insulin Resistance and Improves Antioxidant Status but Only Alleviates General and Salivary Gland Oxidative Stress

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Anna Zalewska ◽  
Sara Zięba ◽  
Paula Kostecka-Sochoń ◽  
Agnieszka Kossakowska ◽  
Małgorzata Żendzian-Piotrowska ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Salivary Gland ◽  
High Fat Diet ◽  
Antioxidant Status ◽  
High Fat ◽  
Protein Levels ◽  
Saliva Secretion ◽  
Whole Saliva ◽  
Oxidative Modifications

Previous studies based on animal models demonstrated that N-acetylcysteine (NAC) prevents oxidative stress and improves salivary gland function when the NAC supplementation starts simultaneously with insulin resistance (IR) induction. This study is the first to evaluate the effect of a 4-week NAC supply on the antioxidant barrier and oxidative stress in Wistar rats after six weeks of high-fat diet (HFD) intake. Redox biomarkers were evaluated in the parotid (PG) and submandibular (SMG) salivary glands and stimulated whole saliva (SWS), as well as in the plasma and serum. We demonstrated that the activity of salivary peroxidase and superoxide dismutase and total antioxidant capacity were significantly higher in PG, SMG, and SWS of IR rats treated with NAC. It appears that in PG and SMG of rats fed an HFD, N-acetylcysteine supplementation abolishes oxidative modifications to proteins (evidenced by decreased content of advanced oxidation protein products (AOPP) and advanced glycation end products (AGE)). Simultaneously, it does not reverse oxidative modifications of lipids (as seen in increased concentration of 8-isoprostanes and 4-hydroxynonenal vs. the control), although it reduces the peroxidation of salivary lipids in relation to the group fed a high-fat diet alone. NAC administration increased protein levels in PG and SMG but did not affect saliva secretion, which was significantly lower compared to the controls. To sum up, the inclusion of NAC supplementation after six weeks of HFD feeding was effective in improving the general and salivary gland antioxidant status. Nevertheless, NAC did not eliminate salivary oxidative stress and only partially prevented salivary gland dysfunction.

scholarly journals Lactiplantibacillus plantarum MG4296 and Lacticaseibacillus paracasei MG5012 Ameliorates Insulin Resistance in Palmitic Acid-Induced HepG2 Cells and High Fat Diet-Induced Mice

2021 ◽  
Vol 9 (6) ◽  
pp. 1139
Author(s):  
GaYeong Won ◽  
Soo-Im Choi ◽  
Chang-Ho Kang ◽  
Gun-Hee Kim
Keyword(s):  
Insulin Resistance ◽  
Glucose Tolerance ◽  
Palmitic Acid ◽  
High Fat Diet ◽  
Hepg2 Cells ◽  
Glycogen Content ◽  
Histopathological Analysis ◽  
Model Assessment ◽  
High Fat

The purpose of this study was to evaluate the capacity of Lactiplantibacillus plantarum MG4296 (MG4296) and Lacticaseibacillus paracasei MG5012 (MG5012) on insulin resistance (IR) and diabetes-related metabolic changes in palmitic acid (PA)-induced HepG2 cells and high-fat diet-induced mice. In vitro, cell-free extracts of MG4296 and MG5012 alleviated IR by increasing glucose uptake and glycogen content in PA-induced insulin-resistant HepG2 cells. In vivo, MG4296 and MG5012 supplementation markedly decreased body weight and glucose tolerance. Administration of both strains also improved serum glucose, glycated hemoglobin, insulin, triglyceride, LDL/HDL ratio, and homeostatic model assessment of IR (HOMA-IR). Histopathological analysis of liver tissue demonstrated a significant reduction in lipid accumulation and glycogen content. Moreover, MG4296 and MG5012 treatment enhanced phosphoinositide-3 kinase (PI3K)/protein kinase B (Akt) expression in the liver. Overall, MG4296 and MG5012 could prevent HFD-induced glucose tolerance and hyperglycemia by improving IR. Therefore, L. plantarum MG4296 and L. paracasei MG5012 could be useful as new probiotics candidates to improve T2DM.

Sign in / Sign up

Export Citation Format

Share Document