Abstract 545: Cinnamon Extract Inhibit Lipids and Inflammation by Modulation of Transcription Factors: in vivo Model

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Zeynep Tuzcu ◽  
Cemal Orhan ◽  
Nurhan Sahin ◽  
Kazim Sahin ◽  
Vijaya Juturu
Keyword(s):  
Oxidative Stress ◽  
Transcription Factors ◽  
Fatty Acid ◽  
High Fat Diet ◽  
Fatty Acid Synthase ◽  
Liver Weight ◽  
Nuclear Factor ◽  
High Fat ◽  
Atp Citrate Lyase ◽  
Citrate Lyase

Objectives: CNM (CNM) polyphenol has antioxidant and anti-inflammatory properties. Therefore, we hypothesized CNM decrease heart disease risk factors and may enhance anti- inflammatory properties in rats fed a diet containing CNM. In this study, we evaluated the effects of CNM polyphenol on insulin resistance (IR), hyperlipidemia, hepatic transcription factors expressions [sterol regulatory element-binding protein1c (SREBP-1c), liver X receptor-α (LXR-α), nuclear factor kappa B p65 (NF-κB p65), nuclear factor-E2-related factor-2 (Nrf2)] in rats fed high fat diet (HFD). Method: Twenty-eight Wistar rats were allocated into four groups; (i) normal control; animals fed with normal chow (C ) (ii) CNM (C+CNM 100 mg/kg b.wt.), (iii) HFD (42% of calories as fat, high fat diet [HFD]), and (iv) HFD + CNM for 12 weeks. Blood analysis for triglycerides (TG) and cholesterol (CHOL), glucose, insulin, malonaldehyde (MDA a marker of oxidative stress [OS]) were estimated. Body weight, visceral fat and liver weight recorded and liver MDA assessed. SREBP-1c, LXR-α, ATP-citrate lyase (ACLY), fatty acid synthase (FAS), NF-κB p65 expressions and decreased the PPAR-α, p-IRS-1, Nrf2, HO-1 proteins were evaluated by Western blotting. Results: HFD rats of the liver had increased SREBP-1c, LXR-α, ATP-citrate lyase (ACLY), fatty acid synthase (FAS), NF-κB p65 expressions and decreased the PPAR-α, p-IRS-1, Nrf2, HO-1 expressions compared to control group. CNM supplementation decreased body weight (8.4%), visceral fat (36.6%), liver weight (17.7%), serum glucose and insulin concentrations, lipid profile ( P < 0.05), and serum and liver MDA (23.3% and 25.4 %) concentration compared to HFD rats ( P < 0.05). CNM decreased hepatic SREBP-1c (18.1 %), LXRα (27.9%), ATP-citrate lyase (ACLY, 22.7 %), fatty acid synthase (FAS, 15.8 %), NF-κB p65 (23.3%) and enhanced the PPAR-α, IRS-1 (72.7 %), Nrf2 (111.7 %) and HO-1 (72.1 %) proteins in HFD rat livers ( P < 0.05). Discussion: These results suggest CNM supplementation reduces hyperlipidemia, inflammation, and oxidative stress through activating transcription factors (SREBP-1c, LXR-α, NF-κB, and Nrf2) and anti-oxidative defense signaling pathway.

scholarly journals Cinnamon Polyphenol Extract Inhibits Hyperlipidemia and Inflammation by Modulation of Transcription Factors in High-Fat Diet-Fed Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Zeynep Tuzcu ◽  
Cemal Orhan ◽  
Nurhan Sahin ◽  
Vijaya Juturu ◽  
Kazim Sahin
Keyword(s):  
Oxidative Stress ◽  
Transcription Factors ◽  
Lipid Profile ◽  
High Fat Diet ◽  
Elevated Serum ◽  
Liver Weight ◽  
Serum Glucose ◽  
High Fat ◽  
Normal Chow ◽  
And Oxidative Stress

We evaluated the effects of cinnamon polyphenol extract on hepatic transcription factors expressions including SREBP-1c and LXR-α in rats fed high fat diet (HFD). Twenty-eight Wistar rats were allocated into four groups: (i) normal control: animals fed with normal chow; (ii) cinnamon: animals supplemented with cinnamon polyphenol; (iii) HFD: animals fed a high-fat diet; and (iv) HFD + cinnamon: animals fed a high-fat diet and treated with cinnamon polyphenol. Obesity was linked to hyperglycemia, hyperlipidemia, and oxidative stress as imitated by elevated serum glucose, lipid profile, and serum and liver malondialdehyde (MDA) concentrations. Cinnamon polyphenol decreased body weight, visceral fat, liver weight and serum glucose and insulin concentrations, liver antioxidant enzymes, and lipid profile (P<0.05) and reduced serum and liver MDA concentration compared to HFD rats (P<0.05). Cinnamon polyphenol also suppressed the hepatic SREBP-1c, LXR-α, ACLY, FAS, and NF-κB p65 expressions and enhanced the PPAR-α, IRS-1, Nrf2, and HO-1 expressions in the HFD rat livers (P<0.05). In conclusion, cinnamon polyphenol reduces the hyperlipidemia, inflammation, and oxidative stress through activating transcription factors and antioxidative defense signaling pathway in HFD rat liver.

Dillenia indica fruit extract suppressed diet-induced obesity in rat by down-regulating the mRNA level of proadipogenic transcription factors and lipid metabolizing enzymes

2020 ◽  
Vol 16 ◽  
Author(s):  
Syed A. Kuddus ◽  
Zarin Tasnim ◽  
Md. Hasanuzzaman Shohag ◽  
Tahmina Yasmin ◽  
Md. Sahab Uddin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transcription Factors ◽  
High Fat Diet ◽  
Mrna Level ◽  
Liver Weight ◽  
High Fat ◽  
Fruit Extract ◽  
Metabolizing Enzymes ◽  
Lipid Metabolizing Enzymes ◽  
Dillenia Indica

Background: Dillenia indica (Family: Dilleniaceae) is an antioxidant-rich edible fruit-bearing medicinal plant. The fruit of this plant (known as elephant apple) has many uses in traditional medicine. Objective: By considering its antioxidant content and ameliorating effects this study was aimed to evaluate the antiadipogenic effects of D. indica fruit extract (DIFE) in high-fat diet (HFD) fed obese rats. Methods: Male Wistar rats were fed with a standard diet (SD), or high-fat diet (HFD), or HFD with 100 mg/kg or 200 mg/kg or 400 mg/kg DIFE for 8 weeks. The fruit extract was given orally by feeding gavage. The body weight, liver weight, visceral fat weight, plasma lipids, and oxidative stress-related parameters were measured. The mRNA level of different adipogenesis related transcription factors, lipogenic and lipolytic enzymes was also evaluated. Results: Consumption of DIFE daily (400 mg/kg) for 8 weeks resulted in a significant reduction of high-fat diet-induced body weight, liver weight, visceral fat weight, total cholesterol, and LDL-cholesterol level. High-fat diet-mediated elevation of oxidative stress markers was also lowered, with a parallel augmentation of the activities of antioxidant enzymes, due to 400 mg/kg DIFE feeding. DIFE also down-regulated the mRNA level of important pro-adipogenic factors like PPARγ, LXRα, and SREBP1c which consequently down-regulated the transcript levels of lipogenic enzymes: ACC, FAS, HMHCR, and DGAT. The transcript level of lipolytic enzyme, HSL was also down-regulated in 400 mg/kg DIFE-fed rats. Conclusion: These findings indicate that the antioxidant-rich ethanolic extract of D. indica fruit can down-regulate the gene expression of pro-adipogenic transcription factors and lipid metabolizing enzymes and thus can suppress dietinduced obesity in Wistar rat.

scholarly journals Antioxidant-rich Tamarindus indica L. leaf extract reduced high-fat diet-induced obesity in rat through modulation of gene expression

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Syed Abdul Kuddus ◽  
Mazharul Islam Bhuiyan ◽  
Nusrat Subhan ◽  
Md Hasanuzzaman Shohag ◽  
Aura Rahman ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Transcription Factors ◽  
High Fat Diet ◽  
Wistar Rats ◽  
Liver Weight ◽  
Lipolytic Enzyme ◽  
Tamarindus Indica ◽  
Lipogenic Enzymes ◽  
High Fat

Abstract Background Different parts of the medicinal plant Tamarindus indica L. are full of phytochemicals that are able to reduce elevated blood pressure, blood sugar and lipids. These pharmacological effects are due to the presence of antioxidant type compounds in those parts of the plant. This study was aimed to explore the molecular mechanism of anti-obesity effects of ethanolic extract of T. indica L. leaves (TILE) through the evaluation of biochemical parameters and gene expression analysis in high-fat diet (HFD) consuming Wistar rats. Methods Male Wistar rats were supplied with a standard diet (SD), or HFD, or HFD with 100 mg/kg or 200 mg/kg or 400 mg/kg TILE for 8 weeks. The body weight, liver weight, fat weight, plasma lipids, and oxidative stress-related parameters were measured. The transcript levels of different adipogenesis related transcription factors, lipogenic enzymes, and lipolytic enzymes were also evaluated by quantitative real-time PCR. Result Phytochemical analysis demonstrated that TILE is enriched with a substantial level of polyphenols (287.20 ± 9.21 mg GAE/g extract) and flavonoids (107.52 ± 11.12 mg QE/g extract) which might be the reason of significant antioxidant and radical scavenging activities. Feeding of TILE (400 mg/kg/day) to HFD-fed rats increased activity of superoxide dismutase and catalase which is reflected as a significant reduction of oxidative stress markers like nitric oxide and malondialdehyde. TILE (400 mg/kg/day) feeding also down-regulated the mRNA levels of proadipogenic transcription factors including liver X receptor alpha (LXRα), peroxisome proliferator-activated receptor gamma (PPARγ), and sterol regulatory element-binding protein 1c (SREBP1c) in diet-induced obese rats. As a consequence of this, the mRNA level of lipogenic enzymes like acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), diacylglycerol acyltransferase (DGAT), and HMG-CoA reductase was down-regulated with a parallel up-regulation of the transcript level of lipolytic enzyme, hormone-sensitive lipase (HSL). Conclusion Observations from this study indicate that antioxidant-rich TILE can reduce HFD-induced body weight, fat weight and liver weight as well as blood lipids through down-regulating the gene expression of proadipogenic transcription factors and lipogenic enzymes with a concerted diminution of the gene expression of lipolytic enzyme, HSL.

Ezetimibe prevents hepatic steatosis induced by a high-fat but not a high-fructose diet

2013 ◽  
Vol 305 (2) ◽  
pp. E293-E304 ◽  
Author(s):  
Masateru Ushio ◽  
Yoshihiko Nishio ◽  
Osamu Sekine ◽  
Yoshio Nagai ◽  
Yasuhiro Maeno ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Liver Disease ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Fatty Acid Synthase ◽  
Binding Protein ◽  
High Fat ◽  
High Fructose Diet ◽  
High Fructose ◽  
Element Binding Protein

Nonalcoholic fatty liver disease is the most frequent liver disease. Ezetimibe, an inhibitor of intestinal cholesterol absorption, has been reported to ameliorate hepatic steatosis in human and animal models. To explore how ezetimibe reduces hepatic steatosis, we investigated the effects of ezetimibe on the expression of lipogenic enzymes and intestinal lipid metabolism in mice fed a high-fat or a high-fructose diet. CBA/JN mice were fed a high-fat diet or a high-fructose diet for 8 wk with or without ezetimibe. High-fat diet induced hepatic steatosis accompanied by hyperinsulinemia. Treatment with ezetimibe reduced hepatic steatosis, insulin levels, and glucose production from pyruvate in mice fed the high-fat diet, suggesting a reduction of insulin resistance in the liver. In the intestinal analysis, ezetimibe reduced the expression of fatty acid transfer protein-4 and apoB-48 in mice fed the high-fat diet. However, treatment with ezetimibe did not prevent hepatic steatosis, hyperinsulinemia, and intestinal apoB-48 expression in mice fed the high-fructose diet. Ezetimibe decreased liver X receptor-α binding to the sterol regulatory element-binding protein-1c promoter but not expression of carbohydrate response element-binding protein and fatty acid synthase in mice fed the high-fructose diet, suggesting that ezetimibe did not reduce hepatic lipogenesis induced by the high-fructose diet. Elevation of hepatic and intestinal lipogenesis in mice fed a high-fructose diet may partly explain the differences in the effect of ezetimibe.

scholarly journals Red Kidney Beans Ameliorate the High Fat Diet-Induced Hepatic Fat Accumulation and Inflammation

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 778-778
Author(s):  
Ibtesam Sleem ◽  
Ashley Toney ◽  
QinYin Shi ◽  
Soonkyu Chung ◽  
Vicki Schlegel
Keyword(s):  
High Fat Diet ◽  
Fatty Acid Synthase ◽  
Liver Weight ◽  
Low Grade ◽  
High Fat ◽  
Gene Expressions ◽  
Fat Accumulation ◽  
Kidney Beans ◽  
Hepatic Fat ◽  
Red Kidney Beans

Abstract Objectives High fat diet (HFD)-induced obesity links with prevalence of metabolic dysfunction, including low-grade chronic inflammation, insulin resistance, and hepatic steatosis. Dry edible beans (DEBs) play a significant role in human nutrition as a rich source of proteins, carbohydrates, fibers, and various micronutrients. The aim of this study is to evaluate the ability of red kidney beans (RKBs) to attenuate the deleterious effects of HFD in the liver. Methods Syrian hamsters were randomly assigned with one of five experimental diet groups; low fat diet (control), high fat diet, high fat diet with 5% whole beans (HFD + B), high fat diet with 4.5% dehulled beans (HFD + DHB) and high fat diet with 0.5% hull of beans (HFD + HB) and fed for 4 weeks. Results Supplementation of RKB resulted in lower body weight, liver weight, and glucose levels (P &lt; 0.001) in HFD + B and HFD + DHB group compared to HFD group. Adding RKBs downregulated gene expressions related to inflammation (e.g., interleukin 6 (IL-6)) and lipogenesis (e.g., hepatic fatty acid synthase (FASN)) in the liver. Furthermore, RKBs supplemented groups showed reduced hepatic fat accumulation in comparison with the HFD group. Conclusions Supplementation of RKBs and their hulls attenuates hepatic stresses by decreasing the lipogenesis and inflammation, which contribute to enhancing insulin sensitivity. Funding Sources USDA Multi-Hatch, Program: W-3150.

Aromatic aldehyde compound cuminaldehyde protects nonalcoholic fatty liver disease in rats feeding high fat diet

2019 ◽  
Vol 38 (7) ◽  
pp. 823-832 ◽  
Author(s):  
MR Haque ◽  
SH Ansari
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Fatty Liver ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
Liver Enzymes ◽  
Liver Weight ◽  
High Fat ◽  
Nonalcoholic Fatty Liver ◽  
And Oxidative Stress

Nonalcoholic fatty liver disease (NAFLD) is caused by fat accumulation and is related with obesity and oxidative stress. In this study, we investigated the effect of cuminaldehyde on NAFLD in rats fed a high fat diet (HFD). Male Wistar rats were fed a HFD for 42 days to induce NAFLD. The progression of NAFLD was evaluated by histology and measuring liver enzymes (alanine transaminase and aspartate transaminase), serum and hepatic lipids (total triglycerides and total cholesterol), and oxidative stress markers (thiobarbituric acid reactive substances, glutathione, superoxide dismutase, and catalase). The HFD feeding increased the liver weight and caused NAFLD, liver steatosis, hyperlipidemia, oxidative stress, and elevated liver enzymes. Administration of cuminaldehyde ameliorated the changes in hepatic morphology and liver weight, decreased levels of liver enzymes, and inhibited lipogenesis. Our findings suggest that cuminaldehyde could improve HFD-induced NAFLD via abolishment of hepatic oxidative damage and hyperlipidemia. Cuminaldehyde might be considered as a potential aromatic compound in the treatment of NAFLD and obesity through the modulation of lipid metabolism.

scholarly journals Fisetin Protects Against Hepatic Steatosis Through Regulation of the Sirt1/AMPK and Fatty Acid β-Oxidation Signaling Pathway in High-Fat Diet-Induced Obese Mice

2018 ◽  
Vol 49 (5) ◽  
pp. 1870-1884 ◽  
Author(s):  
Chian-Jiun Liou ◽  
Ciao-Han Wei ◽  
Ya-Ling Chen ◽  
Ching-Yi Cheng ◽  
Chia-Ling Wang ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Hepatic Steatosis ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Fatty Acid Synthase ◽  
Epididymal Adipose Tissue ◽  
Obese Mice ◽  
High Fat

Background/Aims: Fisetin is a naturally abundant flavonoid isolated from various fruits and vegetables that was recently identified to have potential biological functions in improving allergic airway inflammation, as well as anti-oxidative and anti-tumor properties. Fisetin has also been demonstrated to have anti-obesity properties in mice. However, the effect of fisetin on nonalcoholic fatty liver disease (NAFLD) is still elusive. Thus, the present study evaluated whether fisetin improves hepatic steatosis in high-fat diet (HFD)-induced obese mice and regulates lipid metabolism of FL83B hepatocytes in vitro. Methods: NAFLD was induced by HFD in male C57BL/6 mice. The mice were then injected intraperitoneally with fisetin for 10 weeks. In another experiment, FL83B cells were challenged with oleic acid to induce lipid accumulation and treated with various concentrations of fisetin. Results: NAFLD mice treated with fisetin had decreased body weight and epididymal adipose tissue weight compared to NAFLD mice. Fisetin treatment also reduced liver lipid droplet and hepatocyte steatosis, alleviated serum free fatty acid, and leptin concentrations, significantly decreased fatty acid synthase, and significantly increased phosphorylation of AMPKα and the production of sirt-1 and carnitine palmitoyltransferase I in the liver tissue. In vitro, fisetin decreased lipid accumulation and increased lipolysis and β-oxidation in hepatocytes. Conclusion: This study suggests that fisetin is a potential novel treatment for alleviating hepatic lipid metabolism and improving NAFLD in mice via activation of the sirt1/AMPK and β-oxidation pathway.

scholarly journals RNA-seq reveals novel mechanistic targets of withaferin A in prostate cancer cells

2020 ◽  
Vol 41 (6) ◽  
pp. 778-789 ◽  
Author(s):  
Su-Hyeong Kim ◽  
Eun-Ryeong Hahm ◽  
Krishna B Singh ◽  
Sruti Shiva ◽  
Jacob Stewart-Ornstein ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Acid Synthesis ◽  
Acetyl Coa Carboxylase ◽  
Rna Seq ◽  
Atp Citrate Lyase ◽  
Acetyl Coa ◽  
Citrate Lyase

Abstract Withaferin A (WA) is a promising phytochemical exhibiting in vitro and in vivo anticancer activities against prostate and other cancers, but the mechanism of its action is not fully understood. In this study, we performed RNA-seq analysis using 22Rv1 human prostate cancer cell line to identify mechanistic targets of WA. Kyoto Encyclopedia of Genes and Genomes pathway analysis of the differentially expressed genes showed most significant enrichment of genes associated with metabolism. These results were validated using LNCaP and 22Rv1 human prostate cancer cells and Hi-Myc transgenic mice as models. The intracellular levels of acetyl-CoA, total free fatty acids and neutral lipids were decreased significantly following WA treatment in both cells, which was accompanied by downregulation of mRNA (confirmed by quantitative reverse transcription-polymerase chain reaction) and protein levels of key fatty acid synthesis enzymes, including ATP citrate lyase, acetyl-CoA carboxylase 1, fatty acid synthase and carnitine palmitoyltransferase 1A. Ectopic expression of c-Myc, but not constitutively active Akt, conferred a marked protection against WA-mediated suppression of acetyl-CoA carboxylase 1 and fatty acid synthase protein expression, and clonogenic cell survival. WA was a superior inhibitor of cell proliferation and fatty acid synthesis in comparison with known modulators of fatty acid metabolism including cerulenin and etomoxir. Intraperitoneal WA administration to Hi-Myc transgenic mice (0.1 mg/mouse, three times/week for 5 weeks) also resulted in a significant decrease in circulating levels of total free fatty acids and phospholipids, and expression of ATP citrate lyase, acetyl-CoA carboxylase 1, fatty acid synthase and carnitine palmitoyltransferase 1A proteins in the prostate in vivo.

scholarly journals Normal Flux through ATP-Citrate Lyase or Fatty Acid Synthase Is Not Required for Glucose-stimulated Insulin Secretion

2007 ◽  
Vol 282 (43) ◽  
pp. 31592-31600 ◽  
Author(s):  
Jamie W. Joseph ◽  
Matthew L. Odegaard ◽  
Sarah M. Ronnebaum ◽  
Shawn C. Burgess ◽  
Jeffrey Muehlbauer ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Atp Citrate Lyase ◽  
Citrate Lyase ◽  
Glucose Stimulated Insulin Secretion
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