scholarly journals Shugan Xiaozhi Decoction Attenuates Nonalcoholic Steatohepatitis by Enhancing PPARαand L-FABP Expressions in High-Fat-Fed Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Yu-feng Xing ◽  
Zhen Zhang ◽  
Wen-Jun Fu ◽  
Da-qiao Zhou ◽  
Ailsa Chui-ying Yuen ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Nonalcoholic Steatohepatitis ◽  
Chemical Constituents ◽  
Ionization Mass ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
High Fat ◽  
Peroxisome Proliferator Activated Receptor ◽  
Fatty Acid Binding ◽  
Dose Dependent

This study aimed to investigate the effects of Shugan Xiaozhi decoction (SX) on nonalcoholic steatohepatitis (NASH) induced by high-fat diet in rats. The rats were randomly divided into 6 groups, namely, control, model, fenofibrate, and three different dosage of SX (10, 20, and 40 g/kg/day, p.o.). After establishing the NASH model, at 8 weeks of the experiment, treatments were administrated intragastrically to the fenofibrate and SX groups. All rats were killed after 4 weeks of treatment. Compared with the model group, alanine aminotransferase (ALT), aspartate aminotransferase (AST), free fatty acid (FFA), total cholesterol (TC), triacylglycerol (TG), and low-density lipoprotein cholesterol (LDL) serum in the serum were significantly reduced in all SX treatment groups in a dose-dependent manner. Evidence showed that SX could protect the liver by upregulating the gene and protein expressions of peroxisome proliferator-activated receptor alpha (PPARα) and liver fatty acid binding protein (L-FABP) in a dose-dependent manner. Chemical constituents of SX were further analyzed by ultraperformance liquid chromatography coupled with electrospray ionization mass spectrometry (UPLC-ESI-MS) and 30 chemicals in the ethanolic extract were tentatively identified. To conclude, our results clearly indicated that SX could protect liver functions and relieve hepatic steatosis and inflammation.

scholarly journals Genistin: A Novel Potent Anti-Adipogenic and Anti-Lipogenic Agent

Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2042 ◽  
Author(s):  
Yae Rim Choi ◽  
Jaewon Shim ◽  
Min Jung Kim
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Binding Protein ◽  
Regulatory Element ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Atp Citrate Lyase ◽  
Peroxisome Proliferator Activated Receptor ◽  
Fatty Acid Binding ◽  
Specific Proteins

Soy isoflavones are popular ingredients with anti-adipogenic and anti-lipogenic properties. The anti-adipogenic and anti-lipogenic properties of genistein are well-known, but those of genistin and glycitein remain unknown, and those of daidzein are characterized by contrasting data. Therefore, the purpose of our study was to investigate the effects of daidzein, glycitein, genistein, and genistin on adipogenesis and lipogenesis in 3T3-L1 cells. Proliferation of 3T3-L1 preadipocytes was unaffected by genistin and glycitein, but it was affected by 50 and 100 µM genistein and 100 µM daidzein for 48 h. Among the four isoflavones, only 50 and 100 µM genistin and genistein markedly suppressed lipid accumulation during adipogenesis in 3T3-L1 cells through a similar signaling pathway in a dose-dependent manner. Genistin and genistein suppress adipocyte-specific proteins and genes, such as peroxisome proliferator-activated receptor γ (PPARγ), CCAAT-enhancer-binding protein α (C/EBPα), and adipocyte binding protein 2 (aP2)/fatty acid-binding protein 4 (FABP4), and lipogenic enzymes such as ATP citrate lyase (ACL), acetyl-CoA carboxylase 1 (ACC1), and fatty acid synthase (FAS). Both isoflavones also activate AMP-activated protein kinase α (AMPKα), an essential factor in adipocyte differentiation, and inhibited sterol regulatory element-binding transcription factor 1c (SREBP-1c). These results indicate that genistin is a potent anti-adipogenic and anti-lipogenic agent.

scholarly journals Lactobacillus plantarumLG42 Isolated from Gajami Sik-Hae Inhibits Adipogenesis in 3T3-L1 Adipocyte

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Jeong-Eun Park ◽  
Suk-Heung Oh ◽  
Youn-Soo Cha
Keyword(s):  
Transcription Factors ◽  
Fatty Acid ◽  
Lipid Accumulation ◽  
Binding Protein ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Peroxisome Proliferator Activated Receptor ◽  
Fatty Acid Binding ◽  
Intracellular Lipid Accumulation ◽  
Glycerol 3 Phosphate Dehydrogenase

We investigated whether lactic acid bacteria isolated from gajami sik-hae (GLAB) are capable of reducing the intracellular lipid accumulation by downregulating the expression of adipogenesis-related genes in differentiated 3T3-L1 cells. The GLAB,Lactobacillus plantarumLG42, significantly decreased the intracellular triglyceride storage and the glycerol-3-phosphate dehydrogenase (GPDH) activity in a dose-dependent manner. mRNA expression of transcription factors like peroxisome proliferator-activated receptor (PPAR)γand CCAAT/enhancer-binding protein (C/EBP)αinvolved in adipogenesis was markedly decreased by the GLAB treatment. Moreover, the GLAB also decreased the expression level of adipogenic markers like adipocyte fatty acid binding protein (aP2), leptin, GPDH, and fatty acid translocase (CD36) significantly. These results suggest that the GLAB inhibits lipid accumulation in the differentiated adipocyte through downregulating the expression of adipogenic transcription factors and other specific genes involved in lipid metabolism.

scholarly journals Peroxisome Proliferator-Activated Receptor α Mediates the Effects of High-Fat Diet on Hepatic Gene Expression

Endocrinology ◽  
2006 ◽  
Vol 147 (3) ◽  
pp. 1508-1516 ◽  
Author(s):  
David Patsouris ◽  
Janardan K. Reddy ◽  
Michael Müller ◽  
Sander Kersten
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Microarray Analysis ◽  
High Fat Diet ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Wild Type ◽  
High Fat ◽  
Fat Feeding

Peroxisome proliferator-activated receptors (PPARs) are transcription factors involved in the regulation of numerous metabolic processes. The PPARα isotype is abundant in liver and activated by fasting. However, it is not very clear what other nutritional conditions activate PPARα. To examine whether PPARα mediates the effects of chronic high-fat feeding, wild-type and PPARα null mice were fed a low-fat diet (LFD) or high-fat diet (HFD) for 26 wk. HFD and PPARα deletion independently increased liver triglycerides. Furthermore, in wild-type mice HFD was associated with a significant increase in hepatic PPARα mRNA and plasma free fatty acids, leading to a PPARα-dependent increase in expression of PPARα marker genes CYP4A10 and CYP4A14. Microarray analysis revealed that HFD increased hepatic expression of characteristic PPARα target genes involved in fatty acid oxidation in a PPARα-dependent manner, although to a lesser extent than fasting or Wy14643. Microarray analysis also indicated functional compensation for PPARα in PPARα null mice. Remarkably, in PPARα null mice on HFD, PPARγ mRNA was 20-fold elevated compared with wild-type mice fed a LFD, reaching expression levels of PPARα in normal mice. Adenoviral overexpression of PPARγ in liver indicated that PPARγ can up-regulate genes involved in lipo/adipogenesis but also characteristic PPARα targets involved in fatty acid oxidation. It is concluded that 1) PPARα and PPARα-signaling are activated in liver by chronic high-fat feeding; and 2) PPARγ may compensate for PPARα in PPARα null mice on HFD.

scholarly journals Regulation of cardiac fatty acids metabolism in transgenic mice overexpressing bovine GH

2009 ◽  
Vol 201 (3) ◽  
pp. 419-427 ◽  
Author(s):  
Fausto Bogazzi ◽  
Francesco Raggi ◽  
Federica Ultimieri ◽  
Dania Russo ◽  
Aldo D'Alessio ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Transgenic Mice ◽  
Fatty Acid Transport ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Fatty Acid Binding ◽  
Chain Acyl ◽  
Fatty Acids Metabolism ◽  
Key Enzyme ◽  
Key Steps

Cardiac energy metabolism depends mainly on fatty acid (FA) oxidation; however, regulation of FA metabolism in acromegalic (Acro) heart is unknown. The aim of the study was to evaluate cardiac expression of key proteins of FA metabolism in young and elder transgenic mice overexpressing bovine GH Acro. Expression of proteins regulating FA entry into the cells, their uptake by mitochondria and β-oxidation were evaluated by western blot, while FA content by Fourier transform infrared microspectrometry. Regulatory mechanisms of key steps of FA metabolism were also studied. The expression of plasma-membrane FA carriers (fatty acid-binding protein and fatty acid transport protein-1) and acylCoA synthetase was higher in young and lower in elder Acro than in corresponding controls; likewise, expression of cytoplasm to mitochondria-1 (CPT-1), the key enzyme of mitochondrial FA uptake, and that of medium-chain acyl-CoA dehydrogenase and long-chain acyl-CoA dehydrogenase, two regulatory β-oxidation dehydrogenases, followed a similar pattern. FA content was lower in young and higher in elder Acro than in wild-type, suggesting an increased utilisation in young animals. GH regulated expression of key proteins of FA metabolism through changes in peroxisome proliferator-activated receptor α (PPARα) expression, which varied accordingly. GH effect was confirmed by treatment of Acro mice with a receptor antagonist, which abolished changes in key proteins of FA metabolism in young Acro. GH increased phosphorylation of AMP-activated protein kinase and anti-acetyl-CoA-carboxylase, two regulatory kinases, leading to lower CPT-1 inhibition by malonyl-CoA, and intervened in regulating PPARα expression through the ERK 1/2 pathway. In conclusion, chronic GH excess increased FA metabolism in the young age, whereas its action was overwhelmed in elder ages likely by GH-independent mechanisms, leading to reduced expression of key enzyme of FA metabolism.

SUMO modification selectively regulates transcriptional activity of peroxisome-proliferator-activated receptor γ in C2C12 myotubes

2010 ◽  
Vol 433 (1) ◽  
pp. 155-161 ◽  
Author(s):  
Sung Soo Chung ◽  
Byung Yong Ahn ◽  
Min Kim ◽  
Jun Ho Kho ◽  
Hye Seung Jung ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Transcriptional Activity ◽  
Target Genes ◽  
C2c12 Cells ◽  
C2c12 Myotubes ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mouse Muscle ◽  
Fatty Acid Binding ◽  
Specific Protease

PPAR (peroxisome-proliferator-activated receptor) γ, a nuclear receptor, can be conjugated with SUMO (small ubiquitin-like modifier), which results in the negative regulation of its transcriptional activity. In the present study, we tested whether de-SUMOylation of PPARγ affects the expression of PPARγ target genes in mouse muscle cells and investigated the mechanism by which de-SUMOylation increases PPARγ transcriptional activity. We found that the SUMO-specific protease SENP2 [SUMO1/sentrin/SMT3 (suppressor of mif two 3 homologue 1)-specific peptidase 2] effectively de-SUMOylates PPARγ–SUMO conjugates. Overexpression of SENP2 in C2C12 cells increased the expression of some PPARγ target genes, such as FABP3 (fatty-acid-binding protein 3) and CD36 (fatty acid translocase), both in the absence and presence of rosiglitazone. In contrast, overexpression of SENP2 did not affect the expression of another PPARγ target gene ADRP (adipose differentiation-related protein). De-SUMOylation of PPARγ increased ChIP (chromatin immunoprecipitation) of both a recombinant PPRE (PPAR-response element) and endogenous PPREs of the target genes CD36 and FABP3, but ChIP of the PPRE in the ADRP promoter was not affected by SENP2 overexpression. In conclusion, these results indicate that SENP2 de-SUMOylates PPARγ in myotubes, and de-SUMOylation of PPARγ selectively increases the expression of some PPARγ target genes.

scholarly journals Cevoglitazar, a Novel Peroxisome Proliferator-Activated Receptor-α/γ Dual Agonist, Potently Reduces Food Intake and Body Weight in Obese Mice and Cynomolgus Monkeys

2010 ◽  
Vol 31 (3) ◽  
pp. 404-405
Author(s):  
Hong Chen ◽  
Beatriz Dardik ◽  
Ling Qiu ◽  
Xianglin Ren ◽  
Shari L. Caplan ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Plasma Levels ◽  
Energy Homeostasis ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Peroxisome Proliferator Activated Receptor ◽  
Cynomolgus Monkeys ◽  
Dose Dependent ◽  
Dual Agonist

ABSTRACT Cevoglitazar is a dual agonist for the peroxisome proliferator-activated receptor (PPAR)-α and -γ subtypes. Dual activation of PPARα and -γ is a therapeutic approach in development for the treatment of type 2 diabetes mellitus and diabetic dyslipidemia. In this report, we show that, in addition to improving insulin sensitivity and lipid metabolism like other dual PPAR agonists, cevoglitazar also elicits beneficial effects on energy homeostasis in two animal models of obesity. In leptin-deficient ob/ob mice, administration of cevoglitazar at 0.5, 1, or 2 mg/kg for 18 d led to acute and sustained, dose-dependent reduction of food intake and body weight. Furthermore, plasma levels of glucose and insulin were normalized after 7 d of cevoglitazar treatment at 0.5 mg/kg. Plasma levels of free fatty acids and triglycerides were dose-dependently reduced. In obese and insulin-resistant cynomolgus monkeys, treatment with cevoglitazar at 50 and 500 μg/kg for 4 wk lowered food intake and body weight in a dose-dependent manner. In these animals, cevoglitazar also reduced fasting plasma insulin and, at the highest dose, reduced hemoglobin A1c levels by 0.4%. These preclinical results demonstrate that cevoglitazar holds promise for the treatment of diabetes and obesity-related disorders because of its unique beneficial effect on energy balance in addition to improving glycemic and metabolic control.

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