scholarly journals Rhein Reduces Fat Weight indb/dbMouse and Prevents Diet-Induced Obesity in C57Bl/6 Mouse through the Inhibition of PPARγSignaling

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Yu Zhang ◽  
Shengjie Fan ◽  
Na Hu ◽  
Ming Gu ◽  
Chunxiao Chu ◽  
...  
Keyword(s):  
Target Genes ◽  
Fasting Blood Glucose ◽  
Peroxisome Proliferator ◽  
Brown Adipocytes ◽  
Peroxisome Proliferator Activated Receptor ◽  
Glucose Levels ◽  
Rheum Palmatum ◽  
Diet Induced Obesity ◽  
Blood Glucose Levels ◽  
Underlying Mechanisms

Rheum palmatumhas been used most frequently in the weight-reducing formulae in traditional Chinese medicine. However, the components ofRheum palmatumthat play the antiobesity role are still uncertain. Here, we tested the weight-reducing effect of two majorRheum palmatumcompounds ondb/dbmouse. We found that rhein (100 mg kg−1 day−1), but not emodin, reduced the fat weight indb/dbmouse. Using diet-induced obese (DIO) C57BL/6 mice, we identified that rhein blocked high-fat diet-induced obesity, decreased fat mass and the size of white and brown adipocytes, and lowered serum cholesterol, LDL cholesterol, and fasting blood glucose levels in the mice. To elucidate the underlying mechanisms, we used reporter assay and gene expression analysis and found that rhein inhibited peroxisome proliferator-activated receptorγ(PPARγ) transactivity and the expression of its target genes, suggesting that rhein may act as a PPARγantagonist. Our data indicate that rhein may be a promising choice for antiobesity therapy.

Abstract P172: Activation of Pgc1α by EET Stimulates Insulin Sensitivity, Normalizes Blood Pressure and Increases Mitochondrial Oxphos in Obese Mice

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Shailendra P Singh ◽  
Maayan Waldman ◽  
Joseph Schragenheim ◽  
Lars Bellner ◽  
Jian Cao ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Insulin Sensitivity ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Function ◽  
Fasting Blood Glucose ◽  
Cardiovascular Complications ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Glucose Levels ◽  
Obesity In Mice

Background/Objectives: Obesity is a risk factor in the development of type 2 diabetes mellitus (DM2), which is associated with increased morbidity and mortality, predominantly as a result of cardiovascular complications. Increased adiposity is a systemic condition characterized by increased oxidative stress (ROS), inflammation, inhibition of anti-oxidant genes such as HO-1 and increased degradation of epoxyeicosatrienoic acids (EETs). Hypothesis: We postulate that EETs increase peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) activity, which controls mitochondrial function, oxidative metabolism and may also increase antioxidants and HO-1 gene expression. Methods: C57/B16 mice were fed a high fat (HF) diet for 26 wks. The protocol comprised three groups: A) WT, B) HF control and C) HF-treated with EET agonist (EET-A). Renal and visceral fat tissues were harvested to measure signaling protein. Consumption was measured at 6 and 24 wks. Mice were used to assess insulin levels, insulin sensitivity, blood pressure and mitochondrial OXPHOS and mitochondrial biogenesis (Mfn1, 2 and Opa1), and oxygen consumption (VO 2 ). Results: Animals on a HF diet exhibited increased body weight, fat content, fasting blood glucose levels, systolic blood pressure (BP) and a significant reduction in VO 2 . Administration of EET-A to HF-fed mice decreased the RQ (VCO 2 /VO 2 ) ratio and normalized BP. The HF diet produced increased levels of the adipogenic markers MEST, aP2, C/EBPα and FAS. EET-A attenuated these perturbations through an increase in renal and adipose tissue PGC1α levels. The EET-mediated HO-1 induction increased mitochondrial function as measured by OXPHOS, MnSOD and thermogenic genes, TFAM, UCP1 and SIRT 1. EET-A also increased adiponectin levels, and insulin receptor phosphorylation IRP Tyr 972 and 1146 and normalized glucose levels. Conclusion: These data show that an EET agonist increased PGC-1α-HO-1 levels thereby providing metabolic protection and increased VO 2 consumption in HF-induced obesity in mice. This novel finding suggests that the EET-mediated PGC-1α activation is essential to increase HO-1 levels, mitochondrial biogenesis, and to decrease mitochondrial ROS and adiposity.

scholarly journals Inhibition of HDAC3 promotes ligand-independent PPARγ activation by protein acetylation

2014 ◽  
Vol 53 (2) ◽  
pp. 191-200 ◽  
Author(s):  
Xiaoting Jiang ◽  
Xin Ye ◽  
Wei Guo ◽  
Hongyun Lu ◽  
Zhanguo Gao
Keyword(s):  
Insulin Sensitivity ◽  
Posttranslational Modifications ◽  
Target Genes ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Histone Deacetylase 3 ◽  
Protein Inhibition ◽  
Diet Induced Obesity ◽  
Exogenous Ligands

Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor whose activation is dependent on a ligand. PPARγ activation by exogenous ligands, such as thiazolidinediones (TZDs), is a strategy in the treatment of type 2 diabetes mellitus for the improvement of insulin sensitivity. In addition to a ligand, PPARγ function is also regulated by posttranslational modifications, such as phosphorylation, sumoylation, and ubiquitination. Herein, we report that the PPARγ protein is modified by acetylation, which induces the PPARγ function in the absence of an external ligand. We observed that histone deacetylase 3 (HDAC3) interacted with PPARγ to deacetylate the protein. In immunoprecipitation assays, the HDAC3 protein was associated with the PPARγ protein. Inhibition of HDAC3 using RNAi-mediated knockdown or HDAC3 inhibitor increased acetylation of the PPARγ protein. Furthermore, inhibition of HDAC3 enhanced the expression of PPARγ target genes such as adiponectin and aP2. The expression was associated with an increase in glucose uptake and insulin signaling in adipocytes. HDAC3 inhibition enhanced lipid accumulation during differentiation of adipocytes. PPARγ acetylation was also induced by pioglitazone and acetylation was required for PPARγ activation. In the absence of TZDs, the acetylation from HDAC3 inhibition was sufficient to induce the transcriptional activity of PPARγ. Treating diet-induced obesity mice with HDAC3 inhibitor or pioglitazone for 2 weeks significantly improved high-fat-diet-induced insulin resistance. Our results indicate that acetylation of PPARγ is a ligand-independent mechanism of PPARγ activation. HDAC3 inhibitor is a potential PPARγ activator for the improvement of insulin sensitivity.

scholarly journals The endocrine disruptor mono-(2-ethylhexyl)phthalate promotes adipocyte differentiation and induces obesity in mice

2012 ◽  
Vol 32 (6) ◽  
pp. 619-629 ◽  
Author(s):  
Chanjuan Hao ◽  
Xuejia Cheng ◽  
Hongfei Xia ◽  
Xu Ma
Keyword(s):  
Target Genes ◽  
Adipocyte Differentiation ◽  
Cell Model ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Peroxisome Proliferator Activated Receptor ◽  
Glucose Levels ◽  
Ethylhexyl Phthalate

The environmental obesogen hypothesis proposes that exposure to endocrine disruptors during developmental ‘window’ contributes to adipogenesis and the development of obesity. MEHP [mono-(2-ethylhexyl) phthalate], a metabolite of the widespread plasticizer DEHP [di-(2-ethylhexyl) phthalate], has been found in exposed organisms and identified as a selective PPARγ (peroxisome-proliferator-activated receptor γ) modulator. However, implication of MEHP on adipose tissue development has been poorly investigated. In the present study, we show the dose-dependent effects of MEHP on adipocyte differentiation and GPDH (glycerol-3-phosphate dehydrogenase) activity in the murine 3T3-L1 cell model. MEHP induced the expression of PPARγ as well as its target genes required for adipogenesis in vitro. Moreover, MEHP perturbed key regulators of adipogenesis and lipogenic pathway in vivo. In utero exposure to a low dose of MEHP significantly increased b.w. (body weight) and fat pad weight in male offspring at PND (postnatal day) 60. In addition, serum cholesterol, TAG (triacylglycerol) and glucose levels were also significantly elevated. These results suggest that perinatal exposure to MEHP may be expected to increase the incidence of obesity in a sex-dependent manner and can act as a potential chemical stressor for obesity and obesity-related disorders.

scholarly journals A propolis-derived small molecule ameliorates metabolic syndrome in obese mice by targeting the CREB/CRTC2 transcriptional complex

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Yaqiong Chen ◽  
Jiang Wang ◽  
Yibing Wang ◽  
Pengfei Wang ◽  
Zan Zhou ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Insulin Sensitivity ◽  
Fasting Blood Glucose ◽  
Obese Mice ◽  
Glucose Levels ◽  
Diet Induced Obesity ◽  
Blood Glucose Levels ◽  
Suitable Target ◽  
Artepillin C ◽  
Transcriptional Complex

AbstractThe molecular targets and mechanisms of propolis ameliorating metabolic syndrome are not fully understood. Here, we report that Brazilian green propolis reduces fasting blood glucose levels in obese mice by disrupting the formation of CREB/CRTC2 transcriptional complex, a key regulator of hepatic gluconeogenesis. Using a mammalian two-hybrid system based on CREB-CRTC2, we identify artepillin C (APC) from propolis as an inhibitor of CREB-CRTC2 interaction. Without apparent toxicity, APC protects mice from high fat diet-induced obesity, decreases fasting glucose levels, enhances insulin sensitivity and reduces lipid levels in the serum and liver by suppressing CREB/CRTC2-mediated both gluconeogenic and SREBP transcriptions. To develop more potential drugs from APC, we designed and found a novel compound, A57 that exhibits higher inhibitory activity on CREB-CRTC2 association and better capability of improving insulin sensitivity in obese animals, as compared with APC. In this work, our results indicate that CREB/CRTC2 is a suitable target for developing anti-metabolic syndrome drugs.

scholarly journals CREBH Maintains Circadian Glucose Homeostasis by Regulating Hepatic Glycogenolysis and Gluconeogenesis

2017 ◽  
Vol 37 (14) ◽  
Author(s):  
Hyunbae Kim ◽  
Ze Zheng ◽  
Paul D. Walker ◽  
Gregory Kapatos ◽  
Kezhong Zhang
Keyword(s):  
Blood Glucose ◽  
Glucose Homeostasis ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Liver Glycogen ◽  
Glycogen Storage ◽  
Hepatic Glycogen ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Glucose Levels ◽  
Blood Glucose Levels

ABSTRACT Cyclic AMP-responsive element binding protein, hepatocyte specific (CREBH), is a liver-enriched, endoplasmic reticulum-tethered transcription factor known to regulate the hepatic acute-phase response and lipid homeostasis. In this study, we demonstrate that CREBH functions as a circadian transcriptional regulator that plays major roles in maintaining glucose homeostasis. The proteolytic cleavage and posttranslational acetylation modification of CREBH are regulated by the circadian clock. Functionally, CREBH is required in order to maintain circadian homeostasis of hepatic glycogen storage and blood glucose levels. CREBH regulates the rhythmic expression of the genes encoding the rate-limiting enzymes for glycogenolysis and gluconeogenesis, including liver glycogen phosphorylase (PYGL), phosphoenolpyruvate carboxykinase 1 (PCK1), and the glucose-6-phosphatase catalytic subunit (G6PC). CREBH interacts with peroxisome proliferator-activated receptor α (PPARα) to synergize its transcriptional activities in hepatic gluconeogenesis. The acetylation of CREBH at lysine residue 294 controls CREBH-PPARα interaction and synergy in regulating hepatic glucose metabolism in mice. CREBH deficiency leads to reduced blood glucose levels but increases hepatic glycogen levels during the daytime or upon fasting. In summary, our studies revealed that CREBH functions as a key metabolic regulator that controls glucose homeostasis across the circadian cycle or under metabolic stress.

scholarly journals Immunomodulatory Role of an Ayurvedic Formulation on Imbalanced Immunometabolics during Inflammatory Responses of Obesity and Prediabetic Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Kamiya Tikoo ◽  
Shashank Misra ◽  
Kanury V. S. Rao ◽  
Parul Tripathi ◽  
Sachin Sharma
Keyword(s):  
Inflammatory Responses ◽  
Fasting Blood Glucose ◽  
Normal Diet ◽  
Immunological Parameters ◽  
Glucose Levels ◽  
Inflammatory Conditions ◽  
Diet Induced Obesity ◽  
Blood Glucose Levels ◽  
Sugar Levels ◽  
Major Factors

Kal-1 is a polyherbal decoction of seven different natural ingredients, traditionally used in controlling sugar levels, inflammatory conditions particularly regulating metabolic and immunoinflammatory balance which are the major factors involved in obesity and related diseases. In the present study, we aimed to investigate the effect of Kal-1 (an abbreviation derived from the procuring source) on diet-induced obesity and type II diabetes using C57BL/6J mice as a model. The present study was performed with two experimental groups involving obese and prediabetic mice as study animals. In one, the mice were fed on high-fat with increased sucrose diet, and different amounts (5, 20, and 75 μL) of Kal-1 were administered with monitoring of disease progression over a period of 21 weeks whereas in the second group the mice were first put on the same diet for 21 weeks and then treated with the same amounts of Kal-1. A significant reduction in body weight, fat pads, fasting blood glucose levels, insulin levels, biochemical parameters, immunological parameters, and an array of pro- and anticytokines was observed in obese and diabetic mice plus Kal-1 than control (lean) mice fed on normal diet. In conclusion, Kal-1 has immunomodulatory potential for diet-induced obesity and associated metabolic disorders.

scholarly journals Citrus ichangensisPeel Extract Exhibits Anti-Metabolic Disorder Effects by the Inhibition of PPARγand LXR Signaling in High-Fat Diet-Induced C57BL/6 Mouse

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Xiaobo Ding ◽  
Shengjie Fan ◽  
Yan Lu ◽  
Yu Zhang ◽  
Ming Gu ◽  
...  
Keyword(s):  
Fatty Acid Synthase ◽  
Target Genes ◽  
Body Weight Gain ◽  
Density Lipoprotein ◽  
Chow Diet ◽  
Peroxisome Proliferator ◽  
High Fat ◽  
Nutritional Disorder ◽  
Peroxisome Proliferator Activated Receptor ◽  
Diet Induced Obesity

Obesity is a common nutritional disorder associated with type 2 diabetes, cardiovascular diseases, dyslipidemia, and certain cancers. In this study, we investigated the effects ofCitrus ichangensispeel extract (CIE) in high-fat (HF) diet-induced obesity mice. Female C57BL/6 mice were fed a chow diet or an HF diet alone or supplemented with 1% w/w CIE for 8 weeks. We found that CIE treatment could lower blood glucose level and improve glucose tolerance. In the HF+CIE group, body weight gain, serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c) levels, and liver triglyceride (TG) and TC concentrations were significantly (P<0.05) decreased relative to those in the HF group. To elucidate the mechanism of CIE on the metabolism of glucose and lipid, related genes expression in liver were examined. In liver tissue, CIE significantly decreased the mRNA expression levels of peroxisome proliferator-activated receptorγ(PPARγ) and its target genes, such as fatty acid synthase (FAS) and acyl-CoA oxidase (ACO). Moreover, CIE also decreased the expression of liver X receptor (LXR)αandβwhich are involved in lipid and glucose metabolism. These results suggest that CIE administration could alleviate obesity and related metabolic disorders in HF diet-induced obesity mice through the inhibition of PPARγand LXR signaling.

scholarly journals Effects of Baccharin Isolated from Brazilian Green Propolis on Adipocyte Differentiation and Hyperglycemia in ob/ob Diabetic Mice

2021 ◽  
Vol 22 (13) ◽  
pp. 6954
Author(s):  
Akio Watanabe ◽  
Marília Oliveira de Almeida ◽  
Yusuke Deguchi ◽  
Ryuzo Kozuka ◽  
Caroline Arruda ◽  
...  
Keyword(s):  
Target Genes ◽  
Adipocyte Differentiation ◽  
Biological Activities ◽  
Intraperitoneal Administration ◽  
Peroxisome Proliferator ◽  
Cinnamic Acid Derivative ◽  
Peroxisome Proliferator Activated Receptor ◽  
Glucose Levels ◽  
Glycerol 3 Phosphate Dehydrogenase ◽  
Brazilian Green Propolis

Propolis is a honeybee product with various biological activities, including antidiabetic effects. We previously reported that artepillin C, a prenylated cinnamic acid derivative isolated from Brazilian green propolis, acts as a peroxisome proliferator-activated receptor γ (PPARγ) ligand and promotes adipocyte differentiation. In this study, we examined the effect of baccharin, another major component of Brazilian green propolis, on adipocyte differentiation. The treatment of mouse 3T3-L1 preadipocytes with baccharin resulted in increased lipid accumulation, cellular triglyceride levels, glycerol-3-phosphate dehydrogenase activity, and glucose uptake. The mRNA expression levels of PPARγ and its target genes were also increased by baccharin treatment. Furthermore, baccharin enhanced PPARγ-dependent luciferase activity, suggesting that baccharin promotes adipocyte differentiation via PPARγ activation. In diabetic ob/ob mice, intraperitoneal administration of 50 mg/kg baccharin significantly improved blood glucose levels. Our results suggest that baccharin has a hypoglycemic effect on glucose metabolic disorders, such as type 2 diabetes mellitus.

scholarly journals Cyclin D3 Promotes Adipogenesis through Activation of Peroxisome Proliferator-Activated Receptor γ

2005 ◽  
Vol 25 (22) ◽  
pp. 9985-9995 ◽  
Author(s):  
David A. Sarruf ◽  
Irena Iankova ◽  
Anna Abella ◽  
Said Assou ◽  
Stéphanie Miard ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Nuclear Receptor ◽  
Cell Cycle Progression ◽  
Target Genes ◽  
Direct Interaction ◽  
Mitotic Division ◽  
Cyclin D3 ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Diet Induced Obesity

ABSTRACT In addition to their role in cell cycle progression, new data reveal an emerging role of D-type cyclins in transcriptional regulation and cellular differentiation processes. Using 3T3-L1 cell lines to study adipogenesis, we observed an up-regulation of cyclin D3 expression throughout the differentiation process. Surprisingly, cyclin D3 was only minimally expressed during the initial stages of adipogenesis, when mitotic division is prevalent. This seemingly paradoxical expression led us to investigate a potential cell cycle-independent role for cyclin D3 during adipogenesis. We show here a direct interaction between cyclin D3 and the nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ). Our experiments reveal cyclin D3 acts as a ligand-dependent PPARγ coactivator, which, together with its cyclin-dependent kinase partner, phosphorylates the A-B domain of the nuclear receptor. Overexpression and knockdown studies with cyclin D3 had marked effects on PPARγ activity and subsequently on adipogenesis. Chromatin immunoprecipitation assays confirm the participation of cyclin D3 in the regulation of PPARγ target genes. We show that cyclin D3 mutant mice are protected from diet-induced obesity, display smaller adipocytes, have reduced adipogenic gene expression, and are insulin sensitive. Our results indicate that cyclin D3 is an important factor governing adipogenesis and obesity.

scholarly journals Comparative Study of 3 Different Brands of Glimperide

2020 ◽  
Keyword(s):  
Blood Glucose ◽  
Ppar Gamma ◽  
Dissolution Time ◽  
Peroxisome Proliferator ◽  
Disintegration Time ◽  
Peroxisome Proliferator Activated Receptor ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Weight Variation

Glimepiride is an antidiabetic agent used for lowering blood glucose levels. It induces the activity of peroxisome proliferator-activated receptor-gamma (PPAR gamma). It lowers blood glucose levels by binding to ATP-sensitive potassium channel receptors on the surface of pancreatic cells. The purpose of this study was to perform a comparative analysis of different physicochemical parameters (weight variation, hardness, thickness, friability, disintegration time, and dissolution time) of 3 different commercially available brands of glimepiride in the market. Statistical analysis revealed minor variations in the results. It was found that GETRYL showed the highest % dissolution among all the 3 brands whereas AMARYL took the least time to disintegrate. According to the results of the friability test, Diabold shows the highest stability in the friabilator. However, all 3 brands complied with the official pharmacopoeial limits. The quality of the drug largely influences its therapeutic activity. Hence, owing to the similar physicochemical profile, all the 3 brands can be interchangeably used.

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