scholarly journals Corni Fructus Containing Formulation Attenuates Weight Gain in Mice with Diet-Induced Obesity and Regulates Adipogenesis through AMPK

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Hye-Lin Kim ◽  
Yong-Deok Jeon ◽  
Jinbong Park ◽  
Hong-Kun Rim ◽  
Mi-Young Jeong ◽  
...  
Keyword(s):  
Strong Predictor ◽  
Ethanol Extract ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Levels ◽  
Diet Induced Obesity ◽  
Lipin 1 ◽  
Corni Fructus ◽  
Amp Activated Protein Kinase

Obesity is a metabolic disorder characterized by chronic inflammation and dyslipidemia and is a strong predictor for the development of hypertension, diabetes mellitus, and cardiovascular disease. This study examined the antiobesity effect of an ethanol extract of Corni Fructus containing formulation (CDAP), which is a combination of four natural components: Corni Fructus, Dioscoreae Rhizoma, Aurantii Fructus Immaturus, and Platycodonis Radix. The cellular lipid content in 3T3-L1 adipocytes was assessed by Oil Red O staining. Expressions of peroxisome proliferator-activated receptor-γ(PPAR-γ), CCAAT/enhancer-binding protein-α(C/EBP-α), and lipin-1 were determined by real-time RT-PCR. Western blot was used to determine the protein levels of PPAR-γ, C/EBP-α, and AMP-activated protein kinase-α(AMPK-α). The CDAP extract suppressed the differentiation of 3T3-L1 adipocytes by downregulating cellular induction of PPAR-γ, C/EBP-α, and lipin-1. The CDAP extract also significantly upregulated phosphorylation of AMPK-α. Anin vivostudy showed that CDAP induced weight loss in mice with high-fat-diet-induced obesity. These results indicate that CDAP has a potent anti-obesity effect due to the inhibition of adipocyte differentiation and adipogenesis.

scholarly journals Liraglutide suppresses obesity and promotes browning of white fat via miR-27b in vivo and in vitro

2021 ◽  
Vol 49 (11) ◽  
pp. 030006052110550
Author(s):  
Xing Wang ◽  
Shuchun Chen ◽  
Dan Lv ◽  
Zelin Li ◽  
Luping Ren ◽  
...  
Keyword(s):  
Uncoupling Protein ◽  
Density Lipoprotein ◽  
Peroxisome Proliferator ◽  
Sprague Dawley ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Levels ◽  
White Adipocytes ◽  
White Fat

Objective To investigate the effect of liraglutide on the browning of white fat and the suppression of obesity via regulating microRNA (miR)-27b in vivo and in vitro. Methods Sprague-Dawley rats were fed a high-fat (HF) diet and 3T3-L1 pre-adipocytes were differentiated into mature white adipocytes. Rats and mature adipocytes were then treated with different doses of liraglutide. The mRNA and protein levels of browning-associated proteins, including uncoupling protein 1 (UCP1), PR domain containing 16 (PRDM16), CCAAT enhancer binding protein β (CEBPβ), cell death-inducing DFFA-like effector A (CIDEA) and peroxisome proliferator-activated receptor-γ-coactivator 1α (PGC-1α), were detected using quantitative real-time polymerase chain reaction and Western blotting. Results Liraglutide decreased body weight and reduced the levels of blood glucose, triglyceride and low-density lipoprotein cholesterol in HF diet-fed rats. Liraglutide increased the levels of UCP1, PRDM16, CEBPβ, CIDEA and PGC-1α in vivo and vitro. The levels of miR-27b were upregulated in HF diet-fed rats, whereas liraglutide reduced the levels of miR-27b. In vitro, overexpression of miR-27b decreased the mRNA and protein levels of UCP1, PRDM16, CEBPβ, CIDEA and PGC-1α. Transfection with the miR-27b mimics attenuated the effect of liraglutide on the browning of white adipocytes. Conclusion Liraglutide induced browning of white adipose through regulation of miR-27b.

scholarly journals Hyperthyroidism Evokes Myocardial Ceramide Accumulation

2015 ◽  
Vol 35 (2) ◽  
pp. 755-766 ◽  
Author(s):  
Agnieszka Mikłosz ◽  
Bartłomiej Łukaszuk ◽  
Adrian Chabowski ◽  
Filip Rogowski ◽  
Krzysztof Kurek ◽  
...  
Keyword(s):  
Peroxisome Proliferator ◽  
Cardiac Physiology ◽  
Peroxisome Proliferator Activated Receptor ◽  
Sphingosine 1 Phosphate ◽  
Male Wistar Rats ◽  
Hydroxyacyl Coa Dehydrogenase ◽  
Cpt I ◽  
Amp Activated Protein Kinase ◽  
Ceramide Accumulation

Background: Thyroid hormones (THs) are key regulators of cardiac physiology as well as modulators of different cellular signals including the sphingomyelin/ceramide pathway. The objective of this study was to examine the effect of hyperthyroidism on the metabolism of sphingolipids in the muscle heart. Methods: Male Wistar rats were treated for 10 days with triiodothyronine (T3) at a dose of 50µg/100g of body weight. Animals were then anaesthetized and samples of the left ventricle were excised. Results: We have demonstrated that prolonged, in vivo, T3 treatment increased the content of sphinganine (SFA), sphingosine (SFO), ceramide (CER) and sphingomyelin (SM), but decreased the level of sphingosine-1-phosphate (S1P) in cardiac muscle. Accordingly, the changes in sphingolipids content were accompanied by a lesser activity of neutral sphingomyelinase and without significant changes in ceramidases activity. Hyperthyroidism also induced activation of AMP-activated protein kinase (AMPK) with subsequently increased expression of mitochondrial proteins: cytochrome c oxidase IV (COX IV), β-hydroxyacyl-CoA dehydrogenase (β-HAD), carnityne palmitoyltransferase I (CPT I) and nuclear peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α). Conclusions: We conclude that prolonged T3 treatment increases sphingolipids metabolism which is reflected by higher concentration of SFA and CER in heart muscle. Furthermore, hyperthyroidism-induced increase in heart sphingomyelin (SM) concentration might be one of the mechanisms underlying maintenance of CER at relatively low level by its conversion to SM together with decreased S1P content.

scholarly journals The PPARγ ligand rosiglitazone attenuates hypoxia-induced endothelin signaling in vitro and in vivo

2011 ◽  
Vol 301 (6) ◽  
pp. L881-L891 ◽  
Author(s):  
Bum-Yong Kang ◽  
Jennifer M. Kleinhenz ◽  
Tamara C. Murphy ◽  
C. Michael Hart
Keyword(s):  
Transcription Factors ◽  
Hypoxia Inducible Factor ◽  
Cell Counting ◽  
Mouse Lung ◽  
Therapeutic Effects ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Levels

Peroxisome proliferator-activated receptor (PPAR) γ activation attenuates hypoxia-induced pulmonary hypertension (PH) in mice. The current study examined the hypothesis that PPARγ attenuates hypoxia-induced endothelin-1 (ET-1) signaling to mediate these therapeutic effects. To test this hypothesis, human pulmonary artery endothelial cells (HPAECs) were exposed to normoxia or hypoxia (1% O2) for 72 h and treated with or without the PPARγ ligand rosiglitazone (RSG, 10 μM) during the final 24 h of exposure. HPAEC proliferation was measured with MTT assays or cell counting, and mRNA and protein levels of ET-1 signaling components were determined. To explore the role of hypoxia-activated transcription factors, selected HPAECs were treated with inhibitors of hypoxia-inducible factor (HIF)-1α (chetomin) or nuclear factor (NF)-κB (caffeic acid phenethyl ester, CAPE). In parallel studies, male C57BL/6 mice were exposed to normoxia (21% O2) or hypoxia (10% O2) for 3 wk with or without gavage with RSG (10 mg·kg−1·day−1) for the final 10 days of exposure. Hypoxia increased ET-1, endothelin-converting enzyme-1, and endothelin receptor A and B levels in mouse lung and in HPAECs and increased HPAEC proliferation. Treatment with RSG attenuated hypoxia-induced activation of HIF-1α, NF-κB activation, and ET-1 signaling pathway components. Similarly, treatment with chetomin or CAPE prevented hypoxia-induced increases in HPAEC ET-1 mRNA and protein levels. These findings indicate that PPARγ activation attenuates a program of hypoxia-induced ET-1 signaling by inhibiting activation of hypoxia-responsive transcription factors. Targeting PPARγ represents a novel therapeutic strategy to inhibit enhanced ET-1 signaling in PH pathogenesis.

scholarly journals Improved skeletal muscle Ca2+ regulation in vivo following contractions in mice overexpressing PGC-1α

2017 ◽  
Vol 312 (6) ◽  
pp. R1017-R1028 ◽  
Author(s):  
Hiroaki Eshima ◽  
Shinji Miura ◽  
Nanami Senoo ◽  
Koji Hatakeyama ◽  
David C. Poole ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Tibialis Anterior Muscle ◽  
Recovery Period ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Levels ◽  
S 100 ◽  
Intracellular Ca ◽  
Related Proteins

In skeletal muscle, resting intracellular Ca2+ concentration ([Ca2+]i) homeostasis is exquisitely regulated by Ca2+ transport across the sarcolemmal, mitochondrial, and sarcoplasmic reticulum (SR) membranes. Of these three systems, the relative importance of the mitochondria in [Ca2+]i regulation remains poorly understood in in vivo skeletal muscle. We tested the hypothesis that the capacity for Ca2+ uptake by mitochondria is a primary factor in determining [Ca2+]i regulation in muscle at rest and following contractions. Tibialis anterior muscle of anesthetized peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α)-overexpressing (OE, increased mitochondria model) and wild-type (WT) littermate mice was exteriorized in vivo and loaded with the fluorescent probe fura 2-AM, and Rhod 2-AM Ca2+ buffering and mitochondrial [Ca2+] were evaluated at rest and during recovery from fatiguing tetanic contractions induced by electrical stimulation (120 s, 100 Hz). In addition, the effects of pharmacological inhibition of SR (thapsigargin) and mitochondrial [carbonyl cyanide- 4-(trifluoromethoxy) phenylhydrazone (FCCP)] function were examined at rest. [Ca2+]i in WT remained elevated for the entire postcontraction recovery period (+6 ± 1% at 450 s), but in PGC-1α OE [Ca2+]i returned to resting baseline within 150 s. Thapsigargin immediately and substantially increased resting [Ca2+]i in WT, whereas in PGC-1α OE this effect was delayed and markedly diminished (WT, +12 ± 3; PGC-1α OE, +1 ± 2% at 600 s after thapsigargin treatment, P < 0.05). FCCP abolished this improvement of [Ca2+]i regulation in PGC-1α OE. Mitochondrial [Ca2+] accumulation was observed in PGC-1α OE following contractions and thapsigargin treatment. In the SR, PGC-1α OE downregulated SR Ca2+-ATPase 1 (Ca2+ uptake) and parvalbumin (Ca2+ buffering) protein levels, whereas mitochondrial Ca2+ uptake-related proteins (Mfn1, Mfn2, and mitochondrial Ca2+ uniporter) were upregulated. These data demonstrate a heretofore unappreciated role for skeletal muscle mitochondria in [Ca2+]i regulation in vivo following fatiguing tetanic contractions and at rest.

Antagonism of peroxisome proliferator-activated receptor γ prevents high-fat diet-induced obesity in vivo

2006 ◽  
Vol 72 (1) ◽  
pp. 42-52 ◽  
Author(s):  
Ryosuke Nakano ◽  
Eiji Kurosaki ◽  
Shigeru Yoshida ◽  
Masanori Yokono ◽  
Akiyoshi Shimaya ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Peroxisome Proliferator ◽  
High Fat ◽  
Peroxisome Proliferator Activated Receptor ◽  
Diet Induced Obesity

scholarly journals Glucagon and lipid interactions in the regulation of hepatic AMPK signaling and expression of PPARα and FGF21 transcripts in vivo

2010 ◽  
Vol 299 (4) ◽  
pp. E607-E614 ◽  
Author(s):  
Eric D. Berglund ◽  
Li Kang ◽  
Robert S. Lee-Young ◽  
Clinton M. Hasenour ◽  
Daniel G. Lustig ◽  
...  
Keyword(s):  
Whole Body ◽  
Fibroblast Growth Factor 21 ◽  
Peroxisome Proliferator ◽  
Glucagon Receptor ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ampk Signaling ◽  
Downstream Target ◽  
Amp Activated Protein Kinase ◽  
Fgf21 Expression

Hepatic glucagon action increases in response to accelerated metabolic demands and is associated with increased whole body substrate availability, including circulating lipids. The hypothesis that increases in hepatic glucagon action stimulate AMP-activated protein kinase (AMPK) signaling and peroxisome proliferator-activated receptor-α (PPARα) and fibroblast growth factor 21 (FGF21) expression in a manner modulated by fatty acids was tested in vivo. Wild-type ( gcgr+/+) and glucagon receptor-null ( gcgr−/−) littermate mice were studied using an 18-h fast, exercise, and hyperglucagonemic-euglycemic clamps plus or minus increased circulating lipids. Fasting and exercise in gcgr+/+, but not gcgr−/− mice, increased hepatic phosphorylated AMPKα at threonine 172 (p-AMPKThr172) and PPARα and FGF21 mRNA. Clamp results in gcgr+/+ mice demonstrate that hyperlipidemia does not independently impact or modify glucagon-stimulated increases in hepatic AMP/ATP, p-AMPKThr172, or PPARα and FGF21 mRNA. It blunted glucagon-stimulated acetyl-CoA carboxylase phosphorylation, a downstream target of AMPK, and accentuated PPARα and FGF21 expression. All effects were absent in gcgr−/− mice. These findings demonstrate that glucagon exerts a critical regulatory role in liver to stimulate pathways linked to lipid metabolism in vivo and shows for the first time that effects of glucagon on PPARα and FGF21 expression are amplified by a physiological increase in circulating lipids.

scholarly journals Temporal recruitment of CCAAT/enhancer-binding proteins to early and late adipogenic promoters in vivo

2006 ◽  
Vol 36 (1) ◽  
pp. 139-151 ◽  
Author(s):  
N Salma ◽  
H Xiao ◽  
A N Imbalzano
Keyword(s):  
Dna Binding ◽  
Chromatin Immunoprecipitation ◽  
Binding Capacity ◽  
Regulatory Sequences ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Levels ◽  
Enhancer Binding Protein ◽  
Kinetics Of

The CCAAT/enhancer-binding protein (C/EBP) family of transcriptional regulators is critically important for the activation of adipogenic genes during differentiation. The C/EBPβ and δ isoforms are rapidly induced upon adipocyte differentiation and are responsible for activating the adipogenic regulators C/EBPα and peroxisome proliferator activated receptor (PPAR)γ2, which together activate the majority of genes expressed in differentiating adipocytes. However, mitosis is required following the induction of adipogenesis, and the activation of C/EBPα and PPARγ2 gene expression is delayed until cell division is underway. Previous studies have used electromobility shift assays to suggest that this delay is due, at least in part, to a delay between the induction of C/EBPβ protein levels and the acquisition of DNA binding capacity by C/EBPβ. Here we used in vivo chromatin immunoprecipitation analysis of the C/EBPα, PPARγ2, resistin, adiponectin, and leptin promoters to examine the kinetics of C/EBP protein binding to adipogenic genes in differentiating cells. In contrast to prior studies, we determined that C/EBPβ and δ were bound to endogenous regulatory sequences controlling the expression of these genes within 1–4 h of adipogenic induction. These results indicated that C/EBPβ and δ bind not only to genes that are induced early in the adipogenic process but also to genes that are induced much later during differentiation, without a delay between induction of C/EBP protein levels and DNA binding by these proteins. We also showed that each of the genes examined undergoes a transition in vivo from early occupancy by C/EBPβ and δ to occupancy by C/EBPα at times that correlate with the induction of C/EBPα protein levels, demonstrating the generality of the transition during adipogenesis and indicating that the binding of specific C/EBP isoforms does not correlate with timing of expression from each gene. We have concluded that C/EBP family members bind to adipogenic genes in vivo in a manner that follows the induction of C/EBP protein synthesis.

scholarly journals Impaired Adipogenesis Caused by a Mutated Thyroid Hormone α1 Receptor

2007 ◽  
Vol 27 (6) ◽  
pp. 2359-2371 ◽  
Author(s):  
Hao Ying ◽  
Osamu Araki ◽  
Fumihiko Furuya ◽  
Yasuhito Kato ◽  
Sheue-Yann Cheng
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormone Receptor ◽  
Dominant Negative ◽  
Dominant Negative Mutant ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Levels ◽  
Reduced Body ◽  
X Receptors

ABSTRACT Thyroid hormone (T3) is critical for growth, differentiation, and maintenance of metabolic homeostasis. Mice with a knock-in mutation in the thyroid hormone receptor α gene (TRα1PV) were created previously to explore the roles of mutated TRα1 in vivo. TRα1PV is a dominant negative mutant with a frameshift mutation in the carboxyl-terminal 14 amino acids that results in the loss of T3 binding and transcription capacity. Homozygous knock-in TRα1PV/PV mice are embryonic lethal, and heterozygous TRα1PV/+ mice display the striking phenotype of dwarfism. These mutant mice provide a valuable tool for identifying the defects that contribute to dwarfism. Here we show that white adipose tissue (WAT) mass was markedly reduced in TRα1PV/+ mice. The expression of peroxisome proliferator-activated receptor γ (PPARγ), the key regulator of adipogenesis, was repressed at both mRNA and protein levels in WAT of TRα1PV/+ mice. Moreover, TRα1PV acted to inhibit the transcription activity of PPARγ by competition with PPARγ for binding to PPARγ response elements and for heterodimerization with the retinoid X receptors. The expression of TRα1PV blocked the T3-dependent adipogenesis of 3T3-L1 cells and repressed the expression of PPARγ. Thus, mutations of TRα1 severely affect adipogenesis via cross talk with PPARγ signaling. The present study suggests that defects in adipogenesis could contribute to the phenotypic manifestation of reduced body weight in TRα1PV/+ mice.

scholarly journals Labisia pumilaUpregulates Peroxisome Proliferator-Activated Receptor Gamma Expression in Rat Adipose Tissues and 3T3-L1 Adipocytes

2013 ◽  
Vol 2013 ◽  
pp. 1-7
Author(s):  
Fazliana Mansor ◽  
Harvest F. Gu ◽  
Claes-Göran Östenson ◽  
Louise Mannerås-Holm ◽  
Elisabet Stener-Victorin ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary ◽  
Mrna Level ◽  
Water Extract ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Levels

Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand-activated transcription factor that regulates lipid and glucose metabolism. We investigated the effects ofLabisia pumila(LP) standardized water extract on PPARgamma transcriptional activity in adipocytesin vitroandin vivo. We used a rat model of dihydrotestosterone- (DHT-) induced polycystic ovary syndrome (PCOS), a condition characterized by insulin resistance. At 9 weeks of age, the PCOS rats were randomly subdivided into two groups: PCOS-LP (50 mg/kg/day of LP) and PCOS-control (1 mL of deionised water) for 4-5 weeks on the same schedule. Real-time RT-PCR was performed to determine the PPARgamma mRNA levels. LP upregulated PPARgamma mRNA level by 40% in the PCOS rats. Western blot analysis further demonstrated the increased PPARgamma protein levels in parallel with upregulation in mRNA. These observations were further proven by adipocytes culture. Differentiated 3T3-L1 adipocytes were treated with final concentration of 100 μg/mL LP and compared to untreated control and 10 μM of rosiglitazone (in type of thiazolidinediones). LP increased PPARgamma expressions at both mRNA and protein levels and enhanced the effect of glucose uptake in the insulin-resistant cells. The data suggest that LP may ameliorate insulin resistance in adipocytes via the upregulation of PPARgamma pathway.

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