scholarly journals Noradrenaline represses PPAR (peroxisome-proliferator-activated receptor) γ2 gene expression in brown adipocytes: intracellular signalling and effects on PPARγ2 and PPARγ1 protein levels

2004 ◽  
Vol 382 (2) ◽  
pp. 597-606 ◽  
Author(s):  
Eva M. LINDGREN ◽  
Ronni NIELSEN ◽  
Natasa PETROVIC ◽  
Anders JACOBSSON ◽  
Susanne MANDRUP ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Kinase ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Down Regulation ◽  
Brown Adipocytes ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Levels ◽  
Pparγ Gene ◽  
Kinase A

PPAR (peroxisome-proliferator-activated receptor) γ is expressed in brown and white adipose tissues and is involved in the control of differentiation and proliferation. Noradrenaline stimulates brown pre-adipocyte proliferation and brown adipocyte differentiation. The aim of the present study was thus to investigate the influence of noradrenaline on PPARγ gene expression in brown adipocytes. In primary cultures of brown adipocytes, PPARγ2 mRNA levels were 20-fold higher than PPARγ1 mRNA levels. PPARγ expression occurred during both the proliferation and the differentiation phases, with the highest mRNA levels being found at the time of transition between the phases. PPARγ2 mRNA levels were downregulated by noradrenaline treatment (EC50, 0.1 μM) in both proliferative and differentiating cells, with a lagtime of 1 h and lasting up to 4 h, after which expression gradually recovered. The down-regulation was β-adrenoceptor-induced and intracellularly mediated via cAMP and protein kinase A; the signalling pathway did not involve phosphoinositide 3-kinase, Src, p38 mitogen-activated protein kinase or extracellular-signal-regulated kinases 1 and 2. Treatment of the cells with the protein synthesis inhibitor cycloheximide not only abolished the noradrenaline-induced down-regulation of PPARγ2 mRNA, but also in itself induced PPARγ2 hyperexpression. The down-regulation was probably the result of suppression of transcription. The down-regulation of PPARγ2 mRNA resulted in similar down-regulation of PPARγ2 and phosphoPPARγ2 protein levels. Remarkably, the level of PPARγ1 protein was similar to that of PPARγ2 (despite almost no PPARγ1 mRNA), and the down-regulation by noradrenaline demonstrated similar kinetics to that of PPARγ2; thus PPARγ1 was apparently translated from the PPARγ2 template. It is suggested that β-adrenergic stimulation via cAMP and protein kinase A represses PPARγ gene expression, leading to reduction of PPARγ2 mRNA levels, which is then reflected in down-regulated levels of PPARγ2, phosphoPPARγ2 and PPARγ1.

scholarly journals Protein Kinase A/CREB Signaling Prevents Adriamycin-Induced Podocyte Apoptosis via Upregulation of Mitochondrial Respiratory Chain Complexes

2017 ◽  
Vol 38 (1) ◽  
Author(s):  
Kewei Xie ◽  
Mingli Zhu ◽  
Peng Xiang ◽  
Xiaohuan Chen ◽  
Ayijiaken Kasimumali ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Respiratory Chain ◽  
Mitochondrial Respiratory Chain ◽  
Peroxisome Proliferator ◽  
Respiratory Chain Complexes ◽  
Peroxisome Proliferator Activated Receptor ◽  
Kinase A ◽  
Mitochondrial Respiratory

ABSTRACT Previous work showed that the activation of protein kinase A (PKA) signaling promoted mitochondrial fusion and prevented podocyte apoptosis. The cAMP response element binding protein (CREB) is the main downstream transcription factor of PKA signaling. Here we show that the PKA agonist 8-(4-chlorophenylthio)adenosine 3′,5′-cyclic monophosphate–cyclic AMP (pCPT-cAMP) prevented the production of adriamycin (ADR)-induced reactive oxygen species and apoptosis in podocytes, which were inhibited by CREB RNA interference (RNAi). The activation of PKA enhanced mitochondrial function and prevented the ADR-induced decrease of mitochondrial respiratory chain complex I subunits, NADH-ubiquinone oxidoreductase complex (ND) 1/3/4 genes, and protein expression. Inhibition of CREB expression alleviated pCPT-cAMP-induced ND3, but not the recovery of ND1/4 protein, in ADR-treated podocytes. In addition, CREB RNAi blocked the pCPT-cAMP-induced increase in ATP and the expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1-α). The chromatin immunoprecipitation assay showed enrichment of CREB on PGC1-α and ND3 promoters, suggesting that these promoters are CREB targets. In vivo, both an endogenous cAMP activator (isoproterenol) and pCPT-cAMP decreased the albumin/creatinine ratio in mice with ADR nephropathy, reduced glomerular oxidative stress, and retained Wilm's tumor suppressor gene 1 (WT-1)-positive cells in glomeruli. We conclude that the upregulation of mitochondrial respiratory chain proteins played a partial role in the protection of PKA/CREB signaling.

scholarly journals Effect of Salusin-ß on Peroxisome Proliferator-Activated Receptor Gamma Gene Expression in Vascular Smooth Muscle Cells and its Possible Mechanism

2015 ◽  
Vol 36 (6) ◽  
pp. 2466-2479 ◽  
Author(s):  
XiaoLe Xu ◽  
Mengzi He ◽  
Tingting Liu ◽  
Yi Zeng ◽  
Wei Zhang
Keyword(s):  
Gene Expression ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Nuclear Translocation ◽  
Muscle Cells ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pparγ Gene

Background/Aims: salusin-ß is considered to be a potential pro-atherosclerotic factor. Regulation and function of vascular smooth muscle cells (VSMCs) are important in the progression of atherosclerosis. Peroxisome proliferator-activated receptor gamma (PPARγ) exerts a vascular protective role beyond its metabolic effects. Salusin-ß has direct effects on VSMCs. The aim of the present study was to assess the effect of salusin-ß on PPARγ gene expression in primary cultured rat VSMCs. Methods: Western blotting analysis, real-time PCR and transient transfection approach were used to determine expression of target proteins. Specific protein knockdown was performed with siRNA transfection. Cell proliferation was determined by 5-bromo-2'-deoxyuridine incorporation. The levels of inflammation indicators interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a) were determined using enzyme-linked immunosorbent assay. Results: Salusin-ß negatively regulated PPARγ gene expression at protein, mRNA and gene promoter level in VSMCs. The inhibitory effect of salusin-ß on PPARγ gene expression contributed to salusin-ß-induced VSMCs proliferation and inflammation in vitro. IγBa-NF-γB activation, but not NF-γB p50 or p65, mediated the salusin-ß-induced inhibition of PPARγ gene expression. Salusin-ß induced nuclear translocation of histone deacetylase 3 (HDAC3). HDAC3 siRNA prevented salusin-ß-induced PPARγ reduction. Nuclear translocation of HDAC3 in response to salusin-ß was significantly reversed by an IγBa inhibitor BAY 11-7085. Furthermore, IγBa-HDAC3 complex was present in the cytosol of VSMCs but interrupted after salusin-ß treatment. Conclusion: IγBa-HDAC3 pathway may contribute to salusin-ß-induced inhibition of PPARγ gene expression in VSMCs.

Transcript of protein kinase A knock-down modulates feeding behavior and neuropeptide Y gene expression in phenylpropanolamine-treated rats

2007 ◽  
Vol 31 (2) ◽  
pp. 306-314 ◽  
Author(s):  
Yih-Shou Hsieh ◽  
Shun-Fa Yang ◽  
Shu-Chen Chu ◽  
Dong-Yih Kuo
Keyword(s):  
Gene Expression ◽  
Protein Kinase ◽  
Neuropeptide Y ◽  
Protein Kinase A ◽  
Mrna Level ◽  
Camp Response Element Binding ◽  
Antisense Oligodeoxynucleotide ◽  
Mrna Levels ◽  
Knock Down ◽  
Kinase A

Neuropeptide Y (NPY) is an appetite-controlling neuromodulator that contributes to the appetite-suppressing effect of phenylpropanolamine (PPA). Aims of this study were to investigate whether protein kinase A (PKA) signaling is involved in regulating NPY gene expression and PPA-induced anorexia. Rats were given daily with PPA for 5 days. Changes in daily food intake and hypothalamic NPY, PKA, cAMP response element binding protein (CREB), and pro-opiomelanocortin (POMC) gene expression were measured and compared. To further determine if PKA was involved, intracerebroventricular infusions of antisense oligodeoxynucleotide were performed at 60 min before daily PPA treatment in freely moving rats. Results showed that daily PKA, CREB, and POMC expression were increased following PPA treatment, which showed a closely reverse relationship with alterations of decreased feeding behaviors and NPY mRNA levels. Results also showed that PKA knock-down could block PPA-induced anorexia as well as restore NPY mRNA level, indicating the involvement of PKA signaling in the regulation of NPY gene expression. It is suggested that hypothalamic PKA signaling may participate in the central regulation of PPA-mediated appetite suppression via the modulation of hypothalamic NPY gene expression. The present findings reveal that manipulations at the molecular level of PKA or cAMP may allow the development of therapeutic agents to improve the undesirable properties of PPA or other amphetamine-like anorectic drugs.

scholarly journals Leptin Rapidly Induces the Expression of Metabolic and Myokine Genes in C2C12 Muscle Cells to Regulate Nutrient Partition and Oxidation

2015 ◽  
Vol 35 (1) ◽  
pp. 92-103 ◽  
Author(s):  
Yuriy Nozhenko ◽  
Ana M. Rodríguez ◽  
Andreu Palou
Keyword(s):  
Time Course ◽  
Leptin Receptor ◽  
Uncoupling Protein ◽  
Muscle Cells ◽  
Pyruvate Dehydrogenase Kinase ◽  
C2c12 Myotubes ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Levels

Background: Skeletal muscle can experience pronounced metabolic adaptations in response to extrinsic stimuli, and expresses leptin receptor (OB-Rb). We aimed to further the understanding of leptin effects on muscle cells, by studying the expression of key energy metabolism genes in C2C12 myotubes. Methods: We performed a dose-time-dependent study with physiological concentrations of leptin: 5, 10 and 50ng/ml, for 0, 30', 3h, 6h, 12h and 24h, also monitoring time-course changes in non-treated cells. mRNA levels were analyzed by RT-qPCR and peroxisome proliferator activated receptor γ coactivator 1α (PGC1α) protein levels by western blot. Results: The most significant effects were observed with 50ng/ml leptin. In the short-term (30' and/or 3h), leptin significantly induced the expression of PGC1α, muscle carnitine palmitoyl transferase 1 (mCPT1), uncoupling protein 3 (UCP3), OB-Rb, Insulin receptor (InsR) and interleukins 6 and 15 (IL6, IL15). There was a decrease in mRNA levels of pyruvate dehydrogenase kinase 4 (PDK4) and mCPT1 in the long-term (24h). PGC1α protein levels were increased (24h). Conclusion: Leptin rapidly induces the expression of genes important for its own response and the control of metabolic fuels, with the rapid responses of the genes encoding the master regulator PGC1α, mCPT1, UCP3, PDK4 and the signaling secretory molecule IL6 particularly interesting.

scholarly journals Increasing Fat Deposition via Upregulates the Transcription of Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) in Native Crossbred Chicken

2020 ◽  
Author(s):  
Supanon Tunim ◽  
Yupin Phasuk ◽  
Samuel E. Aggrey ◽  
Monchai Duangjinda
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Intramuscular Fat ◽  
Abdominal Fat ◽  
Fat Deposition ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Chicken Breeds ◽  
Pparγ Expression ◽  
Pparγ Gene

Abstract Background: Crossbreeding using exotic breeds is usually employed to improve the growth characteristics of indigenous chickens. This mating not only provides growth but affect adversely to fat deposition as well. We studied the growth, abdominal, subcutaneous and intramuscular fat and mRNA expression of peroxisome proliferator-activated receptor (PPAR) α and PPARγ in adipose and muscle tissues of four chicken breeds [Chee breed (CH) (100% Thai native chicken), Kaimook e-san1 (KM1; 50% CH background), Kaimook e-san2 (KM2; 25% CH background), and broiler (BR)]. This study was aim to study role of PPARs on fat deposition in native crossbred chicken.Results: The BR chickens had higher abdominal fat than other breeds (P<0.05) and the KM2 had an abdominal fat percentage higher than KM1 and CH respectively (P<0.05). The intramuscular fat (IMF) of BR was greater than KM1 and CH (P<0.05). In adipose tissue, PPARα transcription expression was different among the chicken breeds. However, there were breed differences in PPARγ gene expression. Study of abdominal fat PPARγ gene expression showed the BR breed, KM1, and KM2 breed significantly greater (P<0.05) than CH. In 8 to 12 weeks of age, the result shows that the PPARγ expression of the CH breed is less than (P<0.05) KM2. The result of PPARs expression in muscle tissue was similar result in adipose tissue.Conclusion: Crossbreeding improved the growth of the Thai native breed, there was also a corresponding increase in carcass fatness. However, there appears to be a relationship between PPARγ expression and fat deposition traits. therefore, PPARγ activity plays a key role in lipid accumulation by up-regulation.

Abstract 1729: PPARγ Regulates ABCG1 Expression in Macrophages via LXR-Driven Dual Promoters

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Makoto Ayaori ◽  
Masatsune Ogura ◽  
Kazuhiro Nakaya ◽  
Tetsuya Hisada ◽  
Shun-ichi Takiguchi ◽  
...  
Keyword(s):  
Cholesterol Efflux ◽  
Density Lipoprotein ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Levels ◽  
Exon 1 ◽  
Dual Promoters ◽  
Sirna Knockdown

ATP binding cassette transporter G1 (ABCG1), which is expressed in macrophages, has been implicated in the efflux of cholesterol to high density lipoprotein. Peroxisome proliferator-activated receptor γ (PPARγ) has been reported to be involved in cholesterol efflux from macrophages, and increased expression of ABCG1 via liver receptor X (LXR)-dependent and independent pathways. However, the mechanisms by which ABCG1 expression is increased by PPARγ have not been fully characterized. We observed that pioglitazone, a PPARγ ligand, increases cholesterol efflux from THP-1 macrophages, as well as ABCG1 mRNA and protein levels. Treatment with actinomycin D abolished the inducible effect of pioglitazone on ABCG1, indicating that pioglitazone transcriptionally activated ABCG1 expression. To clarify how pioglitazone regulates ABCG1 expression, we investigated promoter activity using reporter constructs containing human ABCG1 promoter A and B (located upstream of exon 1 and 5, respectively), with or without mutated LXR-binding sites. The results indicated that pioglitazone activated both promoters in an LXR-dependent manner. We also observed that pioglitazone increased two major transcripts driven by promoter A and B using specific primers for each transcript. To determine whether PPARγ and LXRα were involved in these effects of pioglitazone, we performed siRNA-knockdown of PPARγ and LXRα in macrophages, which resulted in 75% and 91% decreases in PPARγ and LXRα mRNA levels, respectively. PPARγ and LXRα-knockdown, respectively, completely or partially abolished pioglitazone-induced ABCG1 expression. In conclusion, these results suggest that pioglitazone transcriptionally increased ABCG1 expression in macrophages by activating dual promoters in an LXR-dependent manner. Further studies are needed to assess LXR-independent mechanisms for the stimulatory effect of pioglitazone on ABCG1.

scholarly journals Tissue-specific induction of 17 beta-hydroxysteroid dehydrogenase type IV by peroxisome proliferator chemicals is dependent on the peroxisome proliferator-activated receptor alpha

1998 ◽  
Vol 158 (2) ◽  
pp. 237-246 ◽  
Author(s):  
LQ Fan ◽  
RC Cattley ◽  
JC Corton
Keyword(s):  
Hydroxysteroid Dehydrogenase ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Ppar Alpha ◽  
Peroxisome Proliferator Activated Receptor ◽  
Receptor Alpha ◽  
Protein Levels ◽  
Type Iv ◽  
Liver And Kidney ◽  
The Impact

The 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) family of proteins regulates the levels of the active 17 beta-hydroxy forms of sex steroids. The expression of 17 beta-HSD type IV is induced by peroxisome proliferator chemicals (PPC) in rat liver. In order to characterize more generally the impact of PPC on 17 beta-HSD expression, we determined (1) if expression of other members of the 17 beta-HSD family was coordinately induced by PPC exposure, (2) the tissues in which 17 beta-HSD was induced by PPC, and (3) whether the induction of 17 beta-HSD by PPC was dependent on the peroxisome proliferator-activated receptor alpha (PPAR alpha), the central mediator of PPC effects in the mouse liver. The mRNA levels of 17 beta-HSD I, II, and III were not altered in the liver, kidney, and testis or uterus of rats treated with PPC. The mRNA or 80 kDa a full-length protein levels of 17 beta-HSD IV were strongly induced in liver and kidney, but not induced in adrenals, brown fat, heart, testis, and uterus of rats treated with diverse PPC. In liver and kidneys from treated rats, additional proteins of 66 kDa, 56 kDa, and 32 kDa were also induced which reacted with the anti-17 beta-HSD IV antibodies and were most likely proteolytic fragments of 17 bega-HSD IV. Treatment of mice which lack a functional form of PPAR alpha with PPC, demonstrated that PPC-inducibility of 17 beta-HSD IV mRNA or the 80 kDa protein was dependent on PPAR alpha expression in liver and kidney. Our results demonstrate that 17 beta-HSD IV is induced by PPC through a PPAR alpha-dependent mechanism and support the hypothesis that exposure to PPC leads to alterations in sex steroid metabolism.

scholarly journals Sex Difference in Hepatic Peroxisome Proliferator-Activated Receptor α Expression: Influence of Pituitary and Gonadal Hormones

Endocrinology ◽  
2003 ◽  
Vol 144 (1) ◽  
pp. 101-109 ◽  
Author(s):  
Masoumeh Jalouli ◽  
Linda Carlsson ◽  
Caroline Améen ◽  
Daniel Lindén ◽  
Anna Ljungberg ◽  
...  
Keyword(s):  
Sex Difference ◽  
Gonadal Hormones ◽  
Female Rats ◽  
Male Rats ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Gh Treatment ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Levels ◽  
Secretory Pattern

Abstract Peroxisome proliferator-activated receptor (PPAR) α is a nuclear receptor that is mainly expressed in tissues with a high degree of fatty acid oxidation such as liver, heart, and skeletal muscle. Unsaturated fatty acids, their derivatives, and fibrates activate PPARα. Male rats are more responsive to fibrates than female rats. We therefore wanted to investigate if there is a sex difference in PPARα expression. Male rats had higher levels of hepatic PPARα mRNA and protein than female rats. Fasting increased hepatic PPARα mRNA levels to a similar degree in both sexes. Gonadectomy of male rats decreased PPARα mRNA expression to similar levels as in intact and gonadectomized female rats. Hypophysectomy increased hepatic PPARα mRNA and protein levels. The increase in PPARα mRNA after hypophysectomy was more pronounced in females than in males. GH treatment decreased PPARα mRNA and protein levels, but the sex-differentiated secretory pattern of GH does not determine the sex-differentiated expression of PPARα. The expression of PPARα mRNA in heart or soleus muscle was not influenced by gender, gonadectomy, hypophysectomy, or GH treatment. In summary, pituitary-dependent hormones specifically regulate hepatic PPARα expression. Sex hormones regulate the sex difference in hepatic PPARα levels, but not via the sexually dimorphic GH secretory pattern.

Thermogenically competent nonadrenergic recruitment in brown preadipocytes by a PPARγ agonist

2008 ◽  
Vol 295 (2) ◽  
pp. E287-E296 ◽  
Author(s):  
Natasa Petrovic ◽  
Irina G. Shabalina ◽  
James A. Timmons ◽  
Barbara Cannon ◽  
Jan Nedergaard
Keyword(s):  
Primary Cultures ◽  
Brown Adipocyte ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Sympathetic Stimulation ◽  
Promoting Effect ◽  
Brown Adipocytes ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pparγ Agonist ◽  
Brown Adipose

Most physiologically induced examples of recruitment of brown adipose tissue (BAT) occur as a consequence of chronic sympathetic stimulation (norepinephrine release within the tissue). However, in some physiological contexts (e.g., prenatal and prehibernation recruitment), this pathway is functionally contraindicated. Thus a nonsympathetically mediated mechanism of BAT recruitment must exist. Here we have tested whether a PPARγ activation pathway could competently recruit BAT, independently of sympathetic stimulation. We continuously treated primary cultures of mouse brown (pre)adipocytes with the potent peroxisome proliferator-activated receptor-γ (PPARγ) agonist rosiglitazone. In rosiglitazone-treated cultures, morphological signs of adipose differentiation and expression levels of the general adipogenic marker aP2 were manifested much earlier than in control cultures. Importantly, in the presence of the PPARγ agonist the brown adipocyte phenotype was significantly enhanced: UCP1 was expressed even in the absence of norepinephrine, and PPARα expression and norepinephrine-induced PGC-1α mRNA levels were significantly increased. However, the augmented levels of PPARα could not explain the brown-fat promoting effect of rosiglitazone, as this effect was still evident in PPARα-null cells. In continuously rosiglitazone-treated brown adipocytes, mitochondriogenesis, an essential part of BAT recruitment, was significantly enhanced. Most importantly, these mitochondria were capable of thermogenesis, as rosiglitazone-treated brown adipocytes responded to the addition of norepinephrine with a large increase in oxygen consumption. This thermogenic response was not observable in rosiglitazone-treated brown adipocytes originating from UCP1-ablated mice; hence, it was UCP1 dependent. Thus the PPARγ pathway represents an alternative, potent, and fully competent mechanism for BAT recruitment, which may be the cellular explanation for the enigmatic recruitment in prehibernation and prenatal states.

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