In Vivo Effects of Lipopolysaccharide on Peroxisome Proliferator-Activated Receptor Expression in Juvenile Gilthead Seabream (Sparus Aurata)

Omega-3 fatty acids, which are abundant in fish oil, improve the prognosis of several chronic inflammatory diseases although the mechanism for such effects remains unclear. These fatty acids, such as eicosapentaenoic acid (EPA), are highly polyunsaturated and readily undergo oxidation. We show that oxidized, but not native unoxidized, EPA significantly inhibited human neutrophil and monocyte adhesion to endothelial cells in vitro by inhibiting endothelial adhesion receptor expression. In transcriptional coactivation assays, oxidized EPA potently activated the peroxisome proliferator-activated receptor α (PPARα), a member of the nuclear receptor family. In vivo, oxidized, but not native, EPA markedly reduced leukocyte rolling and adhesion to venular endothelium of lipopolysaccharide (LPS)–treated mice. This occurred via a PPARα-dependent mechanism because oxidized EPA had no such effect in LPS-treated PPARα-deficient mice. Therefore, the beneficial effects of omega-3 fatty acids may be explained by a PPARα-mediated anti-inflammatory effect of oxidized EPA.

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Peroxisome proliferator-activated receptor (PPAR)-γ ligand inhibits the progression of pancreatic fibrosis in vivo and profibrogenic action in pancreatic myofibroblast

Gastroenterology ◽

10.1016/s0016-5085(01)80545-x ◽

2001 ◽

Vol 120 (5) ◽

pp. A111-A111

Author(s):

K SHIMIZU ◽

S HISADA ◽

K SHIRATORI ◽

M KOBAYASHI ◽

N HAYASHI

Keyword(s):

Pancreatic Fibrosis ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Ppar Γ

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Adipocyte PHLPP2 inhibition prevents obesity-induced fatty liver

Nature Communications ◽

10.1038/s41467-021-22106-2 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

KyeongJin Kim ◽

Jin Ku Kang ◽

Young Hoon Jung ◽

Sang Bae Lee ◽

Raffaela Rametta ◽

...

Keyword(s):

Fatty Liver ◽

Whole Body ◽

Acid Oxidation ◽

Chow Diet ◽

Peroxisome Proliferator ◽

Obese Mice ◽

Ph Domain ◽

Peroxisome Proliferator Activated Receptor

AbstractIncreased adiposity confers risk for systemic insulin resistance and type 2 diabetes (T2D), but mechanisms underlying this pathogenic inter-organ crosstalk are incompletely understood. We find PHLPP2 (PH domain and leucine rich repeat protein phosphatase 2), recently identified as the Akt Ser473 phosphatase, to be increased in adipocytes from obese mice. To identify the functional consequence of increased adipocyte PHLPP2 in obese mice, we generated adipocyte-specific PHLPP2 knockout (A-PHLPP2) mice. A-PHLPP2 mice show normal adiposity and glucose metabolism when fed a normal chow diet, but reduced adiposity and improved whole-body glucose tolerance as compared to Cre- controls with high-fat diet (HFD) feeding. Notably, HFD-fed A-PHLPP2 mice show increased HSL phosphorylation, leading to increased lipolysis in vitro and in vivo. Mobilized adipocyte fatty acids are oxidized, leading to increased peroxisome proliferator-activated receptor alpha (PPARα)-dependent adiponectin secretion, which in turn increases hepatic fatty acid oxidation to ameliorate obesity-induced fatty liver. Consistently, adipose PHLPP2 expression is negatively correlated with serum adiponectin levels in obese humans. Overall, these data implicate an adipocyte PHLPP2-HSL-PPARα signaling axis to regulate systemic glucose and lipid homeostasis, and suggest that excess adipocyte PHLPP2 explains decreased adiponectin secretion and downstream metabolic consequence in obesity.

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The lipid-lowering drug fenofibrate combined with si-HOTAIR can effectively inhibit the proliferation of gliomas

BMC Cancer ◽

10.1186/s12885-021-08417-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Wei Zhu ◽

Hongyang Zhao ◽

Fenfen Xu ◽

Bin Huang ◽

Xiaojing Dai ◽

...

Keyword(s):

Noncoding Rna ◽

Glioma Cells ◽

Lipid Lowering ◽

Fibric Acid Derivative ◽

Peroxisome Proliferator ◽

Glioma Invasion ◽

Peroxisome Proliferator Activated Receptor ◽

Lncrna Hotair

Abstract Background Fenofibrate is a fibric acid derivative known to have a lipid-lowering effect. Although fenofibrate-induced peroxisome proliferator-activated receptor alpha (PPARα) transcription activation has been shown to play an important role in the malignant progression of gliomas, the underlying mechanisms are poorly understood. Methods In this study, we analyzed TCGA database and found that there was a significant negative correlation between the long noncoding RNA (lncRNA) HOTAIR and PPARα. Then, we explored the molecular mechanism by which lncRNA HOTAIR regulates PPARα in cell lines in vitro and in a nude mouse glioma model in vivo and explored the effect of the combined application of HOTAIR knockdown and fenofibrate treatment on glioma invasion. Results For the first time, it was shown that after knockdown of the expression of HOTAIR in gliomas, the expression of PPARα was significantly upregulated, and the invasion and proliferation ability of gliomas were obviously inhibited. Then, glioma cells were treated with both the PPARα agonist fenofibrate and si-HOTAIR, and the results showed that the proliferation and invasion of glioma cells were significantly inhibited. Conclusions Our results suggest that HOTAIR can negatively regulate the expression of PPARα and that the combination of fenofibrate and si-HOTAIR treatment can significantly inhibit the progression of gliomas. This introduces new ideas for the treatment of gliomas.

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The Novel Role of PGC1α in Bone Metabolism

International Journal of Molecular Sciences ◽

10.3390/ijms22094670 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4670

Author(s):

Cinzia Buccoliero ◽

Manuela Dicarlo ◽

Patrizia Pignataro ◽

Francesco Gaccione ◽

Silvia Colucci ◽

...

Keyword(s):

Bone Metabolism ◽

Osteoblastic Differentiation ◽

In Vivo Studies ◽

Peroxisome Proliferator ◽

Sirtuin 3 ◽

Peroxisome Proliferator Activated Receptor ◽

Increased Risk

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) is a protein that promotes transcription of numerous genes, particularly those responsible for the regulation of mitochondrial biogenesis. Evidence for a key role of PGC1α in bone metabolism is very recent. In vivo studies showed that PGC1α deletion negatively affects cortical thickness, trabecular organization and resistance to flexion, resulting in increased risk of fracture. Furthermore, in a mouse model of bone disease, PGC1α activation stimulates osteoblastic gene expression and inhibits atrogene transcription. PGC1α overexpression positively affects the activity of Sirtuin 3, a mitochondrial nicotinammide adenina dinucleotide (NAD)-dependent deacetylase, on osteoblastic differentiation. In vitro, PGC1α overexpression prevents the reduction of mitochondrial density, membrane potential and alkaline phosphatase activity caused by Sirtuin 3 knockdown in osteoblasts. Moreover, PGC1α influences the commitment of skeletal stem cells towards an osteogenic lineage, while negatively affects marrow adipose tissue accumulation. In this review, we will focus on recent findings about PGC1α action on bone metabolism, in vivo and in vitro, and in pathologies that cause bone loss, such as osteoporosis and type 2 diabetes.

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

Molecular and Cellular Biology ◽

10.1128/mcb.00181-17 ◽

2017 ◽

Vol 38 (1) ◽

Cited By ~ 10

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.

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