scholarly journals Trans-Cinnamaldehyde Alleviates Amyloid-Beta Pathogenesis via the SIRT1-PGC1α-PPARγ Pathway in 5XFAD Transgenic Mice

2020 ◽  
Vol 21 (12) ◽  
pp. 4492
Author(s):  
Jimin Do ◽  
Namkwon Kim ◽  
Seung Ho Jeon ◽  
Min Sung Gee ◽  
Yeon-Joo Ju ◽  
...  
Keyword(s):  
Memory Function ◽  
Amyloid Β ◽  
Significant Feature ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Cinnamon Extract ◽  
In Vivo Experiments ◽  
5Xfad Mice ◽  
Main Component

Abnormal amyloid-β (Aβ) accumulation is the most significant feature of Alzheimer’s disease (AD). Among the several secretases involved in the generation of Aβ, β-secretase (BACE1) is the first rate-limiting enzyme in Aβ production that can be utilized to prevent the development of Aβ-related pathologies. Cinnamon extract, used in traditional medicine, was shown to inhibit the aggregation of tau protein and Aβ aggregation. However, the effect of trans-cinnamaldehyde (TCA), the main component of cinnamon, on Aβ deposition is unknown. Five-month-old 5XFAD mice were treated with TCA for eight weeks. Seven-month-old 5XFAD mice were evaluated for cognitive and spatial memory function. Brain samples collected at the conclusion of the treatment were assessed by immunofluorescence and biochemical analyses. Additional in vivo experiments were conducted to elucidate the mechanisms underlying the effect of TCA in the role of Aβ deposition. TCA treatment led to improvements in cognitive impairment and reduced Aβ deposition in the brains of 5XFAD mice. Interestingly, the levels of BACE1 were decreased, whereas the mRNA and protein levels of three well-known regulators of BACE1, silent information regulator 1 (SIRT1), peroxisome proliferator-activated receptor γ (PPARγ) coactivator 1α (PGC1α), and PPARγ, were increased in TCA-treated 5XFAD mice. TCA led to an improvement in AD pathology by reducing BACE1 levels through the activation of the SIRT1-PGC1α-PPARγ pathway, suggesting that TCA might be a useful therapeutic approach in AD.

scholarly journals Phytohormone Abscisic Acid Improves Memory Impairment and Reduces Neuroinflammation in 5xFAD Mice by Upregulation of LanC-Like Protein 2

2020 ◽  
Vol 21 (22) ◽  
pp. 8425
Author(s):  
Seung Ho Jeon ◽  
Namkwon Kim ◽  
Yeon-Joo Ju ◽  
Min Sung Gee ◽  
Danbi Lee ◽  
...  
Keyword(s):  
Abscisic Acid ◽  
Memory Impairment ◽  
Amyloid Β ◽  
The Elderly ◽  
Peroxisome Proliferator ◽  
Chain Reaction ◽  
Peroxisome Proliferator Activated Receptor ◽  
Polymerase Chain ◽  
Anti Inflammatory ◽  
5Xfad Mice

Alzheimer’s disease (AD), a type of dementia, is the most common neurodegenerative disease in the elderly. Neuroinflammation caused by deposition of amyloid β (Aβ) is one of the most important pathological causes in AD. The isoprenoid phytohormone abscisic acid (ABA) has recently been found in mammals and was shown to be an endogenous hormone, acting in stress conditions. Although ABA has been associated with anti-inflammatory effects and reduced cognitive impairment in several studies, the mechanisms of ABA in AD has not been ascertained clearly. To investigate the clearance of Aβ and anti-inflammatory effects of ABA, we used quantitative real-time polymerase chain reaction and immunoassay. ABA treatment inhibited Aβ deposition and neuroinflammation, thus resulting in improvement of memory impairment in 5xFAD mice. Interestingly, these effects were not associated with activation of peroxisome proliferator-activated receptor gamma, well known as a molecular target of ABA, but related with modulation of the LanC-like protein 2 (LANCL2), known as a receptor of ABA. Taken together, our results indicate that ABA reduced Aβ deposition, neuroinflammation, and memory impairment, which is the most characteristic pathology of AD, via the upregulation of LANCL2. These data suggest that ABA might be a candidate for therapeutics for AD treatment.

scholarly journals The Effects of Brown Algae-Derived Monosaccharide L-Fucose on Lipid Metabolism in C57BL/6J Obese Mice

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3798
Author(s):  
Xiao Yuan ◽  
Tomohiko Nakao ◽  
Hina Satone ◽  
Kazuyuki Ohara ◽  
Yuri Kominami ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Public Health Problem ◽  
Mass Gain ◽  
Peroxisome Proliferator ◽  
Global Public Health ◽  
High Molecular Weight Adiponectin ◽  
Peroxisome Proliferator Activated Receptor ◽  
In Vivo Experiments ◽  
Calorie Diet

Obesity is a global public health problem and a risk factor for several metabolic disorders as well as cancer. In this study, we investigated the effects of L-fucose on lipid metabolism through chronic and acute in vivo experiments in mice. In the chronic test, mice were fed a high-calorie diet (HCD) containing 0.0001%, 0.001%, 0.01%, and 0.1% L-fucose for one month. The L-fucose supplementation inhibited body weight and visceral fat mass gain in HCD-fed mice. The results of the acute test showed that L-fucose increased the ratio of serum high molecular weight adiponectin and enhanced glucose and lipid catabolism. Furthermore, L-fucose also decreased the expression of adipogenic genes (peroxisome proliferator-activated receptor γ and cluster of differentiation 36). In conclusion, this study provides a new approach to combat obesity and the related diseases.

scholarly journals Adipocyte PHLPP2 inhibition prevents obesity-induced fatty liver

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.

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

BMC Cancer ◽  
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.

scholarly journals The Novel Role of PGC1α in Bone Metabolism

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.

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 Activation of Peroxisome Proliferator-Activated Receptor γ Does Not Inhibit IL-6 or TNF-α Responses of Macrophages to Lipopolysaccharide In Vitro or In Vivo

2000 ◽  
Vol 164 (2) ◽  
pp. 1046-1054 ◽  
Author(s):  
Rolf Thieringer ◽  
Judy E. Fenyk-Melody ◽  
Cheryl B. Le Grand ◽  
Beverly A. Shelton ◽  
Patricia A. Detmers ◽  
...  
Keyword(s):  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Tnf Α

Tartary buckwheat improves cognition and memory function in an in vivo amyloid-β-induced Alzheimer model

2013 ◽  
Vol 53 ◽  
pp. 105-111 ◽  
Author(s):  
Ji Yeon Choi ◽  
Eun Ju Cho ◽  
Hae Song Lee ◽  
Jeong Min Lee ◽  
Young-Ho Yoon ◽  
...  
Keyword(s):  
Memory Function ◽  
Amyloid Β ◽  
Tartary Buckwheat

scholarly journals Opposing Roles of Peroxisome Proliferator-activated Receptor α and Growth Hormone in the Regulation of CYP4A11 Expression in a Transgenic Mouse Model

2009 ◽  
Vol 284 (24) ◽  
pp. 16541-16552 ◽  
Author(s):  
Üzen Savas ◽  
Daniel E. W. Machemer ◽  
Mei-Hui Hsu ◽  
Pryce Gaynor ◽  
Jerome M. Lasker ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Hormone ◽  
Transgenic Mice ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Peroxisome Proliferator ◽  
Sexually Dimorphic ◽  
Peroxisome Proliferator Activated Receptor ◽  
Liver And Kidney

CYP4A11 transgenic mice (CYP4A11 Tg) were generated to examine in vivo regulation of the human CYP4A11 gene. Expression of CYP4A11 in mice yields liver and kidney P450 4A11 levels similar to those found in the corresponding human tissues and leads to an increased microsomal capacity for ω-hydroxylation of lauric acid. Fasted CYP4A11 Tg mice exhibit 2–3-fold increases in hepatic CYP4A11 mRNA and protein, and this response is absent in peroxisome proliferator-activated receptor α (PPARα) null mice. Dietary administration of either of the PPARα agonists, fenofibrate or clofibric acid, increases hepatic and renal CYP4A11 levels by 2–3-fold, and these responses were also abrogated in PPARα null mice. Basal liver CYP4A11 levels are reduced differentially in PPARα−/− females (>95%) and males (<50%) compared with PPARα−/+ mice. Quantitative and temporal differences in growth hormone secretion are known to alter hepatic lipid metabolism and to underlie sexually dimorphic gene expression, respectively. Continuous infusion of low levels of growth hormone reduced CYP4A11 expression by 50% in PPARα-proficient male and female transgenic mice. A larger decrease was observed for the expression of CYP4A11 in PPARα−/− CYP4A11 Tg male mice to levels similar to that of female PPARα-deficient mice. These results suggest that PPARα contributes to the maintenance of basal CYP4A11 expression and mediates CYP4A11 induction in response to fibrates or fasting. In contrast, increased exposure to growth hormone down-regulates CYP4A11 expression in liver.

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