scholarly journals Curcumin Relieves Chronic Unpredictable Mild Stress-Induced Depression-Like Behavior through the PGC-1α/FNDC5/BDNF Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Yanqin Wu ◽  
Fusheng Sun ◽  
Yujin Guo ◽  
Yumao Zhang ◽  
Li Li ◽  
...  
Keyword(s):  
Therapeutic Effects ◽  
Peroxisome Proliferator ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Peroxisome Proliferator Activated Receptor ◽  
Beneficial Effects ◽  
Regulatory Effects ◽  
Fibronectin Type Iii Domain ◽  
Bdnf Pathway

Background and Aim. Increasing evidence suggests that the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α)/fibronectin type III domain-containing 5 (FNDC5)/brain-derived neurotrophic factor (BDNF) pathway might be critical for neuroprotection. Our present study is aimed at investigating the antidepressant-like effects of curcumin (CUR) in a chronic unpredictable mild stress- (CUMS-) induced depression rat model and explore whether the PGC-1α/FNDC5/BDNF pathway is the major driving force behind the therapeutic effects of CUR. Methods. All rats were randomly divided into four groups, namely, control, CUMS, CUMS + CUR , and CUMS + CUR + SR 18292 (PGC-1α inhibitor). Behavioral tests were conducted to assess the antidepressant-like effects of CUR. The expressions of PGC-1α, estrogen-related receptor alpha (ERRα), FNDC5, and BDNF were determined to investigate the regulatory effects of CUR on the PGC-1α/FNDC5/BDNF pathway. The PGC-1α inhibitor SR18292 was used to explore the role of PGC-1α in the induction of BDNF by CUR. Results. Daily gavage of 100 mg/kg CUR successfully attenuated the abnormal behaviors induced by CUMS and effectively prevented CUMS-induced reduction of PGC-1α, ERRα, FNDC5, and BDNF expressions. CUR also enhanced PGC-1α and ERRα translocation from cytoplasm to nucleus. Furthermore, we found that CUR supplementation effectively promoted neurocyte proliferation and suppressed neuronal apoptosis induced by CUMS. Of note, the PGC-1α inhibitor SR18292 remarkably reversed the beneficial effects of CUR on depressed rats, indicating an important role of PGC-1α in the antidepressant-like effects of CUR. Conclusion. Collectively, our data evaluating the neuroprotective action of CUR in the CUMS rats highlights the involvement of the PGC-1α/FNDC5/BDNF pathway in the antidepressant-like effects of CUR.

scholarly journals From Exercise to Cognitive Performance: Role of Irisin

2021 ◽  
Vol 11 (15) ◽  
pp. 7120
Author(s):  
Mirko Pesce ◽  
Irene La Fratta ◽  
Teresa Paolucci ◽  
Alfredo Grilli ◽  
Antonia Patruno ◽  
...  
Keyword(s):  
The Elderly ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Beneficial Effects ◽  
General Exercise ◽  
Fibronectin Type Iii ◽  
Exercise Induced ◽  
Fibronectin Type Iii Domain ◽  
The Brain

The beneficial effects of exercise on the brain are well known. In general, exercise offers an effective way to improve cognitive function in all ages, particularly in the elderly, who are considered the most vulnerable to neurodegenerative disorders. In this regard, myokines, hormones secreted by muscle in response to exercise, have recently gained attention as beneficial mediators. Irisin is a novel exercise-induced myokine, that modulates several bodily processes, such as glucose homeostasis, and reduces systemic inflammation. Irisin is cleaved from fibronectin type III domain containing 5 (FNDC5), a transmembrane precursor protein expressed in muscle under the control of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). The FNDC5/irisin system is also expressed in the hippocampus, where it stimulates the expression of the neurotrophin brain-derived neurotrophic factor in this area that is associated with learning and memory. In this review, we aimed to discuss the role of irisin as a key mediator of the beneficial effects of exercise on synaptic plasticity and memory in the elderly, suggesting its roles within the main promoters of the beneficial effects of exercise on the brain.

scholarly journals Cyclin G2 Regulates Adipogenesis through PPARγ Coactivation

Endocrinology ◽  
2010 ◽  
Vol 151 (11) ◽  
pp. 5247-5254 ◽  
Author(s):  
Victor Aguilar ◽  
Jean-Sébastien Annicotte ◽  
Xavier Escote ◽  
Joan Vendrell ◽  
Dominique Langin ◽  
...  
Keyword(s):  
Adipocyte Differentiation ◽  
Luciferase Reporter ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Cell Cycle Regulators ◽  
Luciferase Reporter Gene ◽  
Peroxisome Proliferator Activated Receptor ◽  
Cyclin G2 ◽  
Regulatory Effects

Cell cycle regulators such as cyclins, cyclin-dependent kinases, or retinoblastoma protein play important roles in the differentiation of adipocytes. In the present paper, we investigated the role of cyclin G2 as a positive regulator of adipogenesis. Cyclin G2 is an unconventional cyclin which expression is up-regulated during growth inhibition or apoptosis. Using the 3T3-F442A cell line, we observed an up-regulation of cyclin G2 expression at protein and mRNA levels throughout the process of cell differentiation, with a further induction of adipogenesis when the protein is transiently overexpressed. We show here that the positive regulatory effects of cyclin G2 in adipocyte differentiation are mediated by direct binding of cyclin G2 to peroxisome proliferator-activated receptor γ (PPARγ), the key regulator of adipocyte differentiation. The role of cyclin G2 as a novel PPARγ coactivator was further demonstrated by chromatin immunoprecipitation assays, which showed that the protein is present in the PPARγ-responsive element of the promoter of aP2, which is a PPARγ target gene. Luciferase reporter gene assays, showed that cyclin G2 positively regulates the transcriptional activity of PPARγ. The role of cyclin G2 in adipogenesis is further underscored by its increased expression in mice fed a high-fat diet. Taken together, our results demonstrate a novel role for cyclin G2 in the regulation of adipogenesis.

scholarly journals PPARγin Inflammatory Bowel Disease

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Vito Annese ◽  
Francesca Rogai ◽  
Alessia Settesoldi ◽  
Siro Bagnoli
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Potential Role ◽  
Intestinal Inflammation ◽  
Experimental Colitis ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Beneficial Effects ◽  
Inflammatory Bowel

Peroxisome proliferator-activated receptor gamma (PPARγ) is member of a family of nuclear receptors that interacts with nuclear proteins acting as coactivators and corepressors. The colon is a major tissue which expresses PPARγin epithelial cells and, to a lesser degree, in macrophages and lymphocytes and plays a role in the regulation of intestinal inflammation. Indeed, both natural and synthetic PPARγligands have beneficial effects in different models of experimental colitis, with possible implication in the therapy of inflammatory bowel disease (IBD). This paper will specifically focus on potential role of PPARγin the predisposition and physiopathology of IBD and will analyze its possible role in medical therapy.

scholarly journals The Role of PPARγ Ligands in Breast Cancer: From Basic Research to Clinical Studies

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2623
Author(s):  
Giuseppina Augimeri ◽  
Cinzia Giordano ◽  
Luca Gelsomino ◽  
Pierluigi Plastina ◽  
Ines Barone ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Studies ◽  
Molecular Mechanisms ◽  
Basic Research ◽  
Therapeutic Effects ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Natural And Synthetic

Peroxisome proliferator-activated receptor gamma (PPARγ), belonging to the nuclear receptor superfamily, is a ligand-dependent transcription factor involved in a variety of pathophysiological conditions such as inflammation, metabolic disorders, cardiovascular disease, and cancers. In this latter context, PPARγ is expressed in many tumors including breast cancer, and its function upon binding of ligands has been linked to the tumor development, progression, and metastasis. Over the last decade, much research has focused on the potential of natural agonists for PPARγ including fatty acids and prostanoids that act as weak ligands compared to the strong and synthetic PPARγ agonists such as thiazolidinedione drugs. Both natural and synthetic compounds have been implicated in the negative regulation of breast cancer growth and progression. The aim of the present review is to summarize the role of PPARγ activation in breast cancer focusing on the underlying cellular and molecular mechanisms involved in the regulation of cell proliferation, cell cycle, and cell death, in the modulation of motility and invasion as well as in the cross-talk with other different signaling pathways. Besides, we also provide an overview of the in vivo breast cancer models and clinical studies. The therapeutic effects of natural and synthetic PPARγ ligands, as antineoplastic agents, represent a fascinating and clinically a potential translatable area of research with regards to the battle against cancer.

scholarly journals FNDC5/Irisin System in Neuroinflammation and Neurodegenerative Diseases: Update and Novel Perspective

2021 ◽  
Vol 22 (4) ◽  
pp. 1605
Author(s):  
Patrizia Pignataro ◽  
Manuela Dicarlo ◽  
Roberta Zerlotin ◽  
Chiara Zecca ◽  
Maria Teresa Dell’Abate ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Hippocampal Neurons ◽  
Peroxisome Proliferator ◽  
Bdnf Expression ◽  
Peroxisome Proliferator Activated Receptor ◽  
Beneficial Effects ◽  
Positive Effects ◽  
Fibronectin Type Iii ◽  
System Functioning ◽  
Fibronectin Type Iii Domain

Irisin, the circulating peptide originating from fibronectin type III domain-containing protein 5 (FNDC5), is mainly expressed by muscle fibers under peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) control during exercise. In addition to several beneficial effects on health, physical activity positively affects nervous system functioning, particularly the hippocampus, resulting in amelioration of cognition impairments. Recently, FNDC5/irisin detection in hippocampal neurons and the presence of irisin in the cerebrospinal fluid opened a new intriguing chapter in irisin history. Interestingly, in the hippocampus of mice, exercise increases FNDC5 levels and upregulates brain-derived neurotrophic factor (BDNF) expression. BDNF, displaying neuroprotection and anti-inflammatory effects, is mainly produced by microglia and astrocytes. In this review, we discuss how these glial cells can morphologically and functionally switch during neuroinflammation by modulating the expression of a plethora of neuroprotective or neurotoxic factors. We also focus on studies investigating the irisin role in neurodegenerative diseases (ND). The emerging involvement of irisin as a mediator of the multiple positive effects of exercise on the brain needs further studies to better deepen this issue and the potential use in therapeutic approaches for neuroinflammation and ND.

scholarly journals Role of PPARαand Its Agonist in Renal Diseases

PPAR Research ◽  
2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Ching-Feng Cheng ◽  
Hsi-Hsien Chen ◽  
Heng Lin
Keyword(s):  
Kidney Diseases ◽  
Renal Diseases ◽  
Therapeutic Effects ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ligand Selectivity ◽  
Treatment Of Diabetes ◽  
Hypolipidemic Drugs ◽  
Anti Inflammation

Peroxisome proliferator-activated receptor (PPAR)-α, a member of a large nuclear receptor superfamily, plays a major role in the regulation of lipid metabolism. Recently, PPARαactivation has been shown to confer additional benefits on endothelial function, kidney function, and anti-inflammation, suggesting that PPARαagonists may be good candidates for treating acute renal failure. In clinical application, PPAR-αactivators, such as hypolipidemic drugs in fibric acid class, were proven to have therapeutic effects on metabolic syndrome and cardiovascular disease. This paper focuses on signaling pathways, ligand selectivity, and physio-pathological roles of PPARαin kidney diseases and the therapeutic utility of PPARαmodulators in the treatment of diabetes and inflammation-induced nephropathy. Implication of new and more potent PPAR-αactivators could provide important insights into the overall benefits of activating PPAR-αclinically for the treatment of dyslipidemia and the prevention of diabetic or inflammation-induced nephropathy in the future.

scholarly journals Curcumin relieves CUMS-induced depressive-like behaviors through PGC-1α/FNDC5/BDNF pathway

2021 ◽  
Author(s):  
Yanqin Wu ◽  
Fusheng Sun ◽  
Yujin Guo ◽  
Yumao Zhang ◽  
Li Li ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Curcuma Longa ◽  
Primary Component ◽  
Antidepressant Effect ◽  
Peroxisome Proliferator ◽  
Mild Stress ◽  
Sprague Dawley ◽  
Nissl Staining ◽  
Peroxisome Proliferator Activated Receptor ◽  
Bdnf Pathway

Abstract Background Curcumin (CUR), a primary component extracted from the Chinese medicine Curcuma longa, has been suggested to be effective in treating symptoms of a variety of neuropsychiatric disorders including depression. However, the underlying mechanism of CUR’s antidepressant properties remains largely unknown. In this study, the antidepressant effect and its mechanism of CUR were investigated. Methods In this study, the chronic unpredictable mild stress- (CUMS-) induced depression model was employed to investigate the antidepressant effect of CUR. The depressive-like state was evaluated by the behavioral tests. On the day of the sacrifice, blood samples and the hippocampus of Sprague Dawley (SD) rats were collected for the following analysis. The proteins were investigated by Western blotting analysis and immunofluorescence analysis. The mRNA expression was analyzed by quantitative real-time PCR. Cell proliferation and apoptosis was determined with Brdu cell proliferation assay and Nissl staining assay. Results After stress exposure for six weeks, the CUMS rats showed depressive-like behaviors, and the administration of CUR successfully attenuated the depressive-like behaviors in CUMS-treated rats. Additionally, CUR effectively increased the expression of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), fibronectin type III domain-containing 5 (FNDC5), and brain-derived neurotrophic factor (BDNF). The CUR also stimulated the transcription of PGC-1α and estrogen-related receptor alpha (ERRα), enhanced PGC-1α and ERRα translocation from cytoplasm to nucleus, thus activating the PGC-1α/FNDC5/BDNF pathway. Furthermore, we found the supplementation of CUR effectively promoted neurocyte proliferation and suppressed neural apoptosis induced by CUMS. Conclusions Collectively, the study revealed that CUR exerts antidepressant-like effect through the activation of the PGC-1α/FNDC5/BDNF pathway.

scholarly journals Effects of Baicalin on the ATP Levels in the Prefrontal Cortex in Mice Exposed to Chronic Unpredictable Mild Stress

2021 ◽  
Author(s):  
Shuai-fei Lu ◽  
Xiao-hui Jin ◽  
Lei-lei Zhu ◽  
Ji-duo Shen ◽  
Ming Bai ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Mitochondrial Function ◽  
Mental Disease ◽  
Sirtuin 1 ◽  
Antidepressant Effect ◽  
Peroxisome Proliferator ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Mice Model ◽  
Peroxisome Proliferator Activated Receptor

Abstract Depression is gradually becoming a primary mental disease threatening human health. It is urgent to clarify the pathogenesis of depression and find new effective natural antidepressants. This study aimed to investigate the antidepressant effects of baicalin and explore its potential mechanism in a mice model of depression induced by chronic unpredictable mild stress (CUMS). Following a 6-weeks CUMS exposure, the CUMS mice were treated with baicalin (10 mg/kg) and fluoxetine (20 mg/kg) for 4 weeks by oral gavage. The sucrose preference test (SPT) and forced swimming test (FST) were performed to evaluate the depression-like behaviors, and the levels of adenosine triphosphate (ATP) in the prefrontal cortex were detected. Moreover, the gene expression and enzyme activities related to the production of ATP and mitochondrial function were detected. The results indicated that the depression-like behaviors of mice induced by CUMS were improved by baicalin and fluoxetine. In addition, baicalin significantly increased the ATP content, the mRNA expression of hexokinase (HK), pyruvate dehydrogenase alpha (PDHα), isocitrate dehydrogenase (IDH), peroxisome proliferator-activated receptor γ coactivator-1alpha (PGC1α), and sirtuin 1 (SIRT1) in the prefrontal cortex. Furthermore, baicalin also increased the activity of respiratory chain complex I, V, and the level of mitochondrial membrane potential (MMP). In conclusion, the present results suggested that the antidepressant effect of baicalin may be partly mediated by accelerating the process of glycolysis and tricarboxylic acid (TCA) and improving the mitochondrial function to enhance the ATP level in the brain.

The emerging role of COX-2, 15-LOX, and PPARγ in metabolic diseases and cancer: An introduction to novel multi-target directed ligands (MTDLs)

2020 ◽  
Vol 27 ◽  
Author(s):  
Rana A. Alaaeddine ◽  
Perihan A. Elzahhar ◽  
Ibrahim AlZaim ◽  
Wassim Abou-Kheir ◽  
Ahmed S.F. Belal ◽  
...  
Keyword(s):  
Metabolic Diseases ◽  
Biological Effects ◽  
Arachidonic Acid Metabolism ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Cellular Targets ◽  
Design And Synthesis ◽  
Early Results ◽  
Cox 2

: Emerging evidence supports an intertwining framework for the involvement of different inflammatory pathways in a common pathological background for a number of disorders. Of importance are pathways involving arachidonic acid metabolism by cyclooxygenase-2 (COX-2) and 15-lipoxygenase (15-LOX). Both enzyme activities and their products are implicated in a range of pathophysiological processes encompassing metabolic impairment leading to adipose inflammation and the subsequent vascular and neurological disorders, in addition to various pro-and anti-tumorigenic effects. A further layer of complexity is encountered by the disparate, and often reciprocal, modulatory effect COX-2 and 15-LOX activities and metabolites exert on each other or on other cellular targets, the most prominent of which is peroxisome proliferator-activated receptor gamma (PPARγ). Thus, effective therapeutic intervention with such multifaceted disorders requires the simultaneous modulation of more than one target. Here, we describe the role of COX-2, 15-LOX, and PPARγ in cancer and complications of metabolic disorders, highlight the value of designing multi-target directed ligands (MTDLs) modifying their activity, and summarize the available literature regarding the rationale and feasibility of design and synthesis of these ligands together with their known biological effects. We speculate on the potential impact of MTDLs in these disorders as well as emphasize the need for structured future effort to translate these early results facilitating the adoption of these, and similar, molecules in clinical research.

scholarly journals Beneficial Effects of Akkermansia muciniphila Are Not Associated with Major Changes in the Circulating Endocannabinoidome but Linked to Higher Mono-Palmitoyl-Glycerol Levels as New PPARα Agonists

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 185
Author(s):  
Clara Depommier ◽  
Rosa Maria Vitale ◽  
Fabio Arturo Iannotti ◽  
Cristoforo Silvestri ◽  
Nicolas Flamand ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Univariate Analysis ◽  
Metabolic Effects ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Akkermansia Muciniphila ◽  
Beneficial Effects ◽  
Daily Ingestion ◽  
Before And After ◽  
Palmitoyl Glycerol

Akkermansia muciniphila is considered as one of the next-generation beneficial bacteria in the context of obesity and associated metabolic disorders. Although a first proof-of-concept of its beneficial effects has been established in the context of metabolic syndrome in humans, mechanisms are not yet fully understood. This study aimed at deciphering whether the bacterium exerts its beneficial properties through the modulation of the endocannabinoidome (eCBome). Circulating levels of 25 endogenous endocannabinoid-related lipids were quantified by liquid chromatography with tandem mass spectrometry (LC-MS/MS) in the plasma of overweight or obese individuals before and after a 3 months intervention consisting of the daily ingestion of either alive or pasteurized A. muciniphila. Results from multivariate analyses suggested that the beneficial effects of A. muciniphila were not linked to an overall modification of the eCBome. However, subsequent univariate analysis showed that the decrease in 1-Palmitoyl-glycerol (1-PG) and 2-Palmitoyl-glycerol (2-PG), two eCBome lipids, observed in the placebo group was significantly counteracted by the alive bacterium, and to a lower extent by the pasteurized form. We also discovered that 1- and 2-PG are endogenous activators of peroxisome proliferator-activated receptor alpha (PPARα). We hypothesize that PPARα activation by mono-palmitoyl-glycerols may underlie part of the beneficial metabolic effects induced by A. muciniphila in human metabolic syndrome.

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