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.

scholarly journals Peroxisome proliferator-activated receptor gamma agonists in renal disease

2006 ◽  
Vol 154 (5) ◽  
pp. 613-621 ◽  
Author(s):  
Pedro Iglesias ◽  
Juan J Díez
Keyword(s):  
Type 2 Diabetes ◽  
Renal Function ◽  
Experimental Studies ◽  
Metabolic Effects ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Beneficial Effects ◽  
Patients With Diabetes ◽  
Pparγ Agonists

Type 2 diabetes is a well recognised cause of chronic renal failure (CRF). Only few oral antidiabetic drugs can be used for treating type 2 diabetes in patients with CRF. Among them are repaglinide, a rapid-acting prandial insulin releaser, and peroxisome proliferator-activated receptor gamma (PPARγ) agonists, such as rosiglitazone and pioglitazone. These compounds are metabolised in the liver, therefore accumulation of the drug and the risk of severe and prolonged hypoglycaemia are minimised. PPARγ receptors are expressed in many tissues including the kidney. Recently, numerous healthful effects of PPARγ agonists on several aspects related to renal function have been increasingly reported. These drugs have shown to possess many advantageous anti-inflammatory, haemodynamic, vascular and metabolic effects. In the present paper we have reviewed the more recent experimental studies that evaluated these potential beneficial effects of PPARγ agonists on renal function and revised the results of their utilisation in patients with different degrees of renal impairment, in dialysis patients, and in patients with diabetes mellitus after kidney transplantation. Finally, tolerability and safety profile of PPARγ agonists in patients with reduced glomerular filtration rate are also analysed.

Novel Hypolipidaemic Drugs: Mechanisms of Action and Main Metabolic Effects

2019 ◽  
Vol 17 (4) ◽  
pp. 332-340 ◽  
Author(s):  
Theodosios D. Filippatos ◽  
Angelos Liontos ◽  
Eliza C. Christopoulou ◽  
Moses S. Elisaf
Keyword(s):  
Lipid Metabolism ◽  
Low Density Lipoprotein ◽  
Lipid Synthesis ◽  
Density Lipoprotein ◽  
Metabolic Effects ◽  
Infusion Therapy ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Beneficial Effects ◽  
Early Phase Clinical Trials

Over the last 3 decades, hypolipidaemic treatment has significantly reduced both Cardiovascular (CV) risk and events, with statins being the cornerstone of this achievement. Nevertheless, residual CV risk and unmet goals in hypolipidaemic treatment make novel options necessary. Recently marketed monoclonal antibodies against proprotein convertase subtilisin/kexin type 9 (PCSK9) have shown the way towards innovation, while other ways of PCSK9 inhibition like small interfering RNA (Inclisiran) are already being tested. Other effective and well tolerated drugs affect known paths of lipid synthesis and metabolism, such as bempedoic acid blocking acetyl-coenzyme A synthesis at a different level than statins, pemafibrate selectively acting on peroxisome proliferator-activated receptor (PPAR)- alpha receptors and oligonucleotides against apolipoprotein (a). Additionally, other novel hypolipidaemic drugs are in early phase clinical trials, such as the inhibitors of apolipoprotein C-III, which is located on triglyceride (TG)-rich lipoproteins, or the inhibitors of angiopoietin-like 3 (ANGPTL3), which plays a key role in lipid metabolism, aiming to beneficial effects on TG levels and glucose metabolism. Among others, gene therapy substituting the loss of essential enzymes is already used for Lipoprotein Lipase (LPL) deficiency in autosomal chylomicronaemia and is expected to eliminate the lack of Low- Density Lipoprotein (LDL) receptors in patients with homozygous familial hypercholesterolaemia. Experimental data of High-Density Lipoprotein (HDL) mimetics infusion therapy have shown a beneficial effect on atherosclerotic plaques. Thus, many novel hypolipidaemic drugs targeting different aspects of lipid metabolism are being investigated, although they need to be assessed in large trials to prove their CV benefit and safety.

scholarly journals GDF15 Mediates the Metabolic Effects of PPARβ/δ by Activating AMPK

2020 ◽  
Author(s):  
David Aguilar-Recarte ◽  
Emma Barroso ◽  
Javier Pizarro-Delgado ◽  
Lucía Peña ◽  
Maria Ruart ◽  
...  
Keyword(s):  
Neutralizing Antibody ◽  
Metabolic Effects ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Ampk Activation ◽  
Peroxisome Proliferator Activated Receptor ◽  
Growth Differentiation Factor 15 ◽  
Beneficial Effects ◽  
Glucose And Lipid Metabolism ◽  
Amp Activated Protein Kinase

Abstract Peroxisome proliferator-activated receptor β/δ(PPARβ/δ) activates AMP-activated protein kinase (AMPK) and plays a crucial role in glucose and lipid metabolism. Here, we examined whether the beneficial effects of PPARβ/δ activation depended on growth differentiation factor 15 (GDF15), a stress response cytokine that regulates energy metabolism. Pharmacological PPARβ/δ activation increased GDF15 levels and ameliorated glucose intolerance, fatty acid oxidation, endoplasmic reticulum stress, inflammation and activated AMPK in HFD-fed mice, whereas these effects were abrogated by the injection of a GDF15 neutralizing antibody and in Gdf15-/- mice. The AMPK-p53 pathway was involved in the PPARβ/δ-mediated increase in GDF15, which in turn activated again AMPK. Finally, Gdf15-/- mice showed reduced AMPK activation in skeletal muscle, whereas GDF15 administration resulted in AMPK activation in this organ. Collectively, these data reveal a novel mechanism by which PPARβ/δ activation increases the levels of GDF15 via AMPK and p53, which in turn mediates the metabolic effects of PPARβ/δ by sustaining AMPK activation.

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.

Abstract 12555: The Dual PPAR-α/γ Agonist Aleglitazar Enhances Arteriogenesis, Angiogenesis and Endothelial Function

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Christian Werner ◽  
Stephan H Schirmer ◽  
Valerie Pavlickova ◽  
Michael Böhm ◽  
Ulrich Laufs
Keyword(s):  
Endothelial Function ◽  
Vascular Function ◽  
Daily Injection ◽  
Peroxisome Proliferator ◽  
Fluorescent Microspheres ◽  
Artery Ligation ◽  
Peroxisome Proliferator Activated Receptor ◽  
Beneficial Effects ◽  
And Function

Objective: Peroxisome proliferator-activated receptor (PPAR)-α and -γ agonists modify lipid and glucose metabolism. The aim of the study was to characterize the effects of the dual PPAR-α/γ agonist aleglitazar on endothelial function, neoangiogenesis and arteriogenesis in mice and on human endothelial progenitor cells (EPC). Methods and Results: Male C57Bl/6 wild-type (WT, normal chow) and apolipoprotein E-deficient (apoE-/-) mice on Western-type diet (WTD) were treated with aleglitazar (10 mg/kg i.p.) or vehicle by daily injection. Hindlimb ischemia was induced by right femoral artery ligation (FAL). ApoE-/- mice on WTD treated with aleglitazar before FAL were characterized by an improvement of endothelial-dependent laser Doppler perfusion (right/left foot ratio 0.40±0.03) 1 week after FAL compared to controls (R/L foot ratio 0.24±0.01; p<0.001). Collateral-dependent perfusion measured under conditions of maximal vasodilatation 1 week after FAL using fluorescent microspheres was impaired in apoE-/- on WTD compared to WT mice (R/L leg ratio in WT 78±13 vs. apoE-/- 56±6; p<0.001) and was normalized by aleglitazar treatment. Neoangiogenesis was measured in-vivo by subcutaneously implanting discs covered with cell-impermeable filters. The vascularized area of the discs was quantified after 14 days by perfusion of the animals with space-filling fluorescent microspheres. Aleglitazar increased neoangiogenesis in WT mice by 178±18% compared to vehicle (p<0.05). Endothelium-dependent relaxation of aortic rings was impaired in apoE-/- mice on WTD for 6 weeks (relaxation to 52±5% of max. contraction) compared to WT animals (relaxation to 18±5% of max. contraction) (p<0.001). Aleglitazar treatment improved endothelial function (relaxation to 39±5% of max. contraction; p<0.05). In parallel, number and function of EPC were improved in mice. Studies in human EPC showed that 1) aleglitazar’s effects were mediated by both PPAR-α and -γ signalling and Akt and 2) migration and colony forming units were up-regulated by aleglitazar in cultivated EPC from CAD patients. Conclusion: The study provides evidence for beneficial effects of the dual PPAR-α/γ agonist aleglitazar on vascular function in addition to or mediated by its metabolic actions.

scholarly journals Conjugated linoleic acids attenuate FSH- and IGF1-stimulated cell proliferation; IGF1, GATA4, and aromatase expression; and estradiol-17β production in buffalo granulosa cells involving PPARγ, PTEN, and PI3K/Akt

Reproduction ◽  
2012 ◽  
Vol 144 (3) ◽  
pp. 373-383 ◽  
Author(s):  
Isha Sharma ◽  
Dheer Singh
Keyword(s):  
Cell Proliferation ◽  
Granulosa Cell ◽  
Granulosa Cells ◽  
Cell Function ◽  
Endocrine System ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Beneficial Effects ◽  
Tensin Homolog ◽  
Estradiol 17Β

Conjugated linoleic acid (CLA) has drawn much interest in last two decades in the area ranging from anticancer activity to obesity. A number of research papers have been published recently with regard to CLA's additional biological functions as reproductive benefits. However, not much is known how this mixture of isomeric compounds mediates its beneficial effects particularly on fertility. In this study, we demonstrated the cross talk between downstream signaling of CLA and important hormone regulators of endocrine system, i.e. FSH and IGF1, on buffalo granulosa cell function (proliferation and steroidogenesis). Experiments were performed in primary serum-free buffalo granulosa cell culture, where cells were incubated with CLA in combination with FSH (25 ng/ml) and IGF1 (50 ng/ml). Results showed that 10 μM CLA inhibits FSH- and IGF1-induced granulosa cell proliferation; aromatase,GATA4, andIGF1mRNA; and estradiol-17β production. Western blot analysis of total cell lysates revealed that CLA intervenes the IGF1 signaling by decreasing p-Akt. In addition, CLA was found to upregulate peroxisome proliferator-activated receptor-gamma (PPARG) and phosphatase and tensin homolog (PTEN) level in granulosa cells. Further study using PPARG- and PTEN-specific inhibitors supports the potential role of CLA in granulosa cell proliferation and steroidogenesis involving PPARG, PTEN, and PI3K/Akt pathway.

scholarly journals Effect of 12 Months of Exercise with Stachys Lavandulifolia Consumption on anxiety, Metabolic Syndrome Profiles and Antioxidant Defense and Lipid Peroxidation in Women with Syndrome Metabolic

2020 ◽  
Author(s):  
Ali osali ◽  
Alireza Rostami
Keyword(s):  
Metabolic Syndrome ◽  
Lipid Peroxidation ◽  
Aerobic Exercise ◽  
Antioxidant Defense ◽  
Training Group ◽  
Serum Levels ◽  
Control Group ◽  
Negative Effects ◽  
Beneficial Effects ◽  
Before And After

Abstract BackgroundThe purpose of this study was to investigate the effect of 12 months of aerobic exercise combining stachys lavandulifolia (S. lavandulifolia) consumption on anxiety, Metabolic Syndrome profiles and antioxidant defense (Glutathione) and lipid peroxidation (Malondialdehyde) in 50-65 years old women with syndrome metabolic.Methods48 women with syndrome Metabolic were randomly divided into four groups: exercise (n=12), exercise+S. lavandulifolia (n=12), S. lavandulifolia (n=12) and control group (n=12). S. lavandulifolia groups consumed 3 g aerial parts of S. lavandulifolia daily. Training groups performed an exercise protocol of aerobic exercise for 12 months (three sessions per week). Blood samples were obtained before and after training period for antioxidant indicators and lipid degradation measurement. Also, Beck anxiety questionnaire used for evaluating levels of anxiety. T-test and one-way analysis of variance were used for the evaluation of within-group and between-group differences, respectively.ResultsA significant increase was observed in serum levels of Malondialdehyde (P =0.004), Catalase indexes (Pvalue= 0.01), and Glutathione (P=0.001) in the training group and S. lavandulifolia groups after 12 months. Body weight, BMI, and SBP and Anexiety was decreased significantly greater in exercise +S. lavandulifolia group compared to control, exercise and S. lavandulifolia groups (P=0.001)ConclusionAnxiolytic effect and Anti-Oxidative Stress Activity was seen, so taking S. lavandulifolia along with exercises may have beneficial effects on reinforcement the antioxidant system and prevention of anxiety and The negative effects of indicators related to cardiovascular disease in women with metabolic syndrome.

scholarly journals Conjugated Linoleic Acid and Brain Metabolism: A Possible Anti-Neuroinflammatory Role Mediated by PPARα Activation

2021 ◽  
Vol 11 ◽  
Author(s):  
Elisabetta Murru ◽  
Gianfranca Carta ◽  
Claudia Manca ◽  
Valeria Sogos ◽  
Marco Pistis ◽  
...  
Keyword(s):  
Linoleic Acid ◽  
Conjugated Linoleic Acid ◽  
Inflammatory Responses ◽  
Feedback Mechanism ◽  
Bioactive Metabolites ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Beneficial Effects ◽  
Cellular Effects ◽  
Positive Feedback Mechanism

Fatty acids play a crucial role in the brain as specific receptor ligands and as precursors of bioactive metabolites. Conjugated linoleic acid (CLA), a group of positional and geometric isomers of linoleic acid (LA, 18:2 n-6) present in meat and dairy products of ruminants and synthesized endogenously in non-ruminants and humans, has been shown to possess different nutritional properties associated with health benefits. Its ability to bind to peroxisome proliferator-activated receptor (PPAR) α, a nuclear receptor key regulator of fatty acid metabolism and inflammatory responses, partly mediates these beneficial effects. CLA is incorporated and metabolized into brain tissue where induces the biosynthesis of endogenous PPARα ligands palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), likely through a positive feedback mechanism where PPARα activation sustains its own cellular effects through ligand biosynthesis. In addition to PPARα, PEA and OEA may as well bind to other receptors such as TRPV1, further extending CLA own anti-neuroinflammatory actions. Future studies are needed to investigate whether dietary CLA may exert anti-inflammatory activity, particularly in the setting of neurodegenerative diseases and neuropsychiatric disorders with a neuroinflammatory basis.

Recent Updates on Peroxisome Proliferator-Activated Receptor δ Agonists for the Treatment of Metabolic Syndrome

2016 ◽  
Vol 12 (1) ◽  
pp. 3-21 ◽  
Author(s):  
Ajmer S. Grewal ◽  
Meenu Beniwal ◽  
Deepti Pandita ◽  
Bhupinder S. Sekhon ◽  
Viney Lather
Keyword(s):  
Metabolic Syndrome ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor
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