scholarly journals Intestinal microbe-dependent ω3 lipid metabolite αKetoA prevents inflammatory diseases in mice and cynomolgus macaques

2022 ◽  
Author(s):  
Takahiro Nagatake ◽  
Shigenobu Kishino ◽  
Emiko Urano ◽  
Haruka Murakami ◽  
Nahoko Kitamura ◽  
...  
Keyword(s):  
Linolenic Acid ◽  
Octadecadienoic Acid ◽  
Inflammatory Diseases ◽  
Linseed Oil ◽  
Dietary Lipids ◽  
Contact Hypersensitivity ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Cynomolgus Macaques

AbstractDietary ω3 fatty acids have important health benefits and exert their potent bioactivity through conversion to lipid mediators. Here, we demonstrate that microbiota play an essential role in the body’s use of dietary lipids for the control of inflammatory diseases. We found that amounts of 10-hydroxy-cis-12-cis-15-octadecadienoic acid (αHYA) and 10-oxo-cis-12-cis-15-octadecadienoic acid (αKetoA) increased in the feces and serum of specific-pathogen-free, but not germ-free, mice when they were maintained on a linseed oil diet, which is high in α-linolenic acid. Intake of αKetoA, but not αHYA, exerted anti-inflammatory properties through a peroxisome proliferator-activated receptor (PPAR)γ-dependent pathway and ameliorated hapten-induced contact hypersensitivity by inhibiting the development of inducible skin-associated lymphoid tissue through suppression of chemokine secretion from macrophages and inhibition of NF-κB activation in mice and cynomolgus macaques. Administering αKetoA also improved diabetic glucose intolerance by inhibiting adipose tissue inflammation and fibrosis through decreased macrophage infiltration in adipose tissues and altering macrophage M1/M2 polarization in mice fed a high-fat diet. These results collectively indicate that αKetoA is a novel postbiotic derived from α-linolenic acid, which controls macrophage-associated inflammatory diseases and may have potential for developing therapeutic drugs as well as probiotic food products.

scholarly journals Recent Insights on the Role of PPAR-β/δ in Neuroinflammation and Neurodegeneration, and Its Potential Target for Therapy

2020 ◽  
Author(s):  
Anna K. Strosznajder ◽  
Sylwia Wójtowicz ◽  
Mieszko J. Jeżyna ◽  
Grace Y. Sun ◽  
Joanna B. Strosznajder
Keyword(s):  
Fatty Acids ◽  
Traumatic Injury ◽  
Brain Regions ◽  
Dietary Lipids ◽  
Peroxisome Proliferator ◽  
Special Role ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
The Impact ◽  
Long Chain

AbstractPeroxisome proliferator-activated receptor (PPAR) β/δ belongs to the family of hormone and lipid-activated nuclear receptors, which are involved in metabolism of long-chain fatty acids, cholesterol, and sphingolipids. Similar to PPAR-α and PPAR-γ, PPAR-β/δ also acts as a transcription factor activated by dietary lipids and endogenous ligands, such as long-chain saturated and polyunsaturated fatty acids, and selected lipid metabolic products, such as eicosanoids, leukotrienes, lipoxins, and hydroxyeicosatetraenoic acids. Together with other PPARs, PPAR-β/δ displays transcriptional activity through interaction with retinoid X receptor (RXR). In general, PPARs have been shown to regulate cell differentiation, proliferation, and development and significantly modulate glucose, lipid metabolism, mitochondrial function, and biogenesis. PPAR-β/δ appears to play a special role in inflammatory processes and due to its proangiogenic and anti-/pro-carcinogenic properties, this receptor has been considered as a therapeutic target for treating metabolic syndrome, dyslipidemia, carcinogenesis, and diabetes. Until now, most studies were carried out in the peripheral organs, and despite of its presence in brain cells and in different brain regions, its role in neurodegeneration and neuroinflammation remains poorly understood. This review is intended to describe recent insights on the impact of PPAR-β/δ and its novel agonists on neuroinflammation and neurodegenerative disorders, including Alzheimer’s and Parkinson’s, Huntington’s diseases, multiple sclerosis, stroke, and traumatic injury. An important goal is to obtain new insights to better understand the dietary and pharmacological regulations of PPAR-β/δ and to find promising therapeutic strategies that could mitigate these neurological disorders.

scholarly journals Andrographis paniculata and Its Main Bioactive Ingredient Andrographolide Decrease Alcohol Drinking and Seeking in Rats Through Activation of Nuclear PPARγ Pathway

2021 ◽  
Author(s):  
Serena Stopponi ◽  
Yannick Fotio ◽  
Carlo Cifani ◽  
Hongwu Li ◽  
Carolina L Haass-Koffler ◽  
...  
Keyword(s):  
Oral Administration ◽  
Alcohol Drinking ◽  
Andrographis Paniculata ◽  
Peroxisome Proliferator ◽  
Herbaceous Plant ◽  
Dependent Manner ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Treatment Administration ◽  
Dried Extract

Abstract Background and aims Andrographis paniculata is an annual herbaceous plant which belongs to the Acanthaceae family. Extracts from this plant have shown hepatoprotective, anti-inflammatory and antidiabetic properties, at least in part, through activation of the nuclear receptor Peroxisome Proliferator-Activated Receptor-gamma (PPAR γ). Recent evidence has demonstrated that activation of PPARγ reduces alcohol drinking and seeking in Marchigian Sardinian (msP) alcohol-preferring rats. Methods The present study evaluated whether A. paniculata reduces alcohol drinking and relapse in msP rats by activating PPARγ. Results Oral administration of an A. paniculata dried extract (0, 15, 150 mg/kg) lowered voluntary alcohol consumption in a dose-dependent manner and achieved ~65% reduction at the dose of 450 mg/kg. Water and food consumption were not affected by the treatment. Administration of Andrographolide (5 and 10 mg/kg), the main active component of A. paniculata, also reduced alcohol drinking. This effect was suppressed by the selective PPARγ antagonist GW9662. Subsequently, we showed that oral administration of A. paniculata (0, 150, 450 mg/kg) prevented yohimbine- but not cues-induced reinstatement of alcohol seeking. Conclusions Results point to A. paniculata-mediated PPARγactivation as a possible therapeutic strategy to treat alcohol use disorder.

scholarly journals Diet and PPARG2 Pro12Ala Polymorphism Interactions in Relation to Cancer Risk: A Systematic Review

Nutrients ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 261
Author(s):  
Lieu Tran ◽  
Gerd Bobe ◽  
Gayatri Arani ◽  
Yang Zhang ◽  
Zhenzhen Zhang ◽  
...  
Keyword(s):  
Cancer Risk ◽  
Dietary Factors ◽  
Dietary Fats ◽  
Current Evidence ◽  
Peroxisome Proliferator ◽  
Allele Polymorphism ◽  
Peroxisome Proliferator Activated Receptor ◽  
Complex Relation ◽  
Ppar Γ ◽  
Pubmed Database

Peroxisome proliferator-activated receptor-γ2 gene Pro12Ala allele polymorphism (PPARG2 Pro12Ala; rs1801282) has been linked to both cancer risk and dietary factors. We conducted the first systematic literature review of studies published before December 2020 using the PubMed database to summarize the current evidence on whether dietary factors for cancer may differ by individuals carrying C (common) and/or G (minor) alleles of the PPARG2 Pro12Ala allele polymorphism. The inclusion criteria were observational studies that investigated the association between food or nutrient consumption and risk of incident cancer stratified by PPARG2 Pro12Ala allele polymorphism. From 3815 identified abstracts, nine articles (18,268 participants and 4780 cancer cases) covering three cancer sites (i.e., colon/rectum, prostate, and breast) were included. CG/GG allele carriers were more impacted by dietary factors than CC allele carriers. High levels of protective factors (e.g., carotenoids and prudent dietary patterns) were associated with a lower cancer risk, and high levels of risk factors (e.g., alcohol and refined grains) were associated with a higher cancer risk. In contrast, both CG/GG and CC allele carriers were similarly impacted by dietary fats, well-known PPAR-γ agonists. These findings highlight the complex relation between PPARG2 Pro12Ala allele polymorphism, dietary factors, and cancer risk, which warrant further investigation.

scholarly journals Abdominal Fat SIRT6 Expression and Its Relationship with Inflammatory and Metabolic Pathways in Pre-Diabetic Overweight Patients

2019 ◽  
Vol 20 (5) ◽  
pp. 1153 ◽  
Author(s):  
Nunzia D’Onofrio ◽  
Gorizio Pieretti ◽  
Feliciano Ciccarelli ◽  
Antonio Gambardella ◽  
Nicola Passariello ◽  
...  
Keyword(s):  
Regulatory Element ◽  
Abdominal Fat ◽  
Control Group ◽  
Diabetic Patients ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Metformin Therapy ◽  
Ppar Γ ◽  
Visceral Abdominal Fat ◽  
Factor Α

: The role of sirtuin 6 (SIRT6) in adipose abdominal tissue of pre-diabetic (pre-DM) patients is poorly known. Here, we evaluated SIRT6 expression in visceral abdominal fat of obese pre-diabetic patients and the potential effects of metformin therapy. Results indicated that obese pre-DM subjects showed low SIRT6 protein expression and high expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), peroxisome proliferator-activated receptor gamma (PPAR-γ), and sterol regulatory element-binding transcription factor 1 (SREBP-1). Obese pre-DM patients showed high values of glucose, insulin resistance (HOMA-IR), C reactive protein (CRP), nitrotyrosine, tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6), and low values of insulin (p < 0.05). Of note, abdominal fat tissue of obese pre-DM patients treated with metformin therapy presented higher SIRT6 expression and lower NF-κB, PPAR-γ, and SREBP-1 expression levels compared to pre-DM control group. Collectively, results show that SIRT6 is involved in the inflammatory pathway of subcutaneous abdominal fat of obese pre-DM patients and its expression responds to metformin therapy.

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