Synthetic and natural Peroxisome Proliferator-Activated Receptor (PPAR) agonists as candidates for the therapy of the metabolic syndrome

Tan, Chee Leong; Zhuang, Yan; Wahli, Walter

doi:10.1080/14728222.2017.1280467

Cited by 57 publications

(56 citation statements)

References 121 publications

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“…Although activation of PPARs by several synthetic drugs has been Each PPAR isotype has its own group of natural and synthetic ligands, although some ligands interact with .1 isotype. The natural ligands are either derived endogenously or from our diet (78,95,96,267,268). PPAR ligands have been reviewed extensively (78,95,96,267,268); therefore, only general information is provided here.…”

Section: Pparsmentioning

confidence: 99%

The PPAR–microbiota–metabolic organ trilogy to fine‐tune physiology

Visvalingam

Wahli

2019

FASEB j.

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The human gut is colonized by commensal microorganisms, predominately bacteria that have coevolved in symbiosis with their host. The gut microbiota has been extensively studied in recent years, and many important findings on how it can regulate host metabolism have been unraveled. In healthy individuals, feeding timing and type of food can influence not only the composition but also the circadian oscillation of the gut microbiota. Host feeding habits thus influence the type of microbe‐derived metabolites produced and their concentrations throughout the day. These microbe‐derived metabolites influence many aspects of host physiology, including energy metabolism and circadian rhythm. Peroxisome proliferator‐activated receptors (PPARs) are a group of ligand‐activated transcription factors that regulate various metabolic processes such as fatty acid metabolism. Similar to the gut microbiota, PPAR expression in various organs oscillates diurnally, and studies have shown that the gut microbiota can influence PPAR activities in various metabolic organs. For example, short‐chain fatty acids, the most abundant type of metabolites produced by anaerobic fermentation of dietary fibers by the gut microbiota, are PPAR agonists. In this review, we highlight how the gut microbiota can regulate PPARs in key metabolic organs, namely, in the intestines, liver, and muscle. Knowing that the gut microbiota impacts metabolism and is altered in individuals with metabolic diseases might allow treatment of these patients using noninvasive procedures such as gut microbiota manipulation.—Oh, H. Y. P., Visvalingam, V., Wahli, W. The PPAR–microbiota–metabolic organ trilogy to fine‐tune physiology. FASEB J. 33, 9706–9730 (2019). http://www.fasebj.org

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Section: Pparsmentioning

confidence: 99%

The PPAR–microbiota–metabolic organ trilogy to fine‐tune physiology

Visvalingam

Wahli

2019

FASEB j.

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“…5-aminoimidazole-4-carboxamide ribonucleotide (AICAR)], increased running endurance [80]. However, there are currently no approved PPAR-δ agonists [81], and neither is there evidence for performance enhancement in humans. Similarly, specific AMPK activators are not approved (such as AICAR), although there are approved drugs that have an AMPK activating effect, e.g.…”

Section: Resultsmentioning

confidence: 99%

Review of WADA Prohibited Substances: Limited Evidence for Performance-Enhancing Effects

Heuberger

Cohen

2018

Sports Med

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The World Anti-Doping Agency is responsible for maintaining a Prohibited List that describes the use of substances and methods that are prohibited for athletes. The list currently contains 23 substance classes, and an important reason for the existence of this list is to prevent unfair competition due to pharmacologically enhanced performance. The aim of this review was to give an overview of the available evidence for performance enhancement of these substance classes. We searched the scientific literature through PubMed for studies and reviews evaluating the effects of substance classes on performance. Findings from double-blind, randomized controlled trials were considered as evidence for (the absence of) effects if they were performed in trained subjects measuring relevant performance outcomes. Only 5 of 23 substance classes show evidence of having the ability to enhance actual sports performance, i.e. anabolic agents, β2-agonists, stimulants, glucocorticoids and β-blockers. One additional class, growth hormone, has similar evidence but only in untrained subjects. The observed effects all relate to strength or sprint performance (and accuracy for β-blockers); there are no studies showing positive effects on reliable markers of endurance performance. For 11 classes, no well-designed studies are available, and, for the remaining six classes, there is evidence of an absence of a positive effect. In conclusion, for the majority of substance classes, no convincing evidence for performance enhancement is available, while, for the remaining classes, the evidence is based on a total of only 266 subjects from 11 studies.

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“…Moreover, the activity profile of the C. karianus oxo-fatty acids, as well as derivatives thereof, should be compared with the profile of other promising dual PPARα/γ agonists, like Saroglitazar [35]. Saroglitazar is marketed in Asia and displays significant improvement in both glycemic as well as dyslipidemic parameters with no evidence of conventional side effects (as reviewed in [25]). From a structural perspective, a recent study by Yore et al [36] who made use of quantitative MS to identify metabolic changes in transgenic Glut4 mice is highly interesting.…”

Section: Resultsmentioning

confidence: 99%

“…However, adverse side effects have been reported, especially for the TZDs [21,22]. One way to avoid these problems has been to find or design partial [23,24] or dual [25,26] agonists which in general seems to come with fewer side effects. Thus, the aim of the present work was to identify compounds from marine organisms that regulate PPAR activity, and that may serve as molecular scaffolds for the development of novel, safer PPAR-targeting drugs.…”

Section: Introductionmentioning

confidence: 99%

Two Isomeric C16 Oxo-Fatty Acids from the Diatom Chaetoceros karianus Show Dual Agonist Activity towards Human Peroxisome Proliferator-Activated Receptors (PPARs) α/γ

et al. 2017

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The peroxisome proliferator-activated receptors (PPARs) function as ligand-activated transcription factors that convert signals in the form of lipids to physiological responses through the activation of metabolic target genes. Due to their key roles in lipid and carbohydrate metabolism, the PPARs are important drug targets. However, for several of the PPAR drugs currently in use, adverse side effects have been reported. In an effort to identify compounds from marine organisms that may serve as molecular scaffolds for the development of novel and safer PPAR-targeting drugs, we performed a bioassay-guided screening of organic extracts made from organisms supplied by the Norwegian Biobank of Arctic Marine Organisms (Marbank). Among several interesting hits, we identified two poorly described isomeric oxo-fatty acids from the microalgae Chaetoceros karianus for which we provide the first evidence that they might display dual specificity towards human PPARα and PPARγ. Principal component analysis showed that C. karianus stood out from other Chaetoceros species, both with respect to the metabolic profile and the PPAR activity. The isolation of these compounds holds the potential of uncovering a PPAR pharmacophore with tunable activity and specificity.

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Synthetic and natural Peroxisome Proliferator-Activated Receptor (PPAR) agonists as candidates for the therapy of the metabolic syndrome

Cited by 57 publications

References 121 publications

The PPAR–microbiota–metabolic organ trilogy to fine‐tune physiology

The PPAR–microbiota–metabolic organ trilogy to fine‐tune physiology

Review of WADA Prohibited Substances: Limited Evidence for Performance-Enhancing Effects

Two Isomeric C16 Oxo-Fatty Acids from the Diatom Chaetoceros karianus Show Dual Agonist Activity towards Human Peroxisome Proliferator-Activated Receptors (PPARs) α/γ

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