Effect-directed analysis and chemical identification of agonists of peroxisome proliferator-activated receptors in white button mushroom

Obesity has a serious effect on human health. It relates to metabolic syndrome, including the associated disorders such as type 2 diabetes, heart disease, stroke and hyperemia. The peroxisome proliferator-activated receptors (PPARs) are important receptors to control fat metabolism in the human body...

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Bibliographic Details
Published in:Food & function 2021-01, Vol.12 (1), p.133-143
Main Authors: Pham Ngoc, Long, Helmus, Rick, Ehlers, Andreas W, Swart, Kees, Besselink, Harry, de Rijke, Eva, Dang Thi Cam, Ha, Brouwer, Abraham, van der Burg, Bart
Format: Article
Language:English
Subjects:
Agonists
Basidiocarps
Cardiovascular diseases
Coronary artery disease
Diabetes mellitus (non-insulin dependent)
Diet
Drug delivery
Energy intake
Fat metabolism
Fatty acids
Fractionation
Heart diseases
Hyperemia
Ligands
Linoleic acid
Metabolic disorders
Metabolic syndrome
Mushrooms
NMR
Nuclear magnetic resonance
Obesity
Peroxisome proliferator-activated receptors
Receptors
Reporter gene
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Summary:Obesity has a serious effect on human health. It relates to metabolic syndrome, including the associated disorders such as type 2 diabetes, heart disease, stroke and hyperemia. The peroxisome proliferator-activated receptors (PPARs) are important receptors to control fat metabolism in the human body. Because of the safety concerns of synthetic drugs targeting PPARs, ligands from natural sources have drawn interest. Earlier, we have found high PPAR activities in extracts from Agaricus bisporus (white button mushroom, WBM). WBM contains a wide range of candidate compounds which could be agonists of PPARs. To identify which compounds are responsible for PPAR activation by WBM extracts, we used fractionation coupled to effect-directed analysis with reporter gene assays specific for all three PPARs for purification and LC/MS-TOF and NMR for compound identification in purified active fractions. Surprisingly, we identified the relatively common dietary fatty acid, linoleic acid, as the main ligand of PPARs in WBM. Possibly, the relatively low levels of linoleic acid in WBM are sufficient and instrumental in inducing its anti-obesogenic effects, avoiding high energy intake and negative health effects associated with high levels of linoleic acid consumption. However, it could not be excluded that a minor relatively potent compound contributes towards PPAR activation, while the anti-obesity effects of WBM may be further enhanced by receptor expression modulating compounds or compounds with completely PPAR unrelated modes of action. Linoleic acid is the main PPAR ligand in white button mushrooms and may be involved in their anti-obesogenic effect.
ISSN:2042-6496
2042-650X
DOI:10.1039/d0fo02071k