Abstract
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.
Highlights
Obesity has a significant impact on human health, leading to an increased incidence of metabolic syndrome, which is characterized by central obesity, high blood pressure, high blood sugar, high level of triglycerides, and low serum highdensity lipoprotein (HDL)
A complex range of compounds is present in White button mushroom (WBM), which could contribute to its observed anti-obesity effects.[13,16]
A stepwise fractionation was used, directed by activities observed in the bioassays to identify ligands for peroxisome proliferator-activated receptors (PPARs), which are considered important in regulating fat metabolism, and important target receptors to select ligands to combat metabolic syndrome.[5]
Summary
Obesity has a significant impact on human health, leading to an increased incidence of metabolic syndrome, which is characterized by central obesity, high blood pressure, high blood sugar, high level of triglycerides, and low serum highdensity lipoprotein (HDL). It should be noted that there is a possibility that bioactive compounds activating the PPARs would give the same side effects as the current pharmaceuticals, if these side effects were inherent to PPAR activation This could be the case, and there are concerns and controversies regarding the effects of PPARδ activation on cancer progression.[8] This, may be caused by the complex nature of cancer progression and the many possible points of interaction, together with the differences in the animal and cellular models used.[8] To avoid misinterpretation of these data, the best possible test should be carried out in humans. Since this is not feasible, an alternative is the identification of active molecules in a food item with a long history of safe use, as has been done in the current study
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