Resveratrol and quercetin are two functional ingredients to which a fat-reducing effect has been attributed in various experiments conducted in vivo and in vitro. Yet their rapid metabolism means that only a tiny fraction of these compounds reach organs and tissue. Now a new piece of research suggests that their metabolism should not be regarded as a limitation in the use of resveratrol in pre-adipocytes nor in the use of quercetin in mature adipocytes.
Resveratrol and quercetin metabolites contribute towards the anti-obesity effect of both molecules
A PhD thesis of the UPV/EHU-University of the Basque Country shows that despite their metabolism they maintain their biological activity and also help to reduce fat
First publication date: 11/11/2019
Obesity is defined as excess accumulation of body fat, which can result in the development of a whole range of comorbidities. According to the World Health Organisation (WHO), in 2016 39% of adults were overweight and 13% obese. What is more, 41 million children under five are overweight or obese, and 340 million in the case of children and teenagers between the ages of 5 and 19.
Phenolic compounds are antioxidants that occur naturally in plants which produce them in response to stress as a defence mechanism. Thanks to various studies, a diet rich in phenolic compounds has been seen to help to maintain an optimum state of health and reduce the occurrence of various diseases, such as cardiovascular diseases, cancer, diabetes, etc. When phenolic compounds have more than one phenolic ring in their structure, these compounds are then known as polyphenols, a more widely-known term. Resveratrol and quercetin are currently two of the most studied polyphenols.
The beneficial effects of resveratrol were first described in 1982, when, thanks to an observational study, an inverse relationship was established between moderate wine consumption and the prevalence of cardiovascular disease. This observation later became known as the “French Paradox”. This polyphenol is found mostly in grapes and the beverages made from them (grape juice and wine), berries and peanuts, among other things, and various biological functions have been attributed to it, such as antioxidant, anti-inflammatory, immunomodulating, anti-diabetic and anti-carcinogenic functions. It has also been found to have anti-obesity functions owing to the reduction in body fat brought about by various mechanisms, such as food intake modulation, modification of nutrient absorption, regulation of the cell cycle of adipocytes, reduction in adipose tissue inflammation, regulation of mitochondrial function, induction of thermogenesis, and modulation of intestinal microbiota.
Activity following metabolism
The PhD thesis read by Itziar Eseberri-Barace takes this research a step further and has demonstrated that certain metabolites of resveratrol and quercetin molecules, in other words the products that remain following their digestion, remain biologically active and partly contribute towards the anti-obesity effect of the compounds. “The results obtained show that all the metabolites analysed from the resveratrol contribute to the same degree as the polyphenol towards inhibiting adipogenesis. Although they are active in mature adipocytes, resveratrol is much more effective. In the case of quercetin, this effect can only be attributed to the sulphated metabolite (quercetin-3-0-sulphate) in mature adipocytes, since none of the quercetin metabolites turned out to be as effective as or more effective than the polyphenol on its own in inhibiting adipogenesis,” explained the researcher. “It can therefore be concluded that the metabolism of these two compounds can signify a limitation only in the case of mature adipocytes treated with resveratrol and pre-adipocytes in differentiation treated with quercetin.”
Quercetin is found in larger amounts in apples, onions, cherries, berries, broccoli and tea. Just as in the case of resveratrol, many biological functions have been attributed to it, such as anti-inflammatory, antidiabetic, antihyperternsive, antihypercholesterolemic, antiaterosclerotic and antiobesity functions.
It is necessary to bear in mind that, apart from their low bioavailability, phenolic compounds occur in small quantities in foodstuffs, because, after they have been digested, they undergo extensive metabolization, with the result that the amount that reaches organs and tissue is relatively low. “The amounts of resveratrol and quercetin used in most of the in vitro studies conducted to date for the purpose of studying their effects as anti-obesity molecules are a long way from those that actually reach the tissue, so the use of doses closer to reality has been one of the novel aspects of this work,” specified Itziar Eseberri. “What is more, very few studies have been conducted to check whether the metabolites derived from the metabolism of the two polyphenols have any biological activity on a par with the parent compound.”
So, the thesis aimed to analyse whether the main metabolites of the two compounds in 3T3-L1 adipocytes could be responsible for and contribute towards the fat reduction effect attributed to resveratrol and quercetin, and also to check and compare the action mechanisms responsible for the antiobesity effect of each of the molecules in adipocytes in culture. After conducting various experiments, which gave rise to five scientific papers published in high-impact journals, the work has shown that certain metabolites of both molecules are biologically active and contribute partly towards the antiobesity effect. “There has been partial confirmation of the hypothesis that determines whether the beneficial triglyceride-lowering effects of resveratrol and quercetin can be attributed to them alone or to their principal metabolites as well. Metabolism should not be regarded as a limitation neither in the case of resveratrol in pre-adipocytes in differentiation nor in quercetin in mature adipocytes,” concluded the new doctor.
The PhD thesis by Itziar Eseberri-Barace (Pamplona/Iruñea, 1987), entitled ‘Erresberatrola eta kertzetinaren metabolitoen efektuak 3T3-L1 adipozitoen adipogenesian eta triglizeridoen metabolismoan, hala nola jatorrizko konposatuen efektuekin konparatzea’ (‘Effects of resveratrol and quercetin metabolites in adipogenesis and triglyceride metabolism of 3T3-L1 adipocytes and comparison to those of the parent compounds’), and supervised by Dr Arrate Lasa-Elgezua and Dr Jonatan Miranda-Gómez, was written up and read in Basque and English. The work was conducted within the UPV/EHU’s ‘Nutrition and Obesity’ research group, which belongs to the Networking Biomedical Research Centre – Physiopathology of Obesity and Nutrition (CiberObn), and the Laboratoire de recherche sur les obésités del Institut des Maladies Métaboliques et Cardiovasculaires in Toulouse (France), where the doctoral student spent three months. To produce her PhD thesis she was awarded one of the grants earmarked for the training of UPV/EHU research personnel.
- Resveratrol metabolites modify adipokine expression and secretion in 3T3-L1 pre-adipocytes and mature adipocytes PLoS One, 8(5), e63918 (2013) DOI: 10.1371/journal.pone.0063918
- Potential miRNA involvement in the anti-adipogenic effect of resveratrol and its metabolites PLoS One, 12(9), e0184875 (2017) DOI: 10.1371/journal.pone.0184875
- Doses of Quercetin in the Range of Serum Concentrations Exert Delipidating Effects in 3T3-L1 Preadipocytes by Acting on Different Stages of Adipogenesis, but Not in Mature Adipocytes Oxid Med Cell Longev, 2015, 480943 (2015) DOI: 10.1155/2015/480943
- Effects of Quercetin Metabolites on Triglyceride Metabolism of 3T3-L1 Preadipocytes and Mature Adipocytes Int J Mol Sci, 20(2) (2019) DOI: 10.3390/ijms20020264
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