Mitochondrial metabolism as a target for human metabolites of dietary anthocyanins

KROON_Q23DTP

Anthocyanins are the polyphenolic compounds responsible for the red-purple-blue colour of fruits and vegetables such as strawberries, blackcurrants, aubergines and blueberries.

Evidence from epidemiological and dietary intervention studies in humans shows that consuming these compounds has beneficial effects on metabolic biomarkers and protects against metabolic diseases such as diabetes and metabolic syndrome.

Anthocyanins are very poorly absorbed and recently we and others have identified the main human metabolites of anthocyanins in the circulation; these are small ring fission metabolites formed in the gut and can reach micromolar concentrations in the blood, orders of magnitude higher than the parent anthocyanins.

In this project, the student will measure the effects of these human metabolites on mitochondrial metabolism, and investigate the mechanisms of action.
The student will be trained to use state-of-the-art Seahorse analysers to investigate the effects of these little studied compounds on mitochondrial energetics in real time in live cells and in the use of pulse-chase methods.

They will also be trained in metabolite profiling techniques using LC-MS platforms and in the use of RNASeq and bioinformatics pipelines to study changes in transcript profiles.

The student will be encouraged to develop hypotheses and to design appropriate experiments to test these.

The student will join a vibrant group in the Food, Microbiomes and Health Programme in the Quadram Institute in a brand new, purpose built building with state of the art facilities. The Quadram Institute is based on the Norwich Research Park and is home to the largest community of Agri-Food researchers in Europe.

The student will join a large cohort of graduate researchers in QIB and on the Norwich Research Park with exceptional training opportunities in laboratory methods, bioinformatics analyses and personal and professional development.

Informal enquiries can be sent to paul.kroon@quadram.ac.uk.

References

1. Aboufarrag HT, Needs PW, Rimbach G, Kroon PA (2019). The effects of anthocyanins and their microbial metabolites on the expression and enzyme activities of paraoxonase 1, an important marker of HDL function. Nutrients 2019, 11 (12), 2872. Doi: 10.339/nu11122872.

2. Ozyel B, Le Gall G, Needs PW, Kroon PA (2020). Anti-inflammatory effects of quercetin on high-glucose and proinflammatory cytokine challenged vascular endothelial cell metabolism. Mol Nutr Food Res. Article Number: 2000777. DOI: 10.1002/mnfr.202000777.

3. Prpa EJ, Corpe CP, Atkinson B, Blackstone B, Leftley ES, Parekh P, Philo M, Kroon PA, Hall WL (2020). Apple polyphenol-rich drinks dose-dependently decrease early-phase postprandial glucose concentrations following a high-carbohydrate meal: A randomised controlled trial in healthy adults and in vitro studies. J Nutr Biochem 85, article no. 108466. https://doi.org/10.1016/ j.jnutbio.2020.108466.

4. Day-Walsh PE, Keeble B, Pirabagar G, Fountain SJ, Kroon PA (2022). Transcriptional and post-translational regulation of junctional adhesion molecule-B (JAM-B) in leukocytes under inflammatory stimuli. Int J Mol Sci 23, 8646. https://doi.org/10.3390/ijms23158646.

5. Day-Walsh P, Shehata E, Saha S, Savva GM, Nemeckova B, Speranza J, Kellingray L, Narbad A, Kroon PA (2021). The use of an in-vitro batch fermentation (human colon) model for investigating mechanisms of TMA production from choline, L-carnitine and related precursors by the human gut microbiota. Eur J Nutr. doi.org/10.1007/s00394-021-02572-6.