A novel direction on exploring metabolic beneficial effect of dietary interventions- involving gut microbiome, the gut hormone GLP-1, and the liver hormone FGF21
Description: Dietary polyphenols (DPs) possess metabolic beneficial effects in animals and human subjects. Among them, resveratrol (REV) intervention (REV-I) reduces blood glucose and lipid levels and improves insulin sensitivity, making it a candidate for the "treatment" and prevention of diabetes, fatty liver diseases and their cardiovascular complications. However, the mechanism remains unclear. We reported that the bacteria residing in the gut (i.e., gut microbiome) is the main target of REV-I. We have long term track record in exploring functions of diabetes drugs known as GLP-1 receptor agonists (GLP-1RA, i.e., Liraglutide). Liraglutide was shown to target hepatic hormone FGF21 and FGF21 is also the common target of GLP-1RAs and DPs. FGF21 analogues attenuate blood lipid level and improve insulin sensitivity in several clinical trials. Based on those findings, I plan to connect the dots and hypothesize that mechanisms underlying beneficial effects of DPs are mediated via changes in the gut microbiome, this in turn changes gut environment and hormones like GLP-1 and FGF21 by either altering their production or function. To test this, I will utilize cellular and mouse models to address how REV-I works with gut microbiome to regulate the function of GLP-1-producing cells (Aim I). Furthermore, I will also determine whether liver hormone FGF21 is required for REV-I to exert its beneficial effects (Aim II). For the past 2-3 decades, beneficial effects of DPs have been extensively studied, yet very little is known about how they work. Our findings on the interaction between DPs and gut microbiome lay the groundwork and inspire me to further study this. Such study will make fundamental changes in the understanding of DPs, especially by bringing "seemly unrelated" players such as GLP-1 and FGF21. Examining such interaction between DPs, gut microbiome and metabolic hormones will warrant novel therapeutic approaches for future metabolic disease treatment and prevention.
Amount: CA$120,000
Funding type: fellowship
Funder scheme: Doctoral Research Award: Canada Graduate Scholarships
Start date: 2024-09-01
End date: 2027-08-31
Investigator: Jia Nuo Feng
Institution: University of Toronto
Subfield: Geriatrics and Gerontology
Field: Medicine
Domain: Health Sciences
Funded outputs count: 0
Funder award ID: 193395_1
OpenAlex ID: G6853433128