Martí-Franquès COFUND Fellowship Programme


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Reference:

2020MFP-COFUND-2

Area:

Health Sciences

Supervisor name and surname:

Anna Ardévol Grau

Supervisor email:

anna.ardevol@urv.cat

Supervisor short biography

Co-supervisor name and surname:

Montserrat Pinent Armengol

Co-supervisor email:

montserrat.pinent@urv.cat

Co-supervisor institution:

URV

Co-supervisor short biography

PhD programme:

Nutrition and Metabolism

Title of the research project:

Ecnomotopic bitter taste receptors as targets for better health in the obesity or the ageing

Description of the research project:

1) The idea of the project and where it sits within the state-of-the-art

Life expectancy is increasing among the world population, being obesity and its comorbidities a major public health problem that are reaching pandemic proportions. This fact makes obesity and ageing two main challenges to tackle in order to improve our quality of life. Both dietary habits and food composition contribute to the onset of obesity and related metabolic disorders. Also, ageing is implicated although there is not a consensus on the main factors implicated[1].
One of the recent focus in the fight against obesity is the study of intestinal dysfunction, which is characterized by altered gut microbiota, impaired enteroendocrine system, inflammation and gut barrier disruption, according to animal and human studies[2]. Also, the ageing processes alter some intestinal functions. Changes on incretin profile[3], mucosal permeability and low-grade inflammation[4], have been suggested to contribute to ageing derangements.
The gastrointestinal tract (GI) has, among its various functions, the responsibility to inform and protect the body from a wide variety of chemical structures. One of the structures that can participate on it are taste receptors (TAS) which have different distribution along the GI tract. TAS have been involved in some biological functions as they have been found at the enteroendocrine cells where they control gut hormone release[5]. But, a more in-depth knowledge about the location of all the different TAS along the GI tract (in which segment and cell type) is required to better understand their role in the development of metabolic diseases and its potential use as therapeutic targets.
These TAS were initially described as G protein-coupled receptors in oral tissues. Bitter, which signals the presence of potentially toxic compounds, is sensed by 25 subtypes of the taste 2 receptor family (TAS2R) in humans[6]. A very novel and interesting field of investigation is that TAS have also been found in non-gustatory tissues (from now on, ecnomotopic taste receptors[7]), however their role in the extra-oral locations is still far from being clear.
A still more unexplored field of study is whether ageing involves derangements in ecnomotopic TAS functions. Taste perception at physiological levels has been shown to decrease proportionally with ageing[8].
In conclusion, previous animal studies highlight the potential of TAS as modulators of metabolic homeostasis, but there is a demand on studies in humans to understand the role of these ecnomotopic TA2S and their potential use as drug targets.

1. Metabolism 2014, 63, 922–7.
2. FASEB J. 2015, 29, 3111–3123.
3. Mech. Ageing Dev. 2004, 125, 871–5.
4. Physiol. Rep. 2014, 2, e00281.
5. Nat. Rev. Drug Discov. 2019, 18, 116–138.
6. Science 2016, 351, 1329–1333.
7. Front. Cell. Infect. Microbiol. 2018, 8, 1–7.
8. Am. J. Clin. Nutr. 2019, 109, 1709–1723.
2.The objectives of the project, as well as the progress beyond the state-of-the-art.

Provided all this data, our hypothesis is that through an optimal stimulation of complementary specific taste receptors (TA2SR) at the gastrointestinal tract, it could be possible to produce the right combinations of enterohormones that help to adjust several of the metabolic disturbances linked to obesity and/or ageing.
To prove this hypothesis, our main aim is to understand the relationship of the different ecnomotopic TAS2Rs with the metabolic status and their affectation by the ageing process in healthy people and the response to bariatric surgery in obese patients.
To achieve this ambitious goal, we will work in the description of the relative presence of the differents TAS2R (25 in humans) in different human intestinal locations and their relationship with difficult situations induced by ageing and obesity. On detail, it would be addressed according to the next objectives:
1. To describe the intestinal presence of the human ecnomotopic TAS2Rs and its relationship with gut functionality and its association with age.
2. To describe the intestinal presence of the human ecnomotopic TAS2Rs in morbid obesity, and their relationship with the changes in the metabolic profile produced by bariatric surgery.
3. To find out the effects on the gut function of the activation of selected intestinal TAS2Rs and their communication with adipose, hepatica and immune tissues.
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Ethics: This project involves ethical aspects.

Workplace location: Campus Sescelades, Tarragona

Gross anual salary:

27103.20 €

Dedication:

Full time

Working hours:

37.5 hours a week

Expected start date:

15 March 2021

European union This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 945413