2024/11/28

Could a genetic flaw be the key to stopping people craving sugary treats?

New research has found that people with a genetic defect in how their digestion works eat less cake, sweets and chocolate, which could hold the key to helping the wider population to eat less sugar.

The international study, which is published in Gastroenterology, shows that genetic variations in the sucrase-isomaltase (SI) gene are associated with the intake, and preference, of sucrose-rich foods.

Scientists found that mice lacking the SI gene have a lower intake and preference for dietary sucrose, which develops rapidly and is associated with the inability to regulate appetite hormones. This was confirmed in large population-based cohorts showing that people with genetic defects in sucrose digestion eat fewer cakes, pastries, candy, and chocolate and like foods less as their sucrose content increases.

The work provides novel genetic insights into dietary preferences and opens the possibility of targeting SI to selectively reduce sucrose intake at the population level.

The study was led by Dr. Peter Aldiss, now in the School of Medicine at the University of Nottingham, with co-senior authors Ikerbasque Research Professor Mauro D’Amato from CIC bioGUNE - member of BRTA - and LUM University alongside Dr. Mette K Andersen at the Novo Nordisk Foundation Centre for Basic Metabolic Research.

The team of experts began by investigating the dietary behaviors in mice lacking the SI gene. Here, mice developed a rapid reduction in sucrose intake, and preference. This was confirmed in two large population-based cohorts involving 6,000 individuals in Greenland and 134,766 in the UK Biobank.

The team took a nutrigenetics approach to understand how genetic variation in the SI gene impacts sucrose intake and preference in humans. Strikingly, individuals with a complete inability to digest dietary sucrose in Greenland consumed significantly less sucrose-rich foods whilst individuals with a defective, partially functional SI gene in the UK, liked sucrose-rich foods less.

Dr. Aldiss said: “Excess calories from sugar are an established contributor to obesity and type 2 diabetes. In the UK, we consume 9-12% of our dietary intake from free sugars, such as sucrose, with 79% of the population consuming up to 3 sugary snacks a day. Now, our study suggests that genetic variation in our ability to digest dietary sucrose may impact not only how much sucrose we eat, but how much we like sugary foods, thus opening up the possibility of targeting SI to selectively reduce sucrose intake at the population level.”

We continue to expand our knowledge on the relevance of sucrase-isomaltase to people’s health, as we had previously shown that defective forms of this gene also affect the risk of irritable bowel syndrome (a common functional disorder affecting up to 10% of the population) and the response to its dietary treatment with carbohydrate-reducing diets”, highlighted Professor D’Amato.

In the future, understanding how defects in the SI gene act to reduce the intake, and preference, of dietary sucrose will facilitate the development of novel therapeutics to help curb population-wide sucrose intake to improve digestive and metabolic health, the authors concluded.

The study involved researchers and clinicians from Spain (CIC bioGUNE), Italy (LUM University and University of Naples), Denmark (University of Copenhagen and University of Southern Denmark), Greenland (Steno Diabetes Center and Queen Ingrid's Hospital) and UK (University of Nottingham), and received funding from the Spanish Government MCIN/AEI/10.13039/501100011033 (PCI2021-122064-2A) under the umbrella of the European Joint Programming Initiative “A Healthy Diet for a Healthy Life” (JPI HDHL) and of the ERA-NET Cofund ERA-HDHL (GA N° 696295 of the EU Horizon 2020 Research and Innovation Programme), the Spanish Government MCIN/AEI/10.13039/501100011033 (PID2020-113625RB-I00), Novo Nordisk Foundation (NNF18CC0034900, NNF23SA0084103), the Danish Diabetes Academy (PD005-20) and the NIHR Nottingham Biomedical Research Centre (BRC-1215-20003).

Reference: Peter Aldiss, Leire Torices, Stina Ramne, Marit Eika Jørgensen, Sucrase-Isomaltase Working Group, Mauro D’Amato*, Mette K Andersen*. Sucrase isomaltase dysfunction reduces sucrose intake in mice and humans. Gastroenterology DOI: 10.1053/j.gastro.2024.10.040.

About CIC bioGUNE
The Centre for Cooperative Research in Biosciences (CIC bioGUNE), member of the Basque Research & Technology Alliance (BRTA), located in the Bizkaia Technology Park, is a biomedical research organisation conducting cutting-edge research at the interface between structural, molecular and cell biology, with a particular focus on generating knowledge on the molecular bases of disease, for use in the development of new diagnostic methods and advanced therapies.

About Ikerbasque
Ikerbasque - Basque Foundation for Science - is the result of an initiative of the Department of Education of the Basque Government that aims to reinforce the commitment to scientific research by attracting, recovering and consolidating excellent researchers from all over the world. Currently, it is a consolidated organization that has 290 researchers/s, who develop their work in all fields of knowledge.

About BRTA
BRTA is an alliance of 4 collaborative research centres (CIC bioGUNE, CIC nanoGUNE, CIC biomaGUNE y CIC energiGUNE) and 13 technology centres (Azterlan, Azti, Ceit, Cidetec, Gaiker, Ideko, Ikerlan, Leartiker, Lortek, Neiker, Tecnalia, Tekniker y Vicomtech) with the main objective of developing advanced technological solutions for the Basque corporate fabric.

With the support of the Basque Government, the SPRI Group and the Provincial Councils of the three territories, the alliance seeks to promote collaboration between the research centres, strengthen the conditions to generate and transfer knowledge to companies, contributing to their competitiveness and outspreading the Basque scientific-technological capacity abroad.

BRTA has a workforce of 3,500 professionals, executes 22% of the Basque Country's R&D investment, registers an annual turnover of more than 300 million euros and generates 100 European and international patents per year.

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