IRBETAINE-CIG · Molecular mechanisms underlying the development of insulin resistance: role of betaine supplementation
FP7 — People (Marie Curie Actions)
- Duration
- 2011-09-01 → 2015-08-31
- EU contribution
- €100,000
- Participants
- 2
- Scheme
- MC-CIG
Lines connect the coordinator with its partners.
Results in brief
Periodic Report Summary 1 - IRBETAINE-CIG (Molecular mechanisms underlying the development of insulin resistance: role of betaine supplementation.)
Obesity and diabetes have reached epidemic proportions worldwide. Intensive lifestyle interventions based on diet and exercise have been shown to prevent development of type 2 diabetes in subjects at risk for the disease. While these data are encouraging, these interventions are costly, require a very high degree of commitment of the patients, and are not always successful. Therefore, it is imperative to develop new prevention and treatment strategies. The overall goal of this project is to identify and characterize novel molecular mechanisms underlying the development of diabetes in order to identify specific targets for prevention and therapeutic strategies. For this purpose, we are characterizing the effects of a small metabolite named betaine, which improves glucose balance in a diet induced obese mouse model. We found significant improvements in liver, and in fat tissue after betaine administration. Based on the results from the first period of the grant, we are now working on three different research lines involving the direct effect of betaine in the liver, its function as an osmolyte, and its potential role in gut microbiota in improving host health. This work employs a range of cutting edge technologies including metabolomic analysis and next generation sequencing of mRNA. These powerful tools allow the researcher to evaluate thousands of data points to identify key biomarkers and genetic sequences involved in the development of diabetes and obesity. In collaborations within the host institution, work from this ongoing project is starting to be applied to clinical translational studies in the area of childhood obesity and early nutritional support of preterm infants. The initially funded project has provided the basis for the fellow to establish a productive research group in the host institution, and with the collaborations stemming from this research, provides the fellow with a solid foundation from which he can grow his research agenda and contribute to the scientific community in Europe. More importantly, this work contributes to the body of knowledge identifying early metabolic changes and signals associated with the development of diabetes and obesity, which may ultimately lead to new prevention and treatment strategies and improved population health outcomes.
Data: CORDIS, © European Union
Project objective
Type 2 diabetes (T2D) is a growing global epidemic and new prevention and therapeutic strategies are urgently needed. Insulin resistance is present in high-risk individuals years before the onset of T2D, making the characterization of the complex pathophysiology of insulin resistance a key element of future prevention efforts. The overall goal of our project is to identify and characterize novel molecular mechanisms underlying the development of insulin resistance to find specific targets for prevention and therapeutic strategies.Our analysis of the plasma metabolome of humans at risk for T2D suggests that reductions in betaine levels can contribute to insulin resistance. Consistent with this hypothesis, preliminary studies show that betaine supplementation improves insulin sensitivity and whole-body energy expenditure in a mouse model of diet-induced obesity.First, we propose to determine the mechanisms mediating the beneficial effects of betaine on insulin sensitivity in a diet-induced obese mouse model. For this purpose, C57BL/6 mice will be fed either chow or high-fat diet with or without betaine supplementation. Whole-body and tissue-specific betaine effects will be analyzed to characterize the mechanisms of betaine action. Second, we will apply next generation sequencing of mRNA to analyze the muscle transcriptome associated with high fat feeding and betaine supplementation. As metabolic and molecular changes induced by betaine will be intimately linked to insulin sensitivity, this technique will identify novel genes, alternative splicing isoforms and pathways potentially involved in the development of muscle insulin resistance.This project will constitute a critical first step for future studies aimed at determining whether betaine supplementation is effective in preventing insulin resistance and progression to T2D in humans. Furthermore, it will identify novel targets for designing prevention and therapeutic strategies for the development of T2D.
Original text from CORDIS.
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Data: CORDIS, © European Union