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Molecular mechanisms underlying the development of insulin resistance: role of betaine supplementation

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.