Skip to main content

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

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.

Call for proposal

FP7-PEOPLE-2011-CIG
See other projects for this call

Funding Scheme

MC-CIG - Support for training and career development of researcher (CIG)

Coordinator

FUNDACIO SANT JOAN DE DEU
Address
Calle Santa Rosa, 39-57
08950 Esplugues De Llobregat
Spain
Activity type
Research Organisations
EU contribution
€ 53 158,60
Administrative Contact
Roser Arnalte (Mrs.)

Participants (1)

CONSORCI INSTITUT D'INVESTIGACIONS BIOMEDIQUES AUGUST PI I SUNYER

Participation ended

Spain
EU contribution
€ 46 841,40
Address
Calle Rossello 149 Puerta Bjs
08036 Barcelona
Activity type
Other
Administrative Contact
Sara Hurst (Ms.)