Metabolome in obesity and its co-morbidities, with focus on insulin resistance and type 2- diabetes

Aim and purpose
This project is based on the adipose expandability hypothesis, which states that the link between obesity and metabolic complications does not depend on the total fat mass accumulated, but depends on the remaining capacity for expansion and functioning of the adipose tissue. We hypothesize that the expansion of adipose tissue is associated with lipid remodelling in obesity and its co-morbidities; and that adipocyte membranes are a critical site of early pathophysiological processes leading to insulin resistance and T2D.

The project focuses in applying a metabolomics systems biology approach to improve our etiopathologic understanding of obesity and its co-morbidities, specially insulin resistance and T2D. For this aim, we will characterize the adipose tissue metabolome in progressive stages between health and metabolic disease in unique human clinical studies in order to (1) identify and understand the pathways behind the transition point from health to T2D, and (2) to identify novel circulating biomarkers sensitive to adipose tissue lipid changes. 
In addition, we will develop analytical methodology in the field of lipidomics, with emphasis on complex biological matrices, such as adipose tissue and adipocyte membranes. 


Design and method
The project outline is set up so that we will rely in clinical collaborations to obtain adipose biopsies with matching serum samples in order to study:

  • (Changes in adipose tissue lipidome in non-alcoholic fatty liver disease 
  • Changes in adipose tissue lipidome in bariatric surgery
  • Impact of insulin on adipose tissue and serum metabolites
Comprehensive metabolic analyses using chromatography separation with high resolution mass spectrometry detection platforms (mainly UHPLC-Q-TOFMS for lipidomics, UHPLC-QQQMS for targeted metabolites) will be performed in adipose tissue and matching serum samples.
The metabolic data will be integrated with clinical relevant data by using the systems approach, which will elucidate the key altered lipid pathways in different experimental groups, and predict circulating biomarkers sensitive to adipose tissue-specific changes in obesity comorbidities. 

The predicted biomarkers will be validated based on the lipidomics/metabolomics data from patient matched serum samples.

Target group

Obese subjects with/without type 2 diabetes; with/without NAFLD. 


Expected ending and outcome

Expected ending in December 2019.
The main outcome is to obtain validated early risk biomarkers of co-morbidities associated with obesity that can be translated into clinical practice as early predictive markers of obesity co-morbidities. Thus, the outcomes from this project can be highly valuable for the design of future strategies and interventions for both T2DM treatment and prevention, but also for health promotion.


Collaborators
Prof. Hannele Yki-Järvinen (University of Helsinki, Finland)
Prof. Gertrude Mingrone (Catholic University, School of Medicine, Rome, Italy)
Dr. Marjukka Kohlemainen (University of Eastern Finland, Finland).
Prof. Angela Albarosa Rivellese (University of Naples Federico II, Italy).


Presentations
- 11th annual conference of the Metabolomics Society. Lipidome as a predictive tool in progression to type 2 diabetes in Finnish men (oral presentation), San Francisco (USA), June 29- July 2, 2015.

- Keystone Symposium about Systems Biology of Lipid Metabolism. Lipidome and bile acid profiling to characterise metabolically healthy obesity in weight-discordant monozygotic twins (poster presentation), Breckenridge, Colorado (USA), February 9-13, 2015.

Sidst opdateret 14-02-2017