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BMBS COST Action BM0602
Adipose Tissue: A Key Target for Prevention of the Metabolic Syndrome

The main objective of the Action is to advance our knowledge on the pathogenesis and prevention

of obesity and the specific role of adipose tissue in the development of the metabolic syndrome.

This approach is driven by the hypothesis that adipose tissue is critically involved in transducing

environmental and nutritional factors into endogenous signals which mediate insulin resistance,

vascular complications, beta cell dysfunction and the manifestation of type 2 diabetes.

To reach the overall goal of this project, a multidisciplinary network will address the following

secondary objectives:

1. Analysis of the central regulation of food intake and adipocyte storage function

The main objective of this part of the Action is to identify new molecular targets that may serve to

control food intake and to prevent the development of the metabolic syndrome. One aim is related

to the elucidation of the links between neuroendocrine dysregulation and adipose tissue secretory

function and inflammation. Specifically, different neuroendocrine systems (cortisol axis, sex

hormones, renin-angiotensin system) will be addressed and their impact for the aetiology of the

metabolic syndrome will be evaluated. An additional specific objective is to promote our

knowledge on glucose sensing systems and their role in the control of energy homeostasis and body

weight. This includes attempts to identify hypothalamic genes with specific function for glucose

sensing. A related aim is to study the dysregulation of hypothalamic nutrient sensing focusing on

fatty acids. Furthermore, it is known that hypothalamic systems involved in energy balance and

appetite regulation are subject to profound gender differences. Specific aims are to identify the

molecular basis of this gender-related difference and its impact for obesity and type 2 diabetes.

Adipose cell size is critically related to glucose tolerance and insulin sensitivity. Therefore, a major

goal is to understand how hypertrophy of adipose cells leads to impaired lipid storage capacity,

impaired adipogenesis and systemic insulin resistance.

2. Elucidation of adipose tissue secretory function

Adipose tissue is considered as a major endocrine organ. Advanced knowledge on this endocrine

activity under normal and pathological conditions is of key importance for developing new

strategies to combat major metabolic diseases related to adipose tissue dysfunction. Therefore, the

main objective of this research task is to comprehensively explore the regulation of adipose tissue

secretory function, the origin of secretory products within the tissue, the actions of these products at

the local and peripheral levels and the pathophysiological relevance for humans. Additional

objectives include the identification of novel secretory products and the investigation of the

pathophysiological role of the adipose tissue and its secretory products in human or animal models

of the metabolic syndrome and type 2 diabetes. Additional attempts will be made to define the

secretory activity of different fat depots and their impact for the aetiology of the metabolic

syndrome. Additional aims are to identify variants of genes coding for adipose secretory products,

an important step towards defining new biomarkers of the metabolic syndrome. Finally, attempts

will be made to better understand plasticity of adipose tissue, which may represent a new approach

to prevention of the metabolic syndrome.

3. Assessment of the relationship between cytokines, inflammation and vascular dysfunction

and skeletal muscle insulin resistance

The combined effects of peripheral insulin resistance and vascular disease is devastating as it

promotes uncontrolled hyperglycemia and damaging effects on peripheral organs and beta cells. It

further promotes endothelial cell dysfunction towards the appearance of pre-atherosclerotic lesions

and overt atherosclerosis accompanied with cardiac complications. One main objective is to

identify the downstream targets of the crosstalk between adipose tissue-derived proinflammatory

cytokines and vascular endothelial and smooth muscle cells. This will be essential to develop new

therapeutic strategies for prevention of the secondary complications associated with the metabolic

syndrome and type 2 diabetes. Attempts will also be made to uncover potential synergistic

interactions between cytokines, hyperglycemia and increased levels of free fatty acids. This

knowledge will help to improve therapeutic measures and patient stratification. A second main

objective is to define the molecular targets involved in the initiation of skeletal muscle insulin

resistance. This knowledge is essential for developing novel drug and life-style intervention

strategies.

4. Gluco-lipotoxcity, islet inflammation, beta cell dysfunction and type 2 diabetes

Multifactorial stressful stimuli are harmful to beta cells and affect their survival and function.

Progressive damage and deterioration of these cells lead to decreased beta cell mass, altered insulin

biosynthesis and impaired glucose-regulated insulin secretion. The main objective is to expand the

current research on glucose- and free fatty acid-induced damage to beta cells to the role of adipose

tissue-derived factors (i.e., proinflammatory cytokines) on the function of beta cells in such adverse

environment. Detailed understanding of the molecular mechanisms that lead to beta cell apoptosis

and dysfunction is essential for developing new strategies to prevent or delay the onset of type 2

diabetes. This knowledge will also help to define new biomarkers that may serve to identify patients

at high risk for developing type 2 diabetes. Another important objective is to investigate and

validate a current hypothesis that some harmful proinflammatory cytokines are produced by beta

cells or islets exposed to hyperglycemia or fatty acids. The differentiation between effects of locally

produced cytokines and adipose-tissue derived cytokines may provide better understanding of beta

cell dysfunction and may lead to selective approaches to ameliorate the harmful consequences of

each.

(Descriptions are provided by the Actions directly via e-COST.)


General Information*

Chair of the Action:

Prof J├╝rgen ECKEL (DE)

Vice Chair of the Action:

Prof Shlomo SASSON (IL)

Science officer of the Action:

Dr Inga DADESHIDZE

Administrative officer of the Action:

Ms Jeannette NCHUNG ORU

Downloads*

Action Fact Sheet

Download AFS as .RTF

Memorandum of Understanding

Download MoU as PDF

Final Report

Download Final Report as PDF

Poster

Download Poster as PDF

Websites*

* content provided by e-COST.
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Last updated: 02 May 2011 top of page