- Mechanisms of adipose tissue dysfunction in obesity: a target of future weight loss strategies for the prevention of diabetes and cardiovascular diseases

https://www.uniupo.it/en/research/research-projects/mechanisms-adipose-tissue-dysfunction-obesity-target-future-weight-loss-strategies-prevention

Funding

Funding body
MUR
Call
PRIN 2017
Budget
106.483 €

Departments and Centres

Departments

DIMET

Department of Translational Medicine

Staff

Project duration

Start date
End date

Energy balance is a fundamental biological process, and revealing the essential mechanisms involved is an ongoing challenge in physiology and research into obesity.
 

The quantity and quality of adipose tissue (AT) are critical issues and influence metabolic and cardiovascular phenotypes in obese patients. The physiopathological factors which trigger obesity complications include altered production patterns of adipokines, lipids and miRNA which accompany the remodelling of dysfunctional AT and adiposopathy (sick fat).

The basis of this phenomenon consists of hypertrophy of adipocytes with inflammation, fibrosity and compromise of function in the vascular structure, adipokines and phenomena of senescence and activation of DNA in response to the damage.

The research network involved in this project includes research laboratories working on the issue of obesity, and aims to transform the foundation and clinical investigation of AT and its functional aspects into new prognostic and therapeutic approaches designed to limit metabolic and cardiovascular risks in patients with obesity, predicting the loss of weight to be achieved by surgical and nutritional measures.
 

The study aims to achieve:

  1. A definition of diagnostic criteria for adiposopathy through a panel of cells, molecules, metabolic, endocrine and inflammation biomarkers of the dysfunction of adipose tissues and the overall cross-sector perspective of clinical evaluations.
  2. An understanding of the predictive role of energy expenditure, measured in a metabolic chamber in eucaloric conditions, and of the hormones involved in metabolic homeostasis in patients selected for bariatric surgery.
  3. A detailed description of the immune infiltration of AT and related synthetic products in relation to T2Dm cases and the level of visceral obesity.
  4. A molecular definition of the role of transcriptome alterations in AT and in the serum in patients with obesity before and after WL, as compared with thin individuals.
  5. Analysis of the role of AT fibrosis related to chronic hypoxia from OSAS in obese individuals (before and after ponderal decrease) who undergo ventilation treatment.
  6. Clinical and lab data on the impact of ponderal decrease on development of T2DM, hypertension, dyslipidemia and adiposopathy.
  7. A correlational study on the morphological data of AT from optical microscope, electronic microscope and immunohistochemistry analysis alongside clinical and metabolic data.

 

The expected results and potential for research expansion include the identification of predictors for progression of obesity towards metabolic and cardiovascular complications.

The research project concentrates on the adipose organ, investigating cellular, molecular, morphological and functional aspects in order to define more clearly adipose dysfunction, taking into consideration basic metabolic changes and comparing dietary treatment with surgical intervention.

The results will be used to develop new therapeutic strategies that, directly or indirectly, could target the adipose organ and thus be considered as a potential treatment for metabolic and cardiovascular anomalies associated with adiposopathy.

Partners of Università del Piemonte Orientale for this project are: Università degli Studi di PADOVA, Università di PISA, Università Politecnica delle MARCHE, Università degli Studi di ROMA "La Sapienza", Università degli Studi di ROMA "Tor Vergata".