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Role of new G-protein coupled receptors on adipogenesis, lipolysis and adipokine secretion in white adipocytes: functional and genetic studies.

Topicality

Adipose tissue is an important regulator of metabolism in human organism and act as an endocrine organ. Adipose tissue produces a variety of bioactive molecules, adipokines, that regulate functions of the organism that are closely related to adiposity, cardiovascular diseases, type 2 diabetes and hypertension. G protein coupled receptors (GPCRs) play a crucial role in adipocyte function. Recently, several orphan GPCRs have been discovered in adipocytes, but their functional role still remains elusive. Elucidation of signaling and functional activities of these novel GPCRs will likely lead to new and improved therapeutics against lipid disorders and coronary heart disease.

Aim

Investigation of functional, genetic and structural aspects of four recently discovered GPCRs (GPR43, GPR109A, GPR109B and GPR81) in white fat cells.

Tasks

1)             Detect polymorphisms in GPR43, GPR109A, GPR109B and GPR81 gene loci and analyse their possible association with lipid metabolism disorders, biochemical parameters and adipokine profiles in samples from Latvian Genome Data Base (LGDB).

2)             Investigate ligand- receptor and receptor- receptor interactions (homo- and hetero-dimerization) and their functional role in mammalian and yeast cell cultures expressing recombinant GPR43, GPR109A, GPR109B and GPR81.

3)             Elucidate the potentional role of previously mentioned GPCRs in adipogenesis, lipogenesis, lipolysis and adipokine secretion in pre-adipocyte and adipocyte cell cultures treated with selective ligands.

Planned results

1)             Identification of four gene loci association with different phenotypic traits and possible discovery of novel genetic markers for adiposity, diabetes and cardiovascular disease risks.

2)             Characterisation of possible ligand- receptor and receptor- receptor interaction mechanisms and their impact on receptor signaling and adipocyte function.

3)             Revealing the role of GPCRs in adipogenesis, lipolysis, and adipokine expression and secretion.



Mājas lapas izstrādi finansēja ERAF 2.1.1.2. aktivitātes projekts Nr. 2010/0196/2DP/2.1.1.2.0/10/APIA/VIAA/004 "Latvijas biomedicīnas pētījumu integrācija Eiropas zinātnes telpā".