Progetto vincitore della Borsa di Studio SISA 2017 - Polito

Evaluation of the effects of ANGPTL3 on cultured adipocytes

Luca Polito

Abstract:

Detection of loss-of-function (LOF) mutations in ANGPTL3 gene in humans revealed the existence of a new lipid phenotype, called familial combined hypolipidemia (FHBL2, OMIM #605019).ANGPLT3 protein is known to be involved in the inhibitory regulation of extracellular lipases (LPL and HL), so that its absence increases the lipolytic degradation of TG-rich lipoproteins (in particular VLDL) and HDL. Accordingly, the FHBL2 status is characterized by markedly reduced levels of all apoB-containing lipoproteins (VLDL and LDL) and HDL.

Interestingly, this condition is also characterized by reduced levels of circulating free fatty acids (FFA).1 This indicates that ANGPTL3 also plays a role in regulating the metabolism of FFA. The molecular mechanisms underlying this action remains unclear. As plasma FFAs are mainly derived from the lipolysis of triglycerides in adipose tissue, our primary hypothesis is that ANGPTL3 regulates lipolytic pathways in adipocytes. The molecular mechanisms underlying the effect of ANGPTL3 on lipolysis in adipose tissue remains largely unclear.

Therefore, the main aim of present study is to investigate changes in lipolytic pathways induced by the addition of ANGPTL3 to 3T3-L1 cell line, an in vitro model of mature adipocytes. Changes in release of FFA and glycerol as well as in cell expression of genes involved in the canonical and non-canonical activation of lipolytic pathways will be investigated by a combination of biochemical measures, Western blot and RT-PCR analyses.
The demonstration that ANGPTL3 influence FFA adipose tissue metabolism would expand the role of this hepatokine in lipid metabolism