Gamma-synuclein, a novel player in the control of body lipid metabolism

Millership, Steven James 2012. Gamma-synuclein, a novel player in the control of body lipid metabolism. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

Synucleins are a family of homologous, predominantly neuronal proteins known for their involvement in neurodegeneration. In neurons α-synuclein promotes the assembly of soluble-NSF-attachment receptor (SNARE) complexes required for fusion of synaptic vesicles with the plasma membrane during neurotransmitter release. γ-synuclein is highly expressed in human white adipose tissue (WAT) and this expression is increased in obesity. Here we show that γ-synuclein is nutritionally regulated in murine adipocytes and that γ-synuclein deficiency protects mice from high fat diet (HFD)-induced obesity and associated metabolic complications. When compared to HFD-fed wild type mice, HFD-fed γ-synuclein deficient mice display increased lipolysis, lipid oxidation and energy expenditure, and reduced adipocyte hypertrophy. γ-synuclein null adipocytes express more ATGL, a key lipolytic enzyme, and contain fewer SNARE complexes of a type involved in lipid droplet fusion. Thus, γ-synuclein may co-ordinately affect both lipid droplet formation and lipid hydrolysis. We also find that γ-synuclein deficiency causes alterations in lipid classes and fatty acid patterns in the adult murine brain. Together our data suggest that γ-synuclein is a novel regulator of lipid handling in both CNS neurons and adipocytes, with this adipocyte function becoming particularly important in conditions of nutrient excess.

Item Type:	Thesis (PhD)
Status:	Unpublished
Schools:	Schools > Biosciences
Subjects:	Q Science > QH Natural history > QH301 Biology
Uncontrolled Keywords:	synucleins, lipid, metabolism, SNARE, adipocyte
Date of First Compliant Deposit:	30 March 2016
Last Modified:	19 Mar 2016 22:45
URI:	https://orca.cardiff.ac.uk/id/eprint/26009

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