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Title: Gamma-synuclein, a novel player in the control of body lipid metabolism
Author: Millership, Steven James
ISNI:       0000 0004 2733 1627
Awarding Body: Cardiff University
Current Institution: Cardiff University
Date of Award: 2012
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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.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QH301 Biology