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

• Main Author: Millership, Steven James
• Published: Cardiff University 2012
• Subjects: 616.3; QH301 Biology
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.567282

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.