title: Increased lipolysis and altered lipid homeostasis protect γ-synuclein-null mutant mice from diet-induced obesity.
abstract: Synucleins are a family of homologous proteins principally known for their involvement in neurodegeneration. γ-Synuclein is highly expressed in human white adipose tissue and increased in obesity. Here we show that γ-synuclein is nutritionally regulated in white adipose tissue whereas its loss partially protects mice from high-fat diet (HFD)-induced obesity and ameliorates some of the associated metabolic complications. Compared with HFD-fed WT mice, HFD-fed γ-synuclein-null mutant mice display increased lipolysis, lipid oxidation, and energy expenditure, and reduced adipocyte hypertrophy. Knockdown of γ-synuclein in adipocytes causes redistribution of the key lipolytic enzyme ATGL to lipid droplets and increases lipolysis. γ-Synuclein-deficient adipocytes also contain fewer SNARE complexes of a type involved in lipid droplet fusion. We hypothesize that γ-synuclein may deliver SNAP-23 to the SNARE complexes under lipogenic conditions. Via these independent but complementary roles, γ-synuclein may coordinately modulate lipid storage by influencing lipolysis and lipid droplet formation. Our data reveal γ-synuclein as a regulator of lipid handling in adipocytes, the function of which is particularly important in conditions of nutrient excess.
authors.affiliation: School of Biosciences,  Cardiff University, Cardiff CF10 3AX,  United Kingdom.
authors.forename: Steven
authors.initials: S
authors.lastname: Millership
authors.forename: Natalia
authors.initials: N
authors.lastname: Ninkina
authors.forename: Irina A
authors.initials: IA
authors.lastname: Guschina
authors.forename: Jessica
authors.initials: J
authors.lastname: Norton
authors.forename: Riccardo
authors.initials: R
authors.lastname: Brambilla
authors.forename: Ricardo
authors.initials: R
authors.lastname: Brambilla
authors.forename: Pieter J
authors.initials: PJ
authors.lastname: Oort
authors.forename: Sean H
authors.initials: SH
authors.lastname: Adams
authors.forename: Rowena J
authors.initials: RJ
authors.lastname: Dennis
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Voshol
authors.forename: Justin J
authors.initials: JJ
authors.lastname: Rochford
authors.forename: Vladimir L
authors.initials: VL
authors.lastname: Buchman
mesh_terms: D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D004032:Diet; D005838:Genotype; D008055:Lipids / Q000737:chemistry; D050155:Lipogenesis; D008066:Lipolysis; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D009765:Obesity / Q000378:metabolism*; D051845:gamma-Synuclein
chemical_list: D008055:Lipids; D051845:gamma-Synuclein