Abstract
Synucleins are a family of homologous proteins principally known for their involvement in neurodegeneration. gamma-Synuclein is highly expressed in human white adipose tissue and increased in obesity. Here we show that gamma-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 gamma-synuclein-null mutant mice display increased lipolysis, lipid oxidation, and energy expenditure, and reduced adipocyte hypertrophy. Knockdown of gamma-synuclein in adipocytes causes redistribution of the key lipolytic enzyme ATGL to lipid droplets and increases lipolysis. gamma-Synuclein-deficient adipocytes also contain fewer SNARE complexes of a type involved in lipid droplet fusion. We hypothesize that gamma-synuclein may deliver SNAP-23 to the SNARE complexes under lipogenic conditions. Via these independent but complementary roles, gamma-synuclein may coordinately modulate lipid storage by influencing lipolysis and lipid droplet formation. Our data reveal gamma-synuclein as a regulator of lipid handling in adipocytes, the function of which is particularly important in conditions of nutrient excess.
Original language | English |
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Pages (from-to) | 20943-20948 |
Number of pages | 6 |
Journal | PNAS |
Volume | 109 |
Issue number | 51 |
Early online date | 3 Dec 2012 |
DOIs | |
Publication status | Published - 18 Dec 2012 |
Keywords
- overexpression
- gene
- droplets
- alpha-synuclein
- in-vitro
- adipose triglyceride lipase
- behavior
- dopamine
- resistance
- mutations