Increased lipolysis and altered lipid homeostasis protect γ-synuclein-null mutant mice from diet-induced obesity

Steven Millership, Natalia Ninkina, Irina A. Guschina, Jessica Norton, Ricardo Brambilla, Pieter J. Oort, Sean H. Adams, Rowena J. Dennis, Peter J. Voshol, Justin J. Rochford*, Vladimir L. Buchman

*Corresponding author for this work

Research output: Contribution to journalArticle

16 Citations (Scopus)

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 languageEnglish
Pages (from-to)20943-20948
Number of pages6
JournalPNAS
Volume109
Issue number51
Early online date3 Dec 2012
DOIs
Publication statusPublished - 18 Dec 2012

Keywords

  • overexpression
  • gene
  • droplets
  • alpha-synuclein
  • in-vitro
  • adipose triglyceride lipase
  • behavior
  • dopamine
  • resistance
  • mutations

Cite this

Millership, S., Ninkina, N., Guschina, I. A., Norton, J., Brambilla, R., Oort, P. J., Adams, S. H., Dennis, R. J., Voshol, P. J., Rochford, J. J., & Buchman, V. L. (2012). Increased lipolysis and altered lipid homeostasis protect γ-synuclein-null mutant mice from diet-induced obesity. PNAS, 109(51), 20943-20948. https://doi.org/10.1073/pnas.1210022110