Millership, Steven, Ninkina, Natalia  ORCID: https://orcid.org/0000-0001-8570-5648, Guschina, Irina, Norton, Jessica, Brambilla, Riccardo ORCID: https://orcid.org/0000-0003-3569-5706, Oort, Pieter J., Adams, Sean H., Dennis, Rowena J., Voshol, Peter J., Rochford, Justin J. and Buchman, Vladimir L. ORCID: https://orcid.org/0000-0002-7631-8352
2012.
Increased lipolysis and altered lipid homeostasis protect γ-synuclein–null mutant mice from diet-induced obesity.
Proceedings of the National Academy of Sciences of the United States of America
109
(51)
, pp. 20943-20948.
10.1073/pnas.1210022110
|
Preview |
PDF
- Published Version
Available under License Creative Commons Attribution. Download (1MB) | Preview |
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.
| Item Type: | Article |
|---|---|
| Date Type: | Publication |
| Status: | Published |
| Schools: | Schools > Biosciences |
| Subjects: | Q Science > QH Natural history > QH301 Biology |
| Publisher: | National Academy of Sciences |
| ISSN: | 0027-8424 |
| Date of First Compliant Deposit: | 30 March 2016 |
| Last Modified: | 10 Oct 2024 16:25 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/49360 |
Citation Data
Cited 23 times in Scopus. View in Scopus. Powered By Scopus® Data
Actions (repository staff only)
 |
Edit Item |
Altmetric
Altmetric