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

Millership, Steven, Ninkina, Natalia ORCID:, Guschina, Irina, Norton, Jessica, Brambilla, Riccardo ORCID:, Oort, Pieter J., Adams, Sean H., Dennis, Rowena J., Voshol, Peter J., Rochford, Justin J. and Buchman, Vladimir L. ORCID: 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

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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: 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: 04 May 2023 09:19

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