The Suv420h histone methyltransferases regulate PPAR-γ and energy expenditure in response to environmental stimuli

Simona Pedrotti, Roberta Caccia, Maria Victoria Neguembor, Jose Manuel Garcia-Manteiga, Giulia Ferri, Clara De Palma, Tamara Canu, Matteo Giovarelli, Paolo Marra, Amleto Fiocchi, Ivan Molineris, Michele Raso, Francesca Sanvito, Claudio Doglioni, Antonio Esposito, Emilio Clementi, Davide Gabellini

Research output: Contribution to journalArticlepeer-review

Abstract

Obesity and its associated metabolic abnormalities have become a global emergency with considerable morbidity and mortality. Epidemiologic and animal model data suggest an epigenetic contribution to obesity. Nevertheless, the cellular and molecular mechanisms through which epigenetics contributes to the development of obesity remain to be elucidated. Suv420h1 and Suv420h2 are histone methyltransferases responsible for chromatin compaction and gene repression. Through in vivo, ex vivo, and in vitro studies, we found that Suv420h1 and Suv420h2 respond to environmental stimuli and regulate metabolism by down-regulating peroxisome proliferator-activated receptor gamma (PPAR-γ), a master transcriptional regulator of lipid storage and glucose metabolism. Accordingly, mice lacking Suv420h proteins activate PPAR-γ target genes in brown adipose tissue to increase mitochondria respiration, improve glucose tolerance, and reduce adipose tissue to fight obesity. We conclude that Suv420h proteins are key epigenetic regulators of PPAR-γ and the pathways controlling metabolism and weight balance in response to environmental stimuli.

Original languageEnglish
Article numbereaav1472
JournalScience Advances
Volume5
Issue number4
DOIs
Publication statusPublished - Jan 1 2019

ASJC Scopus subject areas

  • General
  • Physics and Astronomy (miscellaneous)

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