Parkin controls brown adipose tissue plasticity in response to adaptive thermogenesis.

ABSTRACT: Parkin is an ubiquitin-E3 ligase that acts as a key component of the cellular machinery for mitophagy. We show here that Parkin expression is reciprocally regulated in brown adipose tissue in relation to thermogenic activity. Thermogenic stimuli repress Parkin gene expression via transcriptional mechanisms that are elicited by noradrenergic and PPARα-mediated pathways that involve intracellular lipolysis in brown adipocytes. Parkin-KO mice show over-activated brown adipose tissue thermogenic activity and exhibit improved metabolic parameters, especially when fed a high-fat diet. Deacclimation, which is the return of a cold-adapted mouse to a thermoneutral temperature, dramatically induces mitophagy in brown adipocytes, with a concomitant induction of Parkin levels. We further reveal that P

SUBMITTER: Cairo M 

PROVIDER: S-EPMC6501052 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature