TitleProteome Imbalance of Mitochondrial Electron Transport Chain in Brown Adipocytes Leads to Metabolic Benefits.
Publication TypeJournal Article
Year of Publication2018
AuthorsMasand R, Paulo E, Wu D, Wang Y, Swaney DL, Jimenez-Morales D, Krogan NJ, Wang B
JournalCell Metab
Volume27
Issue3
Pagination616-629.e4
Date Published2018 Mar 06
ISSN1932-7420
Abstract

Brown adipose tissue (BAT) thermogenesis is critical for thermoregulation and contributes to total energy expenditure. However, whether BAT has non-thermogenic functions is largely unknown. Here, we describe that BAT-specific liver kinase b1 knockout (Lkb1) mice exhibited impaired BAT mitochondrial respiration and thermogenesis but reduced adiposity and liver triglyceride accumulation under high-fat-diet feeding at room temperature. Importantly, these metabolic benefits were also present in Lkb1 mice at thermoneutrality, where BAT thermogenesis was not required. Mechanistically, decreased mRNA levels of mtDNA-encoded electron transport chain (ETC) subunits and ETC proteome imbalance led to defective BAT mitochondrial respiration in Lkb1 mice. Furthermore, reducing mtDNA gene expression directly in BAT by removing mitochondrial transcription factor A (Tfam) in BAT also showed ETC proteome imbalance and the trade-off between BAT thermogenesis and systemic metabolism at room temperature and thermoneutrality. Collectively, our data demonstrate that ETC proteome imbalance in BAT regulates systemic metabolism independently of thermogenesis.

DOI10.1016/j.cmet.2018.01.018
Alternate JournalCell Metab.
PubMed ID29514069
PubMed Central IDPMC6020063
Grant ListR01 DK105175 / DK / NIDDK NIH HHS / United States