Title | Proteome Imbalance of Mitochondrial Electron Transport Chain in Brown Adipocytes Leads to Metabolic Benefits. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Masand R, Paulo E, Wu D, Wang Y, Swaney DL, Jimenez-Morales D, Krogan NJ, Wang B |
Journal | Cell Metab |
Volume | 27 |
Issue | 3 |
Pagination | 616-629.e4 |
Date Published | 2018 Mar 06 |
ISSN | 1932-7420 |
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. |
DOI | 10.1016/j.cmet.2018.01.018 |
Alternate Journal | Cell Metab. |
PubMed ID | 29514069 |
PubMed Central ID | PMC6020063 |
Grant List | R01 DK105175 / DK / NIDDK NIH HHS / United States |