Proteomics

Dataset Information

31

Proteome imbalance of mitochondrial electron transport chain in brown adipocytes leads to metabolic benefits


ABSTRACT: Adaptive thermogenesis of brown adipose tissue (BAT) is critical for thermoregulation and contributes to total energy expenditure. However, whether BAT has non-thermogenic functions is largely unknown. Here, we describe that mice with a BAT-specific Liver kinase b1 deletion (Lkb1BKO mice) exhibited impaired mitochondrial respiration and thermogenesis in BAT, but reduced adiposity and liver triglyceride accumulation under high-fat-diet feeding at room temperature. Importantly, these metabolic benefits were also present in Lkb1BKO 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 impaired mitochondrial respiration in BAT of Lkb1BKO 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 tradeoff between BAT thermogenesis and systemic metabolism at both room temperature and thermoneutrality. Collectively, our data demonstrates that ETC proteome imbalance in BAT regulates systemic metabolism independently of BAT thermogenic capacity.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus musculus  

TISSUE(S): Brown Adipose Tissue

DISEASE(S): Not Available

SUBMITTER: Danielle Swaney  

LAB HEAD: Danielle Swaney

PROVIDER: PXD008599 | Pride | 2018-07-12

REPOSITORIES: Pride

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Publications

Proteome Imbalance of Mitochondrial Electron Transport Chain in Brown Adipocytes Leads to Metabolic Benefits.

Masand Ruchi R   Paulo Esther E   Wu Dongmei D   Wang Yangmeng Y   Swaney Danielle L DL   Jimenez-Morales David D   Krogan Nevan J NJ   Wang Biao B  

Cell metabolism 20180301 3


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 (Lkb1BKO) 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 L  ...[more]

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