NBR1 is a critical step in the repression of thermogenesis of p62-deficient adipocytes through PPARγ.

TitleNBR1 is a critical step in the repression of thermogenesis of p62-deficient adipocytes through PPARγ.
Publication TypeJournal Article
Year of Publication2021
AuthorsHuang J, Linares JF, Duran A, Xia W, Saltiel AR, Müller TD, Diaz-Meco MT, Moscat J
JournalNat Commun
Date Published2021 05 17
KeywordsAdipocytes, Adipose Tissue, Brown, Animals, Animals, Newborn, Cell Nucleus, Cells, Cultured, Energy Metabolism, HEK293 Cells, Humans, Intracellular Signaling Peptides and Proteins, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, PPAR gamma, Protein Binding, Retinoid X Receptor alpha, Sequestosome-1 Protein, Thermogenesis

Activation of non-shivering thermogenesis is considered a promising approach to lower body weight in obesity. p62 deficiency in adipocytes reduces systemic energy expenditure but its role in sustaining mitochondrial function and thermogenesis remains unresolved. NBR1 shares a remarkable structural similarity with p62 and can interact with p62 through their respective PB1 domains. However, the physiological relevance of NBR1 in metabolism, as compared to that of p62, was not clear. Here we show that whole-body and adipocyte-specific ablation of NBR1 reverts the obesity phenotype induced by p62 deficiency by restoring global energy expenditure and thermogenesis in brown adipose tissue. Impaired adrenergic-induced browning of p62-deficient adipocytes is rescued by NBR1 inactivation, unveiling a negative role of NBR1 in thermogenesis under conditions of p62 loss. We demonstrate that upon p62 inactivation, NBR1 represses the activity of PPARγ, establishing an unexplored p62/NBR1-mediated paradigm in adipocyte thermogenesis that is critical for the control of obesity.

Alternate JournalNat Commun
PubMed ID34001883
PubMed Central IDPMC8129077
Grant ListR01 CA211794 / CA / NCI NIH HHS / United States
R01 CA218254 / CA / NCI NIH HHS / United States
R01 CA246765 / CA / NCI NIH HHS / United States
R01 DK108743 / DK / NIDDK NIH HHS / United States
Related Faculty: 
Jorge Moscat, Ph.D. Juan Francisco Linares Rodriguez, Ph.D. Maria Diaz-Meco Conde, Ph.D. Maria Angeles Duran, Ph.D.

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