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Publication
On the potential role of globins in brown adipose tissue: a novel conceptual
model and studies in myoglobin knockout mice.
Authors Blackburn ML, Wankhade UD, Ono-Moore KD, Chintapalli SV, Fox R, Rutkowsky JM,
Willis BJ, Tolentino T, Lloyd KCK, Adams SH
Submitted By Submitted Externally on 12/3/2021
Status Published
Journal American journal of physiology. Endocrinology and metabolism
Year 2021
Date Published 7/1/2021
Volume : Pages 321 : E47 - E62
PubMed Reference 33969705
Abstract Myoglobin (Mb) regulates O2 bioavailability in muscle and heart as the partial
pressure of O2 (Po2) drops with increased tissue workload. Globin proteins also
modulate cellular NO pools, "scavenging" NO at higher Po2 and converting NO2- to
NO as Po2 falls. Myoglobin binding of fatty acids may also signal a role in fat
metabolism. Interestingly, Mb is expressed in brown adipose tissue (BAT), but
its function is unknown. Herein, we present a new conceptual model that proposes
links between BAT thermogenic activation, concurrently reduced Po2, and NO pools
regulated by deoxy/oxy-globin toggling and xanthine oxidoreductase (XOR). We
describe the effect of Mb knockout (Mb-/-) on BAT phenotype [lipid droplets,
mitochondrial markers uncoupling protein 1 (UCP1) and cytochrome C oxidase 4
(Cox4), transcriptomics] in male and female mice fed a high-fat diet (HFD, 45%
of energy, ~13 wk), and examine Mb expression during brown adipocyte
differentiation. Interscapular BAT weights did not differ by genotype, but there
was a higher prevalence of mid-large sized droplets in Mb-/-. COX4 protein
expression was significantly reduced in Mb-/- BAT, and a suite of
metabolic/NO/stress/hypoxia transcripts were lower. All of these
Mb-/--associated differences were most apparent in females. The new conceptual
model, and results derived from Mb-/- mice, suggest a role for Mb in BAT
metabolic regulation, in part through sexually dimorphic systems and NO
signaling. This possibility requires further validation in light of significant
mouse-to-mouse variability of BAT Mb mRNA and protein abundances in wild-type
mice and lower expression relative to muscle and heart.NEW & NOTEWORTHY
Myoglobin confers the distinct red color to muscle and heart, serving as an
oxygen-binding protein in oxidative fibers. Less attention has been paid to
brown fat, a thermogenic tissue that also expresses myoglobin. In a mouse
knockout model lacking myoglobin, brown fat had larger fat droplets and lower
markers of mitochondrial oxidative metabolism, especially in females. Gene
expression patterns suggest a role for myoglobin as an oxygen/nitric
oxide-sensor that regulates cellular metabolic and signaling pathways.




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