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Publication
Metabolic physiology and skeletal muscle phenotypes in male and female myoglobin
knockout mice.
Authors Ono-Moore KD, Olfert IM, Rutkowsky JM, Chintapalli SV, Willis BJ, Blackburn ML,
Williams DK, O'Reilly J, 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 : E63 - E79
PubMed Reference 33969704
Abstract Myoglobin (Mb) is a regulator of O2 bioavailability in type I muscle and heart,
at least when tissue O2 levels drop. Mb also plays a role in regulating cellular
nitric oxide (NO) pools. Robust binding of long-chain fatty acids and long-chain
acylcarnitines to Mb, and enhanced glucose metabolism in hearts of Mb knockout
(KO) mice, suggest additional roles in muscle intermediary metabolism and fuel
selection. To evaluate this hypothesis, we measured energy expenditure (EE),
respiratory exchange ratio (RER), body weight gain and adiposity, glucose
tolerance, and insulin sensitivity in Mb knockout (Mb-/-) and wild-type (WT)
mice challenged with a high-fat diet (HFD, 45% of calories). In males (n =
10/genotype) and females (n = 9/genotype) tested at 5-6, 11-12, and 17-18 wk,
there were no genotype effects on RER, EE, or food intake. RER and EE during
cold (10°C, 72?h), and glucose and insulin tolerance, were not different
compared with within-sex WT controls. At ~18 and ~19 wk of age, female Mb-/-
adiposity was ~42%-48% higher versus WT females (P = 0.1). Transcriptomics
analyses (whole gastrocnemius, soleus) revealed few consistent changes, with the
notable exception of a 20% drop in soleus transferrin receptor (Tfrc) mRNA.
Capillarity indices were significantly increased in Mb-/-, specifically in
Mb-rich soleus and deep gastrocnemius. The results indicate that Mb loss does
not have a major impact on whole body glucose homeostasis, EE, RER, or response
to a cold challenge in mice. However, the greater adiposity in female Mb-/- mice
indicates a sex-specific effect of Mb KO on fat storage and feed efficiency.NEW
& NOTEWORTHY The roles of myoglobin remain to be elaborated. We address sexual
dimorphism in terms of outcomes in response to the loss of myoglobin in knockout
mice and perform, for the first time, a series of comprehensive metabolic
studies under conditions in which fat is mobilized (high-fat diet, cold). The
results highlight that myoglobin is not necessary and sufficient for maintaining
oxidative metabolism and point to alternative roles for this protein in muscle
and heart.




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