Details

Autor(en) / Beteiligte

• Aboouf, Mostafa A.
• Armbruster, Julia
• Thiersch, Markus
• Gassmann, Max
• Gödecke, Axel
• Gnaiger, Erich
• Kristiansen, Glen
• Bicker, Anne
• Hankeln, Thomas
• Zhu, Hao
• Gorr, Thomas A.

Titel

Myoglobin, expressed in brown adipose tissue of mice, regulates the content and activity of mitochondria and lipid droplets

Ist Teil von

• Biochimica et biophysica acta. Molecular and cell biology of lipids, 2021-12, Vol.1866 (12), p.159026-159026, Article 159026

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• The identification of novel physiological regulators that stimulate energy expenditure through brown adipose tissue (BAT) activity in substrate catalysis is of utmost importance to understand and treat metabolic diseases. Myoglobin (MB), known to store or transport oxygen in heart and skeletal muscles, has recently been found to bind fatty acids with physiological constants in its oxygenated form (i.e., MBO2). Here, we investigated the in vivo effect of MB expression on BAT activity. In particular, we studied mitochondrial function and lipid metabolism as essential determinants of energy expenditure in this tissue. We show in a MB-null (MBko) mouse model that MB expression in BAT impacts on the activity of brown adipocytes in a twofold manner: i) by elevating mitochondrial density plus maximal respiration capacity, and through that, by stimulating BAT oxidative metabolism along with the organelles` uncoupled respiration; and ii) by influencing the free fatty acids pool towards a palmitate-enriched composition and shifting the lipid droplet (LD) equilibrium towards higher counts of smaller droplets. These metabolic changes were accompanied by the up-regulated expression of thermogenesis markers UCP1, CIDEA, CIDEC, PGC1-α and PPAR-α in the BAT of MB wildtype (MBwt) mice. Along with the emergence of the “browning” BAT morphology, MBwt mice exhibited a leaner phenotype when compared to MBko littermates at 20 weeks of age. Our data shed novel insights into MB's role in linking oxygen and lipid-based thermogenic metabolism. The findings suggest potential new strategies of targeting the MB pathway to treat metabolic disorders related to diminishing energy expenditure. [Display omitted] •Myoglobin expression in BAT is induced by cold but not hypoxia.•Myoglobin deficiency reduces mitochondrial respiration and content in BAT.•Myoglobin controls fatty acid composition and lipid droplet morphology in BAT.•Myoglobin deficiency is associated with less abundant thermogenic markers in BAT.•Myoglobin-deficient mice exhibit maturity-onset obesity.