Myoglobin levels control mitochondrial respiratory capacity in brown adipocytes

Introduction The activation and induction of thermogenesis by brown adipose tissue (BAT) is a potential therapeutic target to treat obesity and its associated metabolic diseases. BAT thermogenesis requires high oxygen and substrate demand. Myoglobin (MB) is highly expressed in BAT and may contribute to oxygen and substrate flux in brown adipocytes.

Research question Do different expression levels of MB expression affect energy metabolism of brown adipocytes?

Methods MB knockdown (KD) was performed in differentiated imBAs by reverse transfection. Primary brown adipocytes were isolated from whole-body MB knock out (KO) mice. MB overexpressing (OE) immortalized brown adipocytes (imBA) were generated by stable transfection. Mitochondrial respiration and cellular responses to adrenergic stimuli were measured and analyzed in fully differentiated MB KD, KO and OE brown adipocytes.

Results MB KD, KO and OE was validated on gene and protein level via qPCR, Western Blot and ELISA. We show that expression levels of MB control brown adipocyte mitochondrial respiratory capacity and acute response to adrenergic stimulation, intracellular cAMP signaling and lipid metabolism. Higher MB expression resulted in increased mitochondrial capacity and responsiveness to adrenergic agonists, with higher lipolysis rates as indicated by an increased release of lactate, free fatty acids and glycerol.

Conclusion Our studies suggest MB as a previously unrecognized player in BAT biology that increases mitochondrial respiratory capacity, a crucial aspect for rapid adaptation to metabolic changes e.g. for thermogenesis. The exact mechanisms of MB contributions, whether by oxygen and/or lipid transport or control of ROS levels remain to be elucidated.

 

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Conflict of Interest

All authors declare that they have no conflict of interest.

Publikationsverlauf

Artikel online veröffentlicht:
26. Mai 2022