All this and more in the full version of our paper: sciencedirect.com/science/arti... (10/11)

Instead, we believe this is mainly caused by a blunted inflammatory response from blocking H1 receptors in the muscle microenvironment and a lowered glucose supply. (9/11)

We then blocked this pathway via administration of H1 and H2 receptor antagonists to humans during and following exercise. Main observation: blocking H1 receptors resulted in an impaired glycogen resynthesis after exercise, independent of canonical insulin signaling. (8/11)

Is this pathway activated by exercise? Yes! We observed a very clear increase in histamine concentration in the muscle interstitial fluid during exercise. And this is a very local phenomenon in the muscle microenvironment, as we did not see a spillover in the circulation (7/11)

Histamine likely signals by being produced in mast cells (via the HDC enzyme) and binding to the specific histamine H1 and H2 receptors that are mainly expressed on myeloid and some vascular cells. (6/11)

By performing some bioinformatic modeling of cellular crosstalk, focused on these mast cells, we obtained new insights into potential signaling networks driven by mast cells. One pathway sparked our interest: histamine signaling from mast cells to myeloid cells (5/11)

This suggested to us that the mononuclear non-muscle cells in skeletal muscle might play a crucial role. We composed a complete cellular profile of skeletal muscle by integrating a single-cell and single-fiber RNA-seq dataset. Look at the small mast cell population! (4/11)

To start this off, we performed transcriptional profiling of exercise effects in bulk muscle (containing many non-muscle cells) versus isolated muscle fibers. Vast effects in bulk muscle were observed (as expected), but this was much more modest in the muscle fibers (3/11)

We previously showed that oral intake of histamine receptor antagonists severely blunts the positive health effects of 6 weeks of exercise training (pubmed.ncbi.nlm.nih.gov/33853781/). We now wanted to take a deep dive into the molecular mechanisms 🧬 (2/11)

Cellular crosstalk in skeletal muscle? A surprising role for mast cells? Histamine as a signal transducer during exercise? Check out the story in @cp-cellmetabolism.bsky.social 🧵

@wimderave.bsky.social, @ugent-fge.bsky.social, @fwovlaanderen.bsky.social

www.sciencedirect.com/science/arti...

Let’s try out this new platform by sharing our recent paper on the transcriptional signatures of individual muscle fibers following high-intensity exercise
#myoblue #myosky

journals.physiology.org/doi/abs/10.1...