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Specifically, lipid metabolism in M1 macrophages within lung tissue and the RV is significantly dysregulated: Fatty acid synthase shows elevated expression along with heightened activity in lung tissue, while RV M1 macrophages exhibit elevated CD36-mediated fatty acid uptake, ultimately leading to intracellular fatty acid accumulation and impaired oxidation (83).On the other hand, in the RV tissue of MCT-induced PAH rats, elevated levels of recombinant solute carrier family 1 member 5, glutamine, and glutamate indicate enhanced glutamine metabolism

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The SURPASS-3 MRI substudy added another layer, showing tirzepatide actually reduced muscle fat infiltration across all doses, indicating improved muscle quality even as total muscle volume decreased