Marcus Buschbeck and Lab @marcusbuschbeck.bsky.social · 30/10/20253/7 Mice lacking macroH2A1.1—but not macroH2A1.2 or macroH2A2—developed inflammatory lesions and hyaline casts in kidneys of both sexes, independent of local transcriptomic changes, implicating systemic rather than renal-intrinsic dysfunction. 100
Marcus Buschbeck and Lab @marcusbuschbeck.bsky.social · 30/10/20254/7 This was secondary to a systemic shift in metabolism. Respiratory exchange measurements (RER) indicated reduced oxidation of lipids and increased glucose utilization — consistent with a Warburg-like shift. This was accompanied by alterations in NAD+ metabolism. 100
Marcus Buschbeck and Lab @marcusbuschbeck.bsky.social · 30/10/20255/7 A ketogenic diet, enforcing lipid oxidation and lowering NAD⁺ demand, normalized RER, glucose tolerance, and liver gene profiles, completely preventing kidney abnormalities. Thus, diet overrode the metabolic phenotype associated with macroH2A1.1 loss. 110
