Balance maintenance

Researchers co-led by Ludwig Princeton Director Joshua Rabinowitz reported in Nature Metabolism in January that, in mice, homeostasis—or the maintenance of physiologically appropriate balance—for some key circulating metabolites is maintained primarily through their mass-driven consumption, making energy and carbon dioxide, which is exhaled as waste, not through the active regulation of their production or consumption. The researchers administered essential amino acids, serine, alanine, citrate and 3-hydroxybutyrate into the blood of mice and traced their flux—the rise and fall of the molecules and their derivatives—using isotope labelling. An excess of these metabolites did nothing to alter their production. Instead, their consumption ramped up in linear proportion to any excess. This mechanism held across varying conditions—feeding, fasting and high- and low-protein diets—with the breakdown of internal proteins making up amino acid deficits during fasting. The findings indicate that despite the extensive regulatory machinery governing metabolic pathways, mammals achieve circulating metabolite homeostasis primarily through their mass consumption by cells.


This article appeared in the May 2022 issue of Ludwig Link. Click here to download a copy (PDF, 2MB).


You are now leaving Ludwig Cancer Research's website and are going to a website that is not operated by the association. We are not responsible for the content or availability of linked sites. Do you wish to continue?