L-R: Chintan Bhavsar, graduate student in the Nutritional Sciences Graduate Program; Tracy Anthony, professor in the Department of Nutritional Sciences; Loredana Quadro, professor in the Department of Food Science; and Youn-Kyung Kim, associate research scientist in the Quadro lab.
Groundbreaking PNAS research reveals a new pathway regulating vitamin A mobilization from the liver—independent of vitamin A status.
Researchers at Rutgers University have discovered that amino acid scarcity—whether caused by diet or chemotherapy—impairs the liver’s ability to release vitamin A into the bloodstream, revealing a previously unrecognized mechanism for controlling vitamin A availability in the body.
The study, “Amino acid insufficiency impairs hepatic vitamin A mobilization in mice,” was led by Loredana Quadro, professor in the Department of Food Science, and Tracy G. Anthony, professor in the Department of Nutritional Sciences in the Rutgers School of Environmental and Biological Sciences. Chintan Bhavsar, graduate student in the Nutritional Sciences Graduate Program, shares the first co-authorship with Youn-Kyung Kim, post-doc fellow in the Quadro lab. Bhavsar was awarded the 2025 Outstanding Masters Student Award from the Rutgers School of Graduate Studies. Study collaborators include colleagues from the Department of Nutritional Sciences, Department of Food Science, New Jersey Institute for Food Nutrition and Health, and the Rutgers Cancer Institute of New Jersey.
Published in the Proceedings of the National Academy of Sciences (PNAS), the research reveals that amino acid shortage is a novel regulator of vitamin A homeostasis. Using dietary and pharmacological models—including the chemotherapy drug asparaginase—the team found that when amino acids are scarce, the liver accumulates retinol-binding protein 4 (RBP4), the primary vitamin A carrier, while reducing its secretion into the bloodstream.
Vitamin A, which can be obtained through foods or taken as a supplement, including meat and dairy products as well as vegetables and fruits, is an essential nutrient for humans and aids general health, including vision, growth and cell division.
“Our findings challenge the long-held belief that vitamin A distribution is regulated solely by vitamin A status,” said Quadro. “We show that amino acid availability—and the liver’s stress response to it—plays a decisive role in controlling how vitamin A is mobilized to the rest of the body.”
Using mouse models and primary hepatocytes, researchers showed that amino acid insufficiency—whether from a low-protein diet, a leucine-devoid diet, or asparaginase treatment—suppresses secretion of RBP4 and transthyretin (TTR), two key proteins needed for vitamin A transport, without depleting hepatic vitamin A stores. Intriguingly, blocking the autophagy-related gene Atg7 restored normal vitamin A export, pinpointing a critical pathway linking nutrient sensing, protein trafficking and vitamin A metabolism.
“This discovery not only reshapes our understanding of vitamin A biology but could also have important implications for patients with leukemia who are receiving asparaginase, or for those suffering from protein malnutrition, where vitamin A delivery to critical organs like the eye and pancreas may be compromised,” said Anthony.
