Severe Dietary Zinc Deficiency Does Not Significantly Alter Energy Balance in Adult Mice

Zinc (Zn) is an essential dietary nutrient metal that functions as a cofactor for numerous enzymes involved in diverse cellular processes, including energy metabolism. In humans, Zn deficiency afflicts an estimated one-third of the global population and is a prominent risk factor for numerous diseases, including the development of obesity and diabetes. It is known that severe Zn deficiency leads to impaired growth and development in animals, suggesting that this dietary micronutrient is required for the maintenance of organismal energy balance. However, the impact of Zn restriction on energy balance, specifically energy intake versus expenditure, remains incompletely described in existing murine models of Zn deficiency. Here, we characterized the impact of a prolonged Zn-restricted diet on animal growth, energy balance, and glucose metabolism using metabolic cage analysis and oral glucose tolerance tests in adult mice. While we demonstrated dietary Zn-dependent reductions in body weight with concomitant decreases in energy expenditure and energy intake, we found no significant alterations in energy balance. Furthermore, we observed modest sex-dependent impacts on glucose tolerance. Collectively, these data highlight that prolonged, severe Zn restriction in adult mice does not elicit significant changes in metabolic parameters such as overall energy balance and glucose clearance. These findings indicate that other factors lead to the changes in body weight and composition in Zn-deficient mice.