Chronic High Phosphate Intake in Mice Affects Macronutrient Utilization and Body Composition

Scope In the last decades, dietary phosphate intake has increased due to a higher consumption of ultraprocessed food. This higher intake has an impact on body composition and health state. Recently, this study finds that a high chronic phosphate diet leads to no major renal alterations, but negatively affects parameters of bone health probably due to the chronic acid load. Here the effect of high phosphate consumption on parameters of energy metabolism is assessed. Methods and Results Healthy mature adult mice are fed for 1 year or 4 months with either a standard (0.6 % w/w) or a high phosphate (1.2 % w/w) diet. Males and females of two different genetic backgrounds are investigated. Mice feed the high phosphate diet show an attenuated body‐weight gain, lower respiratory exchange ratio, decreased body fat mass, and increased lean‐to‐fat mass ratio. Moreover, the high phosphate diet leads to fasting hypoglycemia with no differences in the glucose response to an oral glucose tolerance test. Triglycerides and cholesterol in blood are similar independently of dietary phosphate content. However, 1‐methylhistidine is lower in animals feed a chronic high phosphate intake. Conclusions High phosphate diet attenuates body weight gain, but induces hypoglycemia and may alter muscle homeostasis. Mice fed over one year a two‐fold higher phosphate diet, mimicking the average consumption reported in the general population, showed lower body weight gain and respiratory exchange rate (RER), alterations in body composition, fasting hypoglycemia, and decreased 1‐methylhistidine levels in blood. Previously, we showed that this is accompanied by no major alterations of kidney function, but decreased bone mineral mass.