Hepatic and renal ketogenesis of hyperpolarized (1-13C)butyrate: functional evidence of metabolic zonation

Ketones bodies are an important metabolic fuel, and butyrate is a ketogenic short-chain fatty acid. We report the metabolism of hyperpolarized (1-13C)butyrate in the rat kidney and liver. The main metabolites in the kidney include [1-13C]acetoacetate, [1-13C]butyrylcarnitine and [5-13C]glutamate, and [1-13C]acetylcarnitine, 3-hydroxy[1-13C]butyrate, [5-13C]citrate and [3-13C]acetoacetate are also detectable. Fasting results in significantly lower butyrylcarnitine/[1-13C]acetoacetate and glutamate/[1-13C]acetoacetate ratios. Ketogenesis is observed in the liver and the [1-13C]butyrylcarnitine + [1-13C]acetoacetate signal normalized to butyrate is higher with fasting. The unexpectedly low 3-hydroxy[1-13C]butyrate signals are functional evidence of metabolic zonation, with acetoacetate production and reduction occurring in different cells.