Hepatic and renal ketogenesis of hyperpolarized (1-13C)butyrate: functional evidence of metabolic zonation
Hikari A. I. Yoshihara, Rolf Gruetter, Verena Hoerr
Abstract
Hikari A. I. Yoshihara, Rolf Gruetter, Verena Hoerr
Abstract
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.
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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.
Key concepts: Ketogenesis, Butyrate, Ketone bodies, Internal medicine, Endocrinology, Chemistry, Metabolism, Carnitine