Assessment of mouse liver [1-13C]pyruvate metabolism by dynamic hyperpolarized MRS

Kasper Faarkrog Høyer; Christoffer Laustsen; Steffen Ringgaard; Haiyun Qi; Christian Østergaard Mariager; Thomas Svava Nielsen; Ulrik Kræmer Sundekilde; Jonas T. Treebak; Niels Jessen; Hans Stødkilde-Jørgensen

doi:10.1530/joe-19-0159

Assessment of mouse liver [1-¹³C]pyruvate metabolism by dynamic hyperpolarized MRS

Kasper Faarkrog Høyer, Christoffer Laustsen, Steffen Ringgaard, Haiyun Qi, Christian Østergaard Mariager, Thomas Svava Nielsen, Ulrik Kræmer Sundekilde, Jonas T. Treebak, Niels Jessen, Hans Stødkilde-Jørgensen

2 Citations (Scopus)

Abstract

Hyperpolarized [1-¹³C]pyruvate magnetic resonance (MR) spectroscopy has the unique ability to detect real-time metabolic changes in vivo owing to its high sensitivity compared with thermal MR and high specificity compared with othe r metabolic imaging methods. The aim of this study was to explore the potential of hyperpolarized MR spectroscopy for quantification of liver pyruvate metabolism dur ing a hyperinsulinemic- isoglycemic clamp in mice. Hyperpolarized [1-¹³C]pyruvate was used for in vivo MR spectroscopy of liver pyruvate metabolism in mice. Mice were divided into two groups: (i) non-stimulated 5-h fasted mice and (ii) hyperinsulinemic-isoglycemic clamped mice. During clamp conditions, insulin and donor blood were administered at a constant rate, whereas glucose was infused to maintain isoglycemia. When steady state was reached, insulin-stimulated mice were rapidly infused with hyperpolarized [1-¹³C]pyruvate for real-time tracking of the dynamic distribution of metabolic derivatives from pyruvate, such as [1-¹³C]lactate, [1-¹³C]alanine and [¹³C]bicarbonate. Isotopomer analysis of plasma glucose confirmed ¹³C-incorporation from [1-¹³C]pyruvate into glucose was increased in fasted mice compared with insulin-stimulated mice, demonstrating an increased gluconeogenesis in fasted mice. The AUC ratios for [1-¹³C]alanine/ [1-¹³C]pyruvate (38.2%), [1-¹³C]lactate/[1-¹³C]pyruvate (41.8%) and [¹³C]bicarbonate/ [1-¹³C]pyruvate (169%) all increased significantly during insulin sti mulation. Hyperpolarized [1-¹³C]pyruvate can be used for in vivo MR spectroscopy of liver pyruvate metabolism during hyperinsulinemic-isoglycemic clamp conditions. Under these conditions, insulin decreased gluconeogenesis and increased [1-13C]alanine, [1-13C]lactate and [13C]bicarbonate after a [1-13C]pyruvate bolus. This application of in vivo spectroscopy has the potential to identify impairments in spec ific metabolic pathways in the liver associated with obesity, insulin resistance and nonalcoholic fatty liver disease.

Original language	English
Journal	Journal of Endocrinology
Volume	242
Issue number	3
Pages (from-to)	251-260
Number of pages	9
ISSN	0022-0795
DOIs	https://doi.org/10.1530/joe-19-0159
Publication status	Published - Sept 2019

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@article{8f6e7335a9d440529878dbcca601c853,

title = "Assessment of mouse liver [1-13C]pyruvate metabolism by dynamic hyperpolarized MRS",

abstract = "Hyperpolarized [1-13C]pyruvate magnetic resonance (MR) spectroscopy has the unique ability to detect real-time metabolic changes in vivo owing to its high sensitivity compared with thermal MR and high specificity compared with othe r metabolic imaging methods. The aim of this study was to explore the potential of hyperpolarized MR spectroscopy for quantification of liver pyruvate metabolism dur ing a hyperinsulinemic- isoglycemic clamp in mice. Hyperpolarized [1-13C]pyruvate was used for in vivo MR spectroscopy of liver pyruvate metabolism in mice. Mice were divided into two groups: (i) non-stimulated 5-h fasted mice and (ii) hyperinsulinemic-isoglycemic clamped mice. During clamp conditions, insulin and donor blood were administered at a constant rate, whereas glucose was infused to maintain isoglycemia. When steady state was reached, insulin-stimulated mice were rapidly infused with hyperpolarized [1-13C]pyruvate for real-time tracking of the dynamic distribution of metabolic derivatives from pyruvate, such as [1-13C]lactate, [1-13C]alanine and [13C]bicarbonate. Isotopomer analysis of plasma glucose confirmed 13C-incorporation from [1-13C]pyruvate into glucose was increased in fasted mice compared with insulin-stimulated mice, demonstrating an increased gluconeogenesis in fasted mice. The AUC ratios for [1-13C]alanine/ [1-13C]pyruvate (38.2%), [1-13C]lactate/[1-13C]pyruvate (41.8%) and [13C]bicarbonate/ [1-13C]pyruvate (169%) all increased significantly during insulin sti mulation. Hyperpolarized [1-13C]pyruvate can be used for in vivo MR spectroscopy of liver pyruvate metabolism during hyperinsulinemic-isoglycemic clamp conditions. Under these conditions, insulin decreased gluconeogenesis and increased [1-13C]alanine, [1-13C]lactate and [13C]bicarbonate after a [1-13C]pyruvate bolus. This application of in vivo spectroscopy has the potential to identify impairments in spec ific metabolic pathways in the liver associated with obesity, insulin resistance and nonalcoholic fatty liver disease.",

author = "{Faarkrog H{\o}yer}, Kasper and Christoffer Laustsen and Steffen Ringgaard and Haiyun Qi and Mariager, {Christian {\O}stergaard} and Nielsen, {Thomas Svava} and Sundekilde, {Ulrik Kr{\ae}mer} and Treebak, {Jonas T.} and Niels Jessen and Hans St{\o}dkilde-J{\o}rgensen",

year = "2019",

month = sep,

doi = "10.1530/joe-19-0159",

language = "English",

volume = "242",

pages = "251--260",

journal = "Journal of Endocrinology",

issn = "0022-0795",

publisher = "BioScientifica Ltd.",

number = "3",

}

TY - JOUR

T1 - Assessment of mouse liver [1-13C]pyruvate metabolism by dynamic hyperpolarized MRS

AU - Faarkrog Høyer, Kasper

AU - Laustsen, Christoffer

AU - Ringgaard, Steffen

AU - Qi, Haiyun

AU - Mariager, Christian Østergaard

AU - Nielsen, Thomas Svava

AU - Sundekilde, Ulrik Kræmer

AU - Treebak, Jonas T.

AU - Jessen, Niels

AU - Stødkilde-Jørgensen, Hans

PY - 2019/9

Y1 - 2019/9

N2 - Hyperpolarized [1-13C]pyruvate magnetic resonance (MR) spectroscopy has the unique ability to detect real-time metabolic changes in vivo owing to its high sensitivity compared with thermal MR and high specificity compared with othe r metabolic imaging methods. The aim of this study was to explore the potential of hyperpolarized MR spectroscopy for quantification of liver pyruvate metabolism dur ing a hyperinsulinemic- isoglycemic clamp in mice. Hyperpolarized [1-13C]pyruvate was used for in vivo MR spectroscopy of liver pyruvate metabolism in mice. Mice were divided into two groups: (i) non-stimulated 5-h fasted mice and (ii) hyperinsulinemic-isoglycemic clamped mice. During clamp conditions, insulin and donor blood were administered at a constant rate, whereas glucose was infused to maintain isoglycemia. When steady state was reached, insulin-stimulated mice were rapidly infused with hyperpolarized [1-13C]pyruvate for real-time tracking of the dynamic distribution of metabolic derivatives from pyruvate, such as [1-13C]lactate, [1-13C]alanine and [13C]bicarbonate. Isotopomer analysis of plasma glucose confirmed 13C-incorporation from [1-13C]pyruvate into glucose was increased in fasted mice compared with insulin-stimulated mice, demonstrating an increased gluconeogenesis in fasted mice. The AUC ratios for [1-13C]alanine/ [1-13C]pyruvate (38.2%), [1-13C]lactate/[1-13C]pyruvate (41.8%) and [13C]bicarbonate/ [1-13C]pyruvate (169%) all increased significantly during insulin sti mulation. Hyperpolarized [1-13C]pyruvate can be used for in vivo MR spectroscopy of liver pyruvate metabolism during hyperinsulinemic-isoglycemic clamp conditions. Under these conditions, insulin decreased gluconeogenesis and increased [1-13C]alanine, [1-13C]lactate and [13C]bicarbonate after a [1-13C]pyruvate bolus. This application of in vivo spectroscopy has the potential to identify impairments in spec ific metabolic pathways in the liver associated with obesity, insulin resistance and nonalcoholic fatty liver disease.

AB - Hyperpolarized [1-13C]pyruvate magnetic resonance (MR) spectroscopy has the unique ability to detect real-time metabolic changes in vivo owing to its high sensitivity compared with thermal MR and high specificity compared with othe r metabolic imaging methods. The aim of this study was to explore the potential of hyperpolarized MR spectroscopy for quantification of liver pyruvate metabolism dur ing a hyperinsulinemic- isoglycemic clamp in mice. Hyperpolarized [1-13C]pyruvate was used for in vivo MR spectroscopy of liver pyruvate metabolism in mice. Mice were divided into two groups: (i) non-stimulated 5-h fasted mice and (ii) hyperinsulinemic-isoglycemic clamped mice. During clamp conditions, insulin and donor blood were administered at a constant rate, whereas glucose was infused to maintain isoglycemia. When steady state was reached, insulin-stimulated mice were rapidly infused with hyperpolarized [1-13C]pyruvate for real-time tracking of the dynamic distribution of metabolic derivatives from pyruvate, such as [1-13C]lactate, [1-13C]alanine and [13C]bicarbonate. Isotopomer analysis of plasma glucose confirmed 13C-incorporation from [1-13C]pyruvate into glucose was increased in fasted mice compared with insulin-stimulated mice, demonstrating an increased gluconeogenesis in fasted mice. The AUC ratios for [1-13C]alanine/ [1-13C]pyruvate (38.2%), [1-13C]lactate/[1-13C]pyruvate (41.8%) and [13C]bicarbonate/ [1-13C]pyruvate (169%) all increased significantly during insulin sti mulation. Hyperpolarized [1-13C]pyruvate can be used for in vivo MR spectroscopy of liver pyruvate metabolism during hyperinsulinemic-isoglycemic clamp conditions. Under these conditions, insulin decreased gluconeogenesis and increased [1-13C]alanine, [1-13C]lactate and [13C]bicarbonate after a [1-13C]pyruvate bolus. This application of in vivo spectroscopy has the potential to identify impairments in spec ific metabolic pathways in the liver associated with obesity, insulin resistance and nonalcoholic fatty liver disease.

U2 - 10.1530/joe-19-0159

DO - 10.1530/joe-19-0159

M3 - Journal article

C2 - 31311004

SN - 0022-0795

VL - 242

SP - 251

EP - 260

JO - Journal of Endocrinology

JF - Journal of Endocrinology

IS - 3

ER -