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NAD metabolism and the SLC34 family: evidence for a liver-kidney axis regulating inorganic phosphate

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Abstract

The solute carrier 34 (SLC34) family of membrane transporters is a major contributor to Pi homeostasis. Many factors are involved in regulating the SLC34 family. The roles of the bone mineral metabolism factors parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) in Pi homeostasis are well studied. Intracellular Pi is thought to be involved in energy metabolism, such as ATP production. Under certain conditions of altered energy metabolism, plasma Pi concentrations are affected by the regulation of a Pi shift into cells or release from the tissues. We recently investigated the mechanism of hepatectomy-related hypophosphatemia, which is thought to involve an unknown phosphaturic factor. Hepatectomy-related hypophosphatemia is due to impaired nicotinamide adenine dinucleotide (NAD) metabolism through its effects on the SLC34 family in the liver-kidney axis. The oxidized form of NAD, NAD+, is an essential cofactor in various cellular biochemical reactions. Levels of NAD+ and its reduced form NADH vary with the availability of dietary energy and nutrients. Nicotinamide phosphoribosyltransferase (Nampt) generates a key NAD+ intermediate, nicotinamide mononucleotide, from nicotinamide and 5-phosphoribosyl 1-pyrophosphate. The liver, an important organ of NAD metabolism, is thought to release metabolic products such as nicotinamide and may control NAD metabolism in other organs. Moreover, NAD is an important regulator of the circadian rhythm. Liver-specific Nampt-deficient mice and heterozygous Nampt mice have abnormal daily plasma Pi concentration oscillations. These data indicate that NAD metabolism in the intestine, liver, and kidney is closely related to Pi metabolism through the SLC34 family. Here, we review the relationship between the SLC34 family and NAD metabolism based on our recent studies.

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Abbreviations

Nampt:

Nicotinamide phosphoribosyltransferase

NAM:

Nicotinamide

NAD+ :

Nicotinamide adenine dinucleotide

MNA:

N1-methylnicotinamide

2-Py:

N1-methyl-2-pyridone-5-carboxamide

4-Py:

N1-methyl-4-pyridine-3-carboxamide

ZT:

Zeitgeber time

PH:

Partial hepatectomy

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Authors and Affiliations

  1. Department of Molecular Nutrition, Institution of Biomedical Science, Tokushima University Graduate School, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan

    Sawako Tatsumi, Ichiro Kaneko, Hiroko Segawa & Ken-ichi Miyamoto

  2. Department of Food Science and Nutrition, School of Human Cultures, The University of Shiga Prefecture, Hikone, Japan

    Sawako Tatsumi

  3. Faculty of Human Life and Science, Department of Food Science and Nutrition, Doshisha Women’s College of Liberal Arts, Kyoto, Japan

    Kanako Katai

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  1. Sawako Tatsumi
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  2. Kanako Katai
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  5. Ken-ichi Miyamoto
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Correspondence to Ken-ichi Miyamoto.

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This article is part of the special issue on Phosphate transport in Pflügers Archiv – European Journal of Physiology

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Tatsumi, S., Katai, K., Kaneko, I. et al. NAD metabolism and the SLC34 family: evidence for a liver-kidney axis regulating inorganic phosphate. Pflugers Arch - Eur J Physiol 471, 109–122 (2019). https://doi.org/10.1007/s00424-018-2204-2

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