Adipocyte NMNAT1 expression is essential for nuclear NAD+ biosynthesis but dispensable for regulating thermogenesis and whole-body energy metabolism

Shintaro Yamaguchi; Daiki Kojima; Tooba Iqbal; Shotaro Kosugi; Michael P. Franczyk; Nathan Qi; Yo Sasaki; Keisuke Yaku; Kenji Kaneko; Kenichiro Kinouchi; Hiroshi Itoh; Kaori Hayashi; Takashi Nakagawa; Jun Yoshino

doi:10.1016/j.bbrc.2023.07.007

Adipocyte NMNAT1 expression is essential for nuclear NAD⁺ biosynthesis but dispensable for regulating thermogenesis and whole-body energy metabolism

Shintaro Yamaguchi, Daiki Kojima, Tooba Iqbal, Shotaro Kosugi, Michael P. Franczyk, Nathan Qi, Yo Sasaki, Keisuke Yaku, Kenji Kaneko, Kenichiro Kinouchi, Hiroshi Itoh, Kaori Hayashi, Takashi Nakagawa, Jun Yoshino^*

^*Corresponding author for this work

Molecular and Medical Pharmacology

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

Nicotinamide adenine dinucleotide (NAD⁺) functions as an essential cofactor regulating a variety of biological processes. The purpose of the present study was to determine the role of nuclear NAD⁺ biosynthesis, mediated by nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1), in thermogenesis and whole-body energy metabolism. We first evaluated the relationship between NMNAT1 expression and thermogenic activity in brown adipose tissue (BAT), a key organ for non-shivering thermogenesis. We found that reduced BAT NMNAT1expression was associated with inactivation of thermogenic gene program induced by obesity and thermoneutrality. Next, we generated and characterized adiponectin-Cre-driven adipocyte-specific Nmnat1 knockout (ANMT1KO) mice. Loss of NMNAT1 markedly reduced nuclear NAD⁺ concentration by approximately 70% in BAT. Nonetheless, adipocyte-specific Nmnat1 deletion had no impact on thermogenic (rectal temperature, BAT temperature and whole-body oxygen consumption) responses to β-adrenergic ligand norepinephrine administration and acute cold exposure, adrenergic-mediated lipolytic activity, and metabolic responses to obesogenic high-fat diet feeding. In addition, loss of NMNAT1 did not affect nuclear lysine acetylation or thermogenic gene program in BAT. These results demonstrate that adipocyte NMNAT1 expression is required for maintaining nuclear NAD⁺ concentration, but not for regulating BAT thermogenesis or whole-body energy homeostasis.

Original language	English
Pages (from-to)	162-169
Number of pages	8
Journal	Biochemical and Biophysical Research Communications
Volume	674
DOIs	https://doi.org/10.1016/j.bbrc.2023.07.007
State	Published - 2023/09/24

Keywords

Adipose tissue
Energy metabolism
NAD
NMNAT1
Nucleus
Thermogenesis

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.bbrc.2023.07.007

Cite this

Yamaguchi, S., Kojima, D., Iqbal, T., Kosugi, S., Franczyk, M. P., Qi, N., Sasaki, Y., Yaku, K., Kaneko, K., Kinouchi, K., Itoh, H., Hayashi, K., Nakagawa, T., & Yoshino, J. (2023). Adipocyte NMNAT1 expression is essential for nuclear NAD⁺ biosynthesis but dispensable for regulating thermogenesis and whole-body energy metabolism. Biochemical and Biophysical Research Communications, 674, 162-169. https://doi.org/10.1016/j.bbrc.2023.07.007

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title = "Adipocyte NMNAT1 expression is essential for nuclear NAD+ biosynthesis but dispensable for regulating thermogenesis and whole-body energy metabolism",

abstract = "Nicotinamide adenine dinucleotide (NAD+) functions as an essential cofactor regulating a variety of biological processes. The purpose of the present study was to determine the role of nuclear NAD+ biosynthesis, mediated by nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1), in thermogenesis and whole-body energy metabolism. We first evaluated the relationship between NMNAT1 expression and thermogenic activity in brown adipose tissue (BAT), a key organ for non-shivering thermogenesis. We found that reduced BAT NMNAT1expression was associated with inactivation of thermogenic gene program induced by obesity and thermoneutrality. Next, we generated and characterized adiponectin-Cre-driven adipocyte-specific Nmnat1 knockout (ANMT1KO) mice. Loss of NMNAT1 markedly reduced nuclear NAD+ concentration by approximately 70% in BAT. Nonetheless, adipocyte-specific Nmnat1 deletion had no impact on thermogenic (rectal temperature, BAT temperature and whole-body oxygen consumption) responses to β-adrenergic ligand norepinephrine administration and acute cold exposure, adrenergic-mediated lipolytic activity, and metabolic responses to obesogenic high-fat diet feeding. In addition, loss of NMNAT1 did not affect nuclear lysine acetylation or thermogenic gene program in BAT. These results demonstrate that adipocyte NMNAT1 expression is required for maintaining nuclear NAD+ concentration, but not for regulating BAT thermogenesis or whole-body energy homeostasis.",

keywords = "Adipose tissue, Energy metabolism, NAD, NMNAT1, Nucleus, Thermogenesis",

author = "Shintaro Yamaguchi and Daiki Kojima and Tooba Iqbal and Shotaro Kosugi and Franczyk, {Michael P.} and Nathan Qi and Yo Sasaki and Keisuke Yaku and Kenji Kaneko and Kenichiro Kinouchi and Hiroshi Itoh and Kaori Hayashi and Takashi Nakagawa and Jun Yoshino",

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doi = "10.1016/j.bbrc.2023.07.007",

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Yamaguchi, S, Kojima, D, Iqbal, T, Kosugi, S, Franczyk, MP, Qi, N, Sasaki, Y, Yaku, K, Kaneko, K, Kinouchi, K, Itoh, H, Hayashi, K, Nakagawa, T & Yoshino, J 2023, 'Adipocyte NMNAT1 expression is essential for nuclear NAD⁺ biosynthesis but dispensable for regulating thermogenesis and whole-body energy metabolism', Biochemical and Biophysical Research Communications, vol. 674, pp. 162-169. https://doi.org/10.1016/j.bbrc.2023.07.007

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T1 - Adipocyte NMNAT1 expression is essential for nuclear NAD+ biosynthesis but dispensable for regulating thermogenesis and whole-body energy metabolism

AU - Yamaguchi, Shintaro

AU - Kojima, Daiki

AU - Iqbal, Tooba

AU - Kosugi, Shotaro

AU - Franczyk, Michael P.

AU - Qi, Nathan

AU - Sasaki, Yo

AU - Yaku, Keisuke

AU - Kaneko, Kenji

AU - Kinouchi, Kenichiro

AU - Itoh, Hiroshi

AU - Hayashi, Kaori

AU - Nakagawa, Takashi

AU - Yoshino, Jun

PY - 2023/9/24

Y1 - 2023/9/24

N2 - Nicotinamide adenine dinucleotide (NAD+) functions as an essential cofactor regulating a variety of biological processes. The purpose of the present study was to determine the role of nuclear NAD+ biosynthesis, mediated by nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1), in thermogenesis and whole-body energy metabolism. We first evaluated the relationship between NMNAT1 expression and thermogenic activity in brown adipose tissue (BAT), a key organ for non-shivering thermogenesis. We found that reduced BAT NMNAT1expression was associated with inactivation of thermogenic gene program induced by obesity and thermoneutrality. Next, we generated and characterized adiponectin-Cre-driven adipocyte-specific Nmnat1 knockout (ANMT1KO) mice. Loss of NMNAT1 markedly reduced nuclear NAD+ concentration by approximately 70% in BAT. Nonetheless, adipocyte-specific Nmnat1 deletion had no impact on thermogenic (rectal temperature, BAT temperature and whole-body oxygen consumption) responses to β-adrenergic ligand norepinephrine administration and acute cold exposure, adrenergic-mediated lipolytic activity, and metabolic responses to obesogenic high-fat diet feeding. In addition, loss of NMNAT1 did not affect nuclear lysine acetylation or thermogenic gene program in BAT. These results demonstrate that adipocyte NMNAT1 expression is required for maintaining nuclear NAD+ concentration, but not for regulating BAT thermogenesis or whole-body energy homeostasis.

AB - Nicotinamide adenine dinucleotide (NAD+) functions as an essential cofactor regulating a variety of biological processes. The purpose of the present study was to determine the role of nuclear NAD+ biosynthesis, mediated by nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1), in thermogenesis and whole-body energy metabolism. We first evaluated the relationship between NMNAT1 expression and thermogenic activity in brown adipose tissue (BAT), a key organ for non-shivering thermogenesis. We found that reduced BAT NMNAT1expression was associated with inactivation of thermogenic gene program induced by obesity and thermoneutrality. Next, we generated and characterized adiponectin-Cre-driven adipocyte-specific Nmnat1 knockout (ANMT1KO) mice. Loss of NMNAT1 markedly reduced nuclear NAD+ concentration by approximately 70% in BAT. Nonetheless, adipocyte-specific Nmnat1 deletion had no impact on thermogenic (rectal temperature, BAT temperature and whole-body oxygen consumption) responses to β-adrenergic ligand norepinephrine administration and acute cold exposure, adrenergic-mediated lipolytic activity, and metabolic responses to obesogenic high-fat diet feeding. In addition, loss of NMNAT1 did not affect nuclear lysine acetylation or thermogenic gene program in BAT. These results demonstrate that adipocyte NMNAT1 expression is required for maintaining nuclear NAD+ concentration, but not for regulating BAT thermogenesis or whole-body energy homeostasis.

KW - Adipose tissue

KW - Energy metabolism

KW - NAD

KW - NMNAT1

KW - Nucleus

KW - Thermogenesis

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DO - 10.1016/j.bbrc.2023.07.007

M3 - 学術論文

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JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

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