A novel mouse model overexpressing Nocturnin results in decreased fat mass in male mice

Phuong T. Le; Sheila A. Bornstein; Katherine J. Motyl; Li Tian; Jeremy J. Stubblefield; Hee Kyung Hong; Joseph S. Takahashi; Carla B. Green; Clifford J. Rosen; Anyonya R. Guntur

doi:10.1002/jcp.28623

A novel mouse model overexpressing Nocturnin results in decreased fat mass in male mice

Phuong T. Le, Sheila A. Bornstein, Katherine J. Motyl, Li Tian, Jeremy J. Stubblefield, Hee Kyung Hong, Joseph S. Takahashi, Carla B. Green, Clifford J. Rosen, Anyonya R. Guntur^*

^*Corresponding author for this work

Medicine, Endocrinology Division

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

10 Scopus citations

Abstract

Nocturnin (NOCT) belongs to the Mg²⁺ dependent Exonucleases, Endonucleases, Phosphatase (EEP) family of enzymes that exhibit various functions in vitro and in vivo. NOCT is known to function as a deadenylase, cleaving poly-A tails from mRNA (messenger RNA) transcripts. Previously, we reported a role for NOCT in regulating bone marrow stromal cell differentiation through its interactions with PPARγ. In this study, we characterized the skeletal and adipose tissue phenotype when we globally overexpressed Noct in vivo. After 12 weeks of Noct overexpression, transgenic male mice had lower fat mass compared to controls, with no significant differences in the skeleton. Based on the presence of a mitochondrial target sequence in NOCT, we determined that mouse NOCT protein localizes to the mitochondria; subsequently, we found that NOCT overexpression led to a significant increase in the preadipocytes ability to utilize oxidative phosphorylation for ATP (adenosine triphosphate) generation. In summary, the effects of NOCT on adipocytes are likely through its novel role as a mediator of mitochondrial function.

Original language	English (US)
Pages (from-to)	20228-20239
Number of pages	12
Journal	Journal of Cellular Physiology
Volume	234
Issue number	11
DOIs	https://doi.org/10.1002/jcp.28623
State	Published - Nov 2019

Funding

The authors thank Terry Henderson for technical assistance and members of the Rosen lab for critical review of the manuscript. Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Number R03AR068095 to GAR and NIH P50 MH074924, the Silvio O. Conte Center for Neuroscience Research to JST and CBG. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Additional support was provided by the Maine Medical Center Research Institute, Physiology Core which is supported by NIH COBRE in Stem and Progenitor Cell Biology and Regenerative Medicine, P30GM106391 (R. Friesel, PI) and the COBRE in Metabolic Networks P20GM121301 (L. Liaw, PI).

Keywords

Nocturnin
adipogenesis and osteogenesis
bone mass

ASJC Scopus subject areas

Physiology
Clinical Biochemistry
Cell Biology

UN SDGs

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

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10.1002/jcp.28623

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@article{29b4392f49cb499b9a3dc91fa0bff64d,

title = "A novel mouse model overexpressing Nocturnin results in decreased fat mass in male mice",

abstract = "Nocturnin (NOCT) belongs to the Mg2+ dependent Exonucleases, Endonucleases, Phosphatase (EEP) family of enzymes that exhibit various functions in vitro and in vivo. NOCT is known to function as a deadenylase, cleaving poly-A tails from mRNA (messenger RNA) transcripts. Previously, we reported a role for NOCT in regulating bone marrow stromal cell differentiation through its interactions with PPARγ. In this study, we characterized the skeletal and adipose tissue phenotype when we globally overexpressed Noct in vivo. After 12 weeks of Noct overexpression, transgenic male mice had lower fat mass compared to controls, with no significant differences in the skeleton. Based on the presence of a mitochondrial target sequence in NOCT, we determined that mouse NOCT protein localizes to the mitochondria; subsequently, we found that NOCT overexpression led to a significant increase in the preadipocytes ability to utilize oxidative phosphorylation for ATP (adenosine triphosphate) generation. In summary, the effects of NOCT on adipocytes are likely through its novel role as a mediator of mitochondrial function.",

keywords = "Nocturnin, adipogenesis and osteogenesis, bone mass",

author = "Le, {Phuong T.} and Bornstein, {Sheila A.} and Motyl, {Katherine J.} and Li Tian and Stubblefield, {Jeremy J.} and Hong, {Hee Kyung} and Takahashi, {Joseph S.} and Green, {Carla B.} and Rosen, {Clifford J.} and Guntur, {Anyonya R.}",

note = "Funding Information: The authors thank Terry Henderson for technical assistance and members of the Rosen lab for critical review of the manuscript. Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Number R03AR068095 to GAR and NIH P50 MH074924, the Silvio O. Conte Center for Neuroscience Research to JST and CBG. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Additional support was provided by the Maine Medical Center Research Institute, Physiology Core which is supported by NIH COBRE in Stem and Progenitor Cell Biology and Regenerative Medicine, P30GM106391 (R. Friesel, PI) and the COBRE in Metabolic Networks P20GM121301 (L. Liaw, PI). Publisher Copyright: {\textcopyright} 2019 Wiley Periodicals, Inc.",

year = "2019",

month = nov,

doi = "10.1002/jcp.28623",

language = "English (US)",

volume = "234",

pages = "20228--20239",

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AU - Le, Phuong T.

AU - Bornstein, Sheila A.

AU - Motyl, Katherine J.

AU - Tian, Li

AU - Stubblefield, Jeremy J.

AU - Hong, Hee Kyung

AU - Takahashi, Joseph S.

AU - Green, Carla B.

AU - Rosen, Clifford J.

AU - Guntur, Anyonya R.

N1 - Funding Information: The authors thank Terry Henderson for technical assistance and members of the Rosen lab for critical review of the manuscript. Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Number R03AR068095 to GAR and NIH P50 MH074924, the Silvio O. Conte Center for Neuroscience Research to JST and CBG. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Additional support was provided by the Maine Medical Center Research Institute, Physiology Core which is supported by NIH COBRE in Stem and Progenitor Cell Biology and Regenerative Medicine, P30GM106391 (R. Friesel, PI) and the COBRE in Metabolic Networks P20GM121301 (L. Liaw, PI). Publisher Copyright: © 2019 Wiley Periodicals, Inc.

PY - 2019/11

Y1 - 2019/11

N2 - Nocturnin (NOCT) belongs to the Mg2+ dependent Exonucleases, Endonucleases, Phosphatase (EEP) family of enzymes that exhibit various functions in vitro and in vivo. NOCT is known to function as a deadenylase, cleaving poly-A tails from mRNA (messenger RNA) transcripts. Previously, we reported a role for NOCT in regulating bone marrow stromal cell differentiation through its interactions with PPARγ. In this study, we characterized the skeletal and adipose tissue phenotype when we globally overexpressed Noct in vivo. After 12 weeks of Noct overexpression, transgenic male mice had lower fat mass compared to controls, with no significant differences in the skeleton. Based on the presence of a mitochondrial target sequence in NOCT, we determined that mouse NOCT protein localizes to the mitochondria; subsequently, we found that NOCT overexpression led to a significant increase in the preadipocytes ability to utilize oxidative phosphorylation for ATP (adenosine triphosphate) generation. In summary, the effects of NOCT on adipocytes are likely through its novel role as a mediator of mitochondrial function.

AB - Nocturnin (NOCT) belongs to the Mg2+ dependent Exonucleases, Endonucleases, Phosphatase (EEP) family of enzymes that exhibit various functions in vitro and in vivo. NOCT is known to function as a deadenylase, cleaving poly-A tails from mRNA (messenger RNA) transcripts. Previously, we reported a role for NOCT in regulating bone marrow stromal cell differentiation through its interactions with PPARγ. In this study, we characterized the skeletal and adipose tissue phenotype when we globally overexpressed Noct in vivo. After 12 weeks of Noct overexpression, transgenic male mice had lower fat mass compared to controls, with no significant differences in the skeleton. Based on the presence of a mitochondrial target sequence in NOCT, we determined that mouse NOCT protein localizes to the mitochondria; subsequently, we found that NOCT overexpression led to a significant increase in the preadipocytes ability to utilize oxidative phosphorylation for ATP (adenosine triphosphate) generation. In summary, the effects of NOCT on adipocytes are likely through its novel role as a mediator of mitochondrial function.

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ER -

A novel mouse model overexpressing Nocturnin results in decreased fat mass in male mice

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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