Depletion of Prmt1 in Adipocytes Impairs Glucose Homeostasis in Diet-Induced Obesity

Seri Choi; Dahee Choi; Yun Kyung Lee; Seung Hyun Ahn; Je Kyung Seong; Sung Wook Chi; Tae Jung Oh; Sung Hee Choi; Seung Hoi Koo

doi:10.2337/DB20-1050

Depletion of Prmt1 in Adipocytes Impairs Glucose Homeostasis in Diet-Induced Obesity

Seri Choi, Dahee Choi, Yun Kyung Lee, Seung Hyun Ahn, Je Kyung Seong, Sung Wook Chi, Tae Jung Oh, Sung Hee Choi, Seung Hoi Koo

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Abstract

Protein arginine methyltransferase (PRMT) 1 is involved in the regulation of various metabolic pathways such as glucose metabolism in liver and atrophy in the skeletal muscle. However, the role of PRMT1 in the fat tissues under the disease state has not been elucidated to date. In this study, we delineate the function of this protein in adipocytes in vivo. PRMT1 expression was abundant in the white adipose tissues (WAT), which was induced upon a high-fat diet in mice and by obesity in humans. We found that adipocyte-specific depletion of Prmt1 resulted in decreased fat mass without overall changes in body weight in mice. Mechanistically, the depletion of Prmt1 in WAT led to the activation of the AMPK pathway, which was causal to the increased lipophagy, mitochondrial lipid catabolism, and the resultant reduction in lipid droplet size in WAT in vivo. Interestingly, despite the increased energy expenditure, we observed a promotion of adipose tissue inflammation and an ectopic accumulation of triglycerides in the peripheral tissues in Prmt1 adipocyte-specific knockout mice, which promoted the impaired insulin tolerance that is reminiscent of mouse models of lipodystrophy. These data collectively suggest that PRMT1 prevents WAT from excessive degradation of triglycerides by limiting AMPK-mediated lipid catabolism to control whole-body metabolic homeostasis in diet-induced obesity conditions.

Original language	English
Pages (from-to)	1664-1678
Number of pages	15
Journal	Diabetes
Volume	70
Issue number	8
DOIs	https://doi.org/10.2337/DB20-1050
Publication status	Published - 2021 Aug

Bibliographical note

Funding Information:
Acknowledgments. The authors thank Dr. Chul-Ho Lee (Korea Research Institute of Bioscience & Biotechnology) for providing adiponectin-Cre transgenic mice. Funding. This research was supported by the National Research Foundation of Korea grants funded by the Korean Government (MSIT) (NRF-2018R1A2B3001540, NRF-2015R1A5A1009024, NRF-2019M3A9D5A01102794, and NRF-2021R1A2C30 03435). S.C. was supported by NRF-2019R1A6A3A01096171, and S.W.C. was supported by NRF-2016R1C1B2014390. S.-H.K. was also supported by a grant from Korea University. Duality of Interest. No potential conflicts of interest relevant to this article were reported. Author Contributions. S.C., D.C., and Y.-K.L. performed experiments. S.C., J.K.S., S.W.C., T.J.O., S.H.C., and S.-H.K. interpreted data. S.C. and S.-H.K. conceived the idea and developed the study design. S.C. and S.-H.K. wrote the manuscript. S.H.A. and S.W.C. analyzed the RNA sequencing data. S.-H.K. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Publisher Copyright:
© 2021 by the American Diabetes Association.

ASJC Scopus subject areas

Internal Medicine
Endocrinology, Diabetes and Metabolism

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10.2337/DB20-1050

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title = "Depletion of Prmt1 in Adipocytes Impairs Glucose Homeostasis in Diet-Induced Obesity",

abstract = "Protein arginine methyltransferase (PRMT) 1 is involved in the regulation of various metabolic pathways such as glucose metabolism in liver and atrophy in the skeletal muscle. However, the role of PRMT1 in the fat tissues under the disease state has not been elucidated to date. In this study, we delineate the function of this protein in adipocytes in vivo. PRMT1 expression was abundant in the white adipose tissues (WAT), which was induced upon a high-fat diet in mice and by obesity in humans. We found that adipocyte-specific depletion of Prmt1 resulted in decreased fat mass without overall changes in body weight in mice. Mechanistically, the depletion of Prmt1 in WAT led to the activation of the AMPK pathway, which was causal to the increased lipophagy, mitochondrial lipid catabolism, and the resultant reduction in lipid droplet size in WAT in vivo. Interestingly, despite the increased energy expenditure, we observed a promotion of adipose tissue inflammation and an ectopic accumulation of triglycerides in the peripheral tissues in Prmt1 adipocyte-specific knockout mice, which promoted the impaired insulin tolerance that is reminiscent of mouse models of lipodystrophy. These data collectively suggest that PRMT1 prevents WAT from excessive degradation of triglycerides by limiting AMPK-mediated lipid catabolism to control whole-body metabolic homeostasis in diet-induced obesity conditions.",

author = "Seri Choi and Dahee Choi and Lee, {Yun Kyung} and Ahn, {Seung Hyun} and Seong, {Je Kyung} and Chi, {Sung Wook} and Oh, {Tae Jung} and Choi, {Sung Hee} and Koo, {Seung Hoi}",

note = "Funding Information: Acknowledgments. The authors thank Dr. Chul-Ho Lee (Korea Research Institute of Bioscience & Biotechnology) for providing adiponectin-Cre transgenic mice. Funding. This research was supported by the National Research Foundation of Korea grants funded by the Korean Government (MSIT) (NRF-2018R1A2B3001540, NRF-2015R1A5A1009024, NRF-2019M3A9D5A01102794, and NRF-2021R1A2C30 03435). S.C. was supported by NRF-2019R1A6A3A01096171, and S.W.C. was supported by NRF-2016R1C1B2014390. S.-H.K. was also supported by a grant from Korea University. Duality of Interest. No potential conflicts of interest relevant to this article were reported. Author Contributions. S.C., D.C., and Y.-K.L. performed experiments. S.C., J.K.S., S.W.C., T.J.O., S.H.C., and S.-H.K. interpreted data. S.C. and S.-H.K. conceived the idea and developed the study design. S.C. and S.-H.K. wrote the manuscript. S.H.A. and S.W.C. analyzed the RNA sequencing data. S.-H.K. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Publisher Copyright: {\textcopyright} 2021 by the American Diabetes Association.",

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doi = "10.2337/DB20-1050",

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AU - Choi, Dahee

AU - Lee, Yun Kyung

AU - Ahn, Seung Hyun

AU - Seong, Je Kyung

AU - Chi, Sung Wook

AU - Oh, Tae Jung

AU - Choi, Sung Hee

AU - Koo, Seung Hoi

N1 - Funding Information: Acknowledgments. The authors thank Dr. Chul-Ho Lee (Korea Research Institute of Bioscience & Biotechnology) for providing adiponectin-Cre transgenic mice. Funding. This research was supported by the National Research Foundation of Korea grants funded by the Korean Government (MSIT) (NRF-2018R1A2B3001540, NRF-2015R1A5A1009024, NRF-2019M3A9D5A01102794, and NRF-2021R1A2C30 03435). S.C. was supported by NRF-2019R1A6A3A01096171, and S.W.C. was supported by NRF-2016R1C1B2014390. S.-H.K. was also supported by a grant from Korea University. Duality of Interest. No potential conflicts of interest relevant to this article were reported. Author Contributions. S.C., D.C., and Y.-K.L. performed experiments. S.C., J.K.S., S.W.C., T.J.O., S.H.C., and S.-H.K. interpreted data. S.C. and S.-H.K. conceived the idea and developed the study design. S.C. and S.-H.K. wrote the manuscript. S.H.A. and S.W.C. analyzed the RNA sequencing data. S.-H.K. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Publisher Copyright: © 2021 by the American Diabetes Association.

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N2 - Protein arginine methyltransferase (PRMT) 1 is involved in the regulation of various metabolic pathways such as glucose metabolism in liver and atrophy in the skeletal muscle. However, the role of PRMT1 in the fat tissues under the disease state has not been elucidated to date. In this study, we delineate the function of this protein in adipocytes in vivo. PRMT1 expression was abundant in the white adipose tissues (WAT), which was induced upon a high-fat diet in mice and by obesity in humans. We found that adipocyte-specific depletion of Prmt1 resulted in decreased fat mass without overall changes in body weight in mice. Mechanistically, the depletion of Prmt1 in WAT led to the activation of the AMPK pathway, which was causal to the increased lipophagy, mitochondrial lipid catabolism, and the resultant reduction in lipid droplet size in WAT in vivo. Interestingly, despite the increased energy expenditure, we observed a promotion of adipose tissue inflammation and an ectopic accumulation of triglycerides in the peripheral tissues in Prmt1 adipocyte-specific knockout mice, which promoted the impaired insulin tolerance that is reminiscent of mouse models of lipodystrophy. These data collectively suggest that PRMT1 prevents WAT from excessive degradation of triglycerides by limiting AMPK-mediated lipid catabolism to control whole-body metabolic homeostasis in diet-induced obesity conditions.

AB - Protein arginine methyltransferase (PRMT) 1 is involved in the regulation of various metabolic pathways such as glucose metabolism in liver and atrophy in the skeletal muscle. However, the role of PRMT1 in the fat tissues under the disease state has not been elucidated to date. In this study, we delineate the function of this protein in adipocytes in vivo. PRMT1 expression was abundant in the white adipose tissues (WAT), which was induced upon a high-fat diet in mice and by obesity in humans. We found that adipocyte-specific depletion of Prmt1 resulted in decreased fat mass without overall changes in body weight in mice. Mechanistically, the depletion of Prmt1 in WAT led to the activation of the AMPK pathway, which was causal to the increased lipophagy, mitochondrial lipid catabolism, and the resultant reduction in lipid droplet size in WAT in vivo. Interestingly, despite the increased energy expenditure, we observed a promotion of adipose tissue inflammation and an ectopic accumulation of triglycerides in the peripheral tissues in Prmt1 adipocyte-specific knockout mice, which promoted the impaired insulin tolerance that is reminiscent of mouse models of lipodystrophy. These data collectively suggest that PRMT1 prevents WAT from excessive degradation of triglycerides by limiting AMPK-mediated lipid catabolism to control whole-body metabolic homeostasis in diet-induced obesity conditions.

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Depletion of Prmt1 in Adipocytes Impairs Glucose Homeostasis in Diet-Induced Obesity

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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