Erythropoietin and long-acting erythropoiesis stimulating agent ameliorate non-alcoholic fatty liver disease by increasing lipolysis and decreasing lipogenesis via EPOR/STAT pathway

Yusuke Tsuma, Jun Mori, Takeshi Ota, Yasuhiro Kawabe, Hidechika Morimoto, Shota Fukuhara, Kazuki Kodo, Atsushi Umemura, Hisakazu Nakajima, Hajime Hosoi

研究成果: Article

抄録

Erythropoietin (EPO) has been reported to exert a beneficial effect on glucose metabolism in obesity. However, the effect of EPO on lipid metabolism and non-alcoholic fatty liver disease (NAFLD) was unclear. Furthermore, the effect of long acting erythropoiesis stimulating agents (ESA) on metabolism has not been poorly understood. The objective of this study was to investigate the effect of EPO and long acting ESA on NAFLD and lipid metabolism. We administered EPO and darbepoetin alpha (DEPO), a long acting ESA, by intraperitoneally injection for 4 weeks to mice with high-fat-diet (HFD)-induced obesity. EPO and DEPO treatment reduced body weight, ameliorated glucose tolerance and insulin resistance, and prevented lipid accumulation in liver and white adipose tissue (WAT). Administration of EPO and DEPO suppressed lipid synthesis-related protein in liver, including sterol regulatory element-binding protein 1 (SREBP-1), acetyl-CoA carboxylase (ACC1) and fatty acid synthase (FAS). EPO and DEPO also increased lipolysis protein in visceral WAT, including hormone-sensitive lipase (HSL), atni-adipose triglyceride lipase (ATGL). EPO and DEPO increased phosphorylation signal transducer and activator of transcription 3 (STAT3) and STAT5, transcriptional factors with crucial roles of lipid metabolism. These data suggest that EPO and DEPO ameliorated NAFLD by improving lipid metabolism via EPO/EPOR-induced STAT3 and STAT5 activation. EPO and DEPO may be a therapeutic option for NAFLD.

元の言語English
ページ(範囲)306-313
ページ数8
ジャーナルBiochemical and Biophysical Research Communications
509
発行部数1
DOI
出版物ステータスPublished - 2019 1 29
外部発表Yes

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Hematinics
Lipogenesis
Lipolysis
Erythropoietin
Liver
Lipid Metabolism
STAT3 Transcription Factor
White Adipose Tissue
Metabolism
Non-alcoholic Fatty Liver Disease
Obesity
Tissue
Sterol Regulatory Element Binding Protein 1
Sterol Esterase
Lipids
Acetyl-CoA Carboxylase
Glucose
Fatty Acid Synthases
Phosphorylation
Intra-Abdominal Fat

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

これを引用

Erythropoietin and long-acting erythropoiesis stimulating agent ameliorate non-alcoholic fatty liver disease by increasing lipolysis and decreasing lipogenesis via EPOR/STAT pathway. / Tsuma, Yusuke; Mori, Jun; Ota, Takeshi; Kawabe, Yasuhiro; Morimoto, Hidechika; Fukuhara, Shota; Kodo, Kazuki; Umemura, Atsushi; Nakajima, Hisakazu; Hosoi, Hajime.

:: Biochemical and Biophysical Research Communications, 巻 509, 番号 1, 29.01.2019, p. 306-313.

研究成果: Article

Tsuma, Yusuke ; Mori, Jun ; Ota, Takeshi ; Kawabe, Yasuhiro ; Morimoto, Hidechika ; Fukuhara, Shota ; Kodo, Kazuki ; Umemura, Atsushi ; Nakajima, Hisakazu ; Hosoi, Hajime. / Erythropoietin and long-acting erythropoiesis stimulating agent ameliorate non-alcoholic fatty liver disease by increasing lipolysis and decreasing lipogenesis via EPOR/STAT pathway. :: Biochemical and Biophysical Research Communications. 2019 ; 巻 509, 番号 1. pp. 306-313.
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abstract = "Erythropoietin (EPO) has been reported to exert a beneficial effect on glucose metabolism in obesity. However, the effect of EPO on lipid metabolism and non-alcoholic fatty liver disease (NAFLD) was unclear. Furthermore, the effect of long acting erythropoiesis stimulating agents (ESA) on metabolism has not been poorly understood. The objective of this study was to investigate the effect of EPO and long acting ESA on NAFLD and lipid metabolism. We administered EPO and darbepoetin alpha (DEPO), a long acting ESA, by intraperitoneally injection for 4 weeks to mice with high-fat-diet (HFD)-induced obesity. EPO and DEPO treatment reduced body weight, ameliorated glucose tolerance and insulin resistance, and prevented lipid accumulation in liver and white adipose tissue (WAT). Administration of EPO and DEPO suppressed lipid synthesis-related protein in liver, including sterol regulatory element-binding protein 1 (SREBP-1), acetyl-CoA carboxylase (ACC1) and fatty acid synthase (FAS). EPO and DEPO also increased lipolysis protein in visceral WAT, including hormone-sensitive lipase (HSL), atni-adipose triglyceride lipase (ATGL). EPO and DEPO increased phosphorylation signal transducer and activator of transcription 3 (STAT3) and STAT5, transcriptional factors with crucial roles of lipid metabolism. These data suggest that EPO and DEPO ameliorated NAFLD by improving lipid metabolism via EPO/EPOR-induced STAT3 and STAT5 activation. EPO and DEPO may be a therapeutic option for NAFLD.",
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T1 - Erythropoietin and long-acting erythropoiesis stimulating agent ameliorate non-alcoholic fatty liver disease by increasing lipolysis and decreasing lipogenesis via EPOR/STAT pathway

AU - Tsuma, Yusuke

AU - Mori, Jun

AU - Ota, Takeshi

AU - Kawabe, Yasuhiro

AU - Morimoto, Hidechika

AU - Fukuhara, Shota

AU - Kodo, Kazuki

AU - Umemura, Atsushi

AU - Nakajima, Hisakazu

AU - Hosoi, Hajime

PY - 2019/1/29

Y1 - 2019/1/29

N2 - Erythropoietin (EPO) has been reported to exert a beneficial effect on glucose metabolism in obesity. However, the effect of EPO on lipid metabolism and non-alcoholic fatty liver disease (NAFLD) was unclear. Furthermore, the effect of long acting erythropoiesis stimulating agents (ESA) on metabolism has not been poorly understood. The objective of this study was to investigate the effect of EPO and long acting ESA on NAFLD and lipid metabolism. We administered EPO and darbepoetin alpha (DEPO), a long acting ESA, by intraperitoneally injection for 4 weeks to mice with high-fat-diet (HFD)-induced obesity. EPO and DEPO treatment reduced body weight, ameliorated glucose tolerance and insulin resistance, and prevented lipid accumulation in liver and white adipose tissue (WAT). Administration of EPO and DEPO suppressed lipid synthesis-related protein in liver, including sterol regulatory element-binding protein 1 (SREBP-1), acetyl-CoA carboxylase (ACC1) and fatty acid synthase (FAS). EPO and DEPO also increased lipolysis protein in visceral WAT, including hormone-sensitive lipase (HSL), atni-adipose triglyceride lipase (ATGL). EPO and DEPO increased phosphorylation signal transducer and activator of transcription 3 (STAT3) and STAT5, transcriptional factors with crucial roles of lipid metabolism. These data suggest that EPO and DEPO ameliorated NAFLD by improving lipid metabolism via EPO/EPOR-induced STAT3 and STAT5 activation. EPO and DEPO may be a therapeutic option for NAFLD.

AB - Erythropoietin (EPO) has been reported to exert a beneficial effect on glucose metabolism in obesity. However, the effect of EPO on lipid metabolism and non-alcoholic fatty liver disease (NAFLD) was unclear. Furthermore, the effect of long acting erythropoiesis stimulating agents (ESA) on metabolism has not been poorly understood. The objective of this study was to investigate the effect of EPO and long acting ESA on NAFLD and lipid metabolism. We administered EPO and darbepoetin alpha (DEPO), a long acting ESA, by intraperitoneally injection for 4 weeks to mice with high-fat-diet (HFD)-induced obesity. EPO and DEPO treatment reduced body weight, ameliorated glucose tolerance and insulin resistance, and prevented lipid accumulation in liver and white adipose tissue (WAT). Administration of EPO and DEPO suppressed lipid synthesis-related protein in liver, including sterol regulatory element-binding protein 1 (SREBP-1), acetyl-CoA carboxylase (ACC1) and fatty acid synthase (FAS). EPO and DEPO also increased lipolysis protein in visceral WAT, including hormone-sensitive lipase (HSL), atni-adipose triglyceride lipase (ATGL). EPO and DEPO increased phosphorylation signal transducer and activator of transcription 3 (STAT3) and STAT5, transcriptional factors with crucial roles of lipid metabolism. These data suggest that EPO and DEPO ameliorated NAFLD by improving lipid metabolism via EPO/EPOR-induced STAT3 and STAT5 activation. EPO and DEPO may be a therapeutic option for NAFLD.

KW - Darbepoetin alpha

KW - Erythropoietin

KW - Lipogenesis

KW - Lipolysis

KW - NAFLD

KW - STAT

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