Treatment with atrial natriuretic peptide induces adipose tissue browning and exerts thermogenic actions in vivo

Abstract Increasing evidence suggests natriuretic peptides (NPs) coordinate inter-organ metabolic crosstalk with adipose tissues and play a critical role in energy metabolism. We recently reported A-type NP (ANP) raises intracellular temperature in cultured adipocytes in a low-temperature-sensitive...

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Main Authors: Haruka Kimura, Tomohisa Nagoshi, Yuhei Oi, Akira Yoshii, Yoshiro Tanaka, Hirotake Takahashi, Yusuke Kashiwagi, Toshikazu D. Tanaka, Michihiro Yoshimura
Format: Article
Language:English
Published: Nature Portfolio 2021-08-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-021-96970-9
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author Haruka Kimura
Tomohisa Nagoshi
Yuhei Oi
Akira Yoshii
Yoshiro Tanaka
Hirotake Takahashi
Yusuke Kashiwagi
Toshikazu D. Tanaka
Michihiro Yoshimura
author_facet Haruka Kimura
Tomohisa Nagoshi
Yuhei Oi
Akira Yoshii
Yoshiro Tanaka
Hirotake Takahashi
Yusuke Kashiwagi
Toshikazu D. Tanaka
Michihiro Yoshimura
author_sort Haruka Kimura
collection DOAJ
description Abstract Increasing evidence suggests natriuretic peptides (NPs) coordinate inter-organ metabolic crosstalk with adipose tissues and play a critical role in energy metabolism. We recently reported A-type NP (ANP) raises intracellular temperature in cultured adipocytes in a low-temperature-sensitive manner. We herein investigated whether exogenous ANP-treatment exerts a significant impact on adipose tissues in vivo. Mice fed a high-fat-diet (HFD) or normal-fat-diet (NFD) for 13 weeks were treated with or without ANP infusion subcutaneously for another 3 weeks. ANP-treatment significantly ameliorated HFD-induced insulin resistance. HFD increased brown adipose tissue (BAT) cell size with the accumulation of lipid droplets (whitening), which was suppressed by ANP-treatment (re-browning). Furthermore, HFD induced enlarged lipid droplets in inguinal white adipose tissue (iWAT), crown-like structures in epididymal WAT, and hepatic steatosis, all of which were substantially attenuated by ANP-treatment. Likewise, ANP-treatment markedly increased UCP1 expression, a specific marker of BAT, in iWAT (browning). ANP also further increased UCP1 expression in BAT with NFD. Accordingly, cold tolerance test demonstrated ANP-treated mice were tolerant to cold exposure. In summary, exogenous ANP administration ameliorates HFD-induced insulin resistance by attenuating hepatic steatosis and by inducing adipose tissue browning (activation of the adipose tissue thermogenic program), leading to in vivo thermogenesis during cold exposure.
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spelling doaj.art-df6b1060b76d4735a8324161aae50b392022-12-21T22:43:03ZengNature PortfolioScientific Reports2045-23222021-08-0111111110.1038/s41598-021-96970-9Treatment with atrial natriuretic peptide induces adipose tissue browning and exerts thermogenic actions in vivoHaruka Kimura0Tomohisa Nagoshi1Yuhei Oi2Akira Yoshii3Yoshiro Tanaka4Hirotake Takahashi5Yusuke Kashiwagi6Toshikazu D. Tanaka7Michihiro Yoshimura8Division of Cardiology, Department of Internal Medicine, The Jikei University School of MedicineDivision of Cardiology, Department of Internal Medicine, The Jikei University School of MedicineDivision of Cardiology, Department of Internal Medicine, The Jikei University School of MedicineDivision of Cardiology, Department of Internal Medicine, The Jikei University School of MedicineDivision of Cardiology, Department of Internal Medicine, The Jikei University School of MedicineDivision of Cardiology, Department of Internal Medicine, The Jikei University School of MedicineDivision of Cardiology, Department of Internal Medicine, The Jikei University School of MedicineDivision of Cardiology, Department of Internal Medicine, The Jikei University School of MedicineDivision of Cardiology, Department of Internal Medicine, The Jikei University School of MedicineAbstract Increasing evidence suggests natriuretic peptides (NPs) coordinate inter-organ metabolic crosstalk with adipose tissues and play a critical role in energy metabolism. We recently reported A-type NP (ANP) raises intracellular temperature in cultured adipocytes in a low-temperature-sensitive manner. We herein investigated whether exogenous ANP-treatment exerts a significant impact on adipose tissues in vivo. Mice fed a high-fat-diet (HFD) or normal-fat-diet (NFD) for 13 weeks were treated with or without ANP infusion subcutaneously for another 3 weeks. ANP-treatment significantly ameliorated HFD-induced insulin resistance. HFD increased brown adipose tissue (BAT) cell size with the accumulation of lipid droplets (whitening), which was suppressed by ANP-treatment (re-browning). Furthermore, HFD induced enlarged lipid droplets in inguinal white adipose tissue (iWAT), crown-like structures in epididymal WAT, and hepatic steatosis, all of which were substantially attenuated by ANP-treatment. Likewise, ANP-treatment markedly increased UCP1 expression, a specific marker of BAT, in iWAT (browning). ANP also further increased UCP1 expression in BAT with NFD. Accordingly, cold tolerance test demonstrated ANP-treated mice were tolerant to cold exposure. In summary, exogenous ANP administration ameliorates HFD-induced insulin resistance by attenuating hepatic steatosis and by inducing adipose tissue browning (activation of the adipose tissue thermogenic program), leading to in vivo thermogenesis during cold exposure.https://doi.org/10.1038/s41598-021-96970-9
spellingShingle Haruka Kimura
Tomohisa Nagoshi
Yuhei Oi
Akira Yoshii
Yoshiro Tanaka
Hirotake Takahashi
Yusuke Kashiwagi
Toshikazu D. Tanaka
Michihiro Yoshimura
Treatment with atrial natriuretic peptide induces adipose tissue browning and exerts thermogenic actions in vivo
Scientific Reports
title Treatment with atrial natriuretic peptide induces adipose tissue browning and exerts thermogenic actions in vivo
title_full Treatment with atrial natriuretic peptide induces adipose tissue browning and exerts thermogenic actions in vivo
title_fullStr Treatment with atrial natriuretic peptide induces adipose tissue browning and exerts thermogenic actions in vivo
title_full_unstemmed Treatment with atrial natriuretic peptide induces adipose tissue browning and exerts thermogenic actions in vivo
title_short Treatment with atrial natriuretic peptide induces adipose tissue browning and exerts thermogenic actions in vivo
title_sort treatment with atrial natriuretic peptide induces adipose tissue browning and exerts thermogenic actions in vivo
url https://doi.org/10.1038/s41598-021-96970-9
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