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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Nature Portfolio
2021-08-01
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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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language | English |
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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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