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

H Kimura, T Nagoshi, Y Oi, A Yoshii, Y Tanaka… - Scientific Reports, 2021 - nature.com
H Kimura, T Nagoshi, Y Oi, A Yoshii, Y Tanaka, H Takahashi, Y Kashiwagi, TD Tanaka…
Scientific Reports, 2021nature.com
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 …
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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