Treatment With Atrial Natriuretic Peptide Induces Adipose Tissue Browning and Exerts Thermogenic Actions in Vivo.

Abstract

Background: Although natriuretic peptides (NPs) classically act on the renal and cardiovascular systems, increasing evidence suggests that NPs also largely coordinate inter-organ metabolic crosstalk with adipose tissues and play a critical role in energy metabolism. We recently reported that A-type NP (ANP) raises the intracellular temperature in cultured adipocytes in a low-temperature-sensitive manner. We herein investigated whether or not exogenous ANP treatment exerts a significant impact on adipose tissues in vivo using diet-induced obese mice.Methods and Results: C57BL/6 mice fed a high-fat diet (HFD) or normal-fat diet (NFD) for 13 weeks were treated with or without ANP infusion subcutaneously via osmotic pump for another 3 weeks (0.5 μg/kg/min). The intraperitoneal glucose tolerance test and insulin tolerance test showed that ANP treatment significantly ameliorated HFD-induced insulin resistance. Histological analyses revealed that HFD increased the 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 (eWAT), and hepatic steatosis, all of which were substantially attenuated by ANP treatment. Likewise, ANP treatment markedly increased the expression of uncoupling protein-1 (UCP1), a specific marker of BAT, in iWAT (browning). ANP also further increased the UCP1 expression in BAT with an NFD. Accordingly, the cold tolerance test (at 4 °C for 4 h) demonstrated that the ANP-treated mice were tolerant to cold exposure.Conclusions: Exogenous ANP administration ameliorates HFD-induced insulin resistance by attenuating hepatic steatosis as well as by inducing adipose tissue browning (activation of the adipose tissue thermogenic program), leading to in vivo thermogenesis during cold exposure.

Serum neuregulin 4 is negatively correlated with insulin sensitivity in humans and impairs mitochondrial respiration in HepG2 cells

“…The benefitial impact of NRG4 on metabolism observed in mice might be explained by the direct effects of NRG4 on adipose tissue, increasing sympathetic innervations, and the enhancement of BAT activity and browning of WAT (Rosell et al, 2014;Comas et al, 2019), but not on liver metabolism. In fact, while in mice the activation of BAT and the promotion of WAT browning ameliorate insulin sensitivity, liver steatosis and glucose tolerance in obesogenic conditions (Wang et al, 2015;Kimura et al, 2021), the impact of WAT browning on obesity or insulin resistance in humans is less relevant (Barquissau et al, 2018;Comas et al, 2019).…”

Carboxymethyl Chitosan/Sodium Alginate/Chitosan Quaternary Ammonium Salt Composite Hydrogel Supported 3J for the Treatment of Oral Ulcer

“…The samples were treated for histopathology analysis as described previously [48]. The skin tissue at ulcer was excised and fixed with 4.0% formalin.…”