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Effect of Adrenergic Agonists on High-Fat Diet-Induced Hepatic Steatosis in Mice

The autonomic nervous system, consisting of sympathetic and parasympathetic branches, plays an important role in regulating metabolic homeostasis. The sympathetic nervous system (SNS) regulates hepatic lipid metabolism by regulating adrenergic receptor activation, resulting in the stimulation of hep...

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Autores principales: Nakade, Yukiomi, Kitano, Rena, Yamauchi, Taeko, Kimoto, Satoshi, Sakamoto, Kazumasa, Inoue, Tadahisa, Kobayashi, Yuji, Ohashi, Tomohiko, Sumida, Yoshio, Ito, Kiyoaki, Yoneda, Masashi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764675/
https://www.ncbi.nlm.nih.gov/pubmed/33321735
http://dx.doi.org/10.3390/ijms21249392
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author Nakade, Yukiomi
Kitano, Rena
Yamauchi, Taeko
Kimoto, Satoshi
Sakamoto, Kazumasa
Inoue, Tadahisa
Kobayashi, Yuji
Ohashi, Tomohiko
Sumida, Yoshio
Ito, Kiyoaki
Yoneda, Masashi
author_facet Nakade, Yukiomi
Kitano, Rena
Yamauchi, Taeko
Kimoto, Satoshi
Sakamoto, Kazumasa
Inoue, Tadahisa
Kobayashi, Yuji
Ohashi, Tomohiko
Sumida, Yoshio
Ito, Kiyoaki
Yoneda, Masashi
author_sort Nakade, Yukiomi
collection PubMed
description The autonomic nervous system, consisting of sympathetic and parasympathetic branches, plays an important role in regulating metabolic homeostasis. The sympathetic nervous system (SNS) regulates hepatic lipid metabolism by regulating adrenergic receptor activation, resulting in the stimulation of hepatic very-low-density lipoprotein-triglyceride (TG) production in vivo. However, only a few studies on the relationship between SNS and hepatic steatosis have been reported. Here, we investigate the effect of adrenergic receptor agonists on hepatic steatosis in mice fed a high-fat diet (HFD). The α-adrenergic receptor agonist phenylephrine (10 mg/kg/d) or the β-adrenergic receptor agonist isoproterenol (30 mg/kg/d) was coadministered with HFD to male mice. After five weeks, hepatic steatosis, TG levels, and hepatic fat metabolism-related biomarkers were examined. HFD treatment induced hepatic steatosis, and cotreatment with phenylephrine, but not isoproterenol, attenuated this effect. Phenylephrine administration upregulated the mRNA levels of hepatic peroxisome proliferator-activated receptor alpha and its target genes (such as carnitine palmitoyltransferase 1) and increased hepatic β-hydroxybutyrate levels. Additionally, phenylephrine treatment increased the expression of the autophagosomal marker LC3-II but decreased that of p62, which is selectively degraded during autophagy. These results indicate that phenylephrine inhibits hepatic steatosis through stimulation of β-oxidation and autophagy in the liver.
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spelling pubmed-77646752020-12-27 Effect of Adrenergic Agonists on High-Fat Diet-Induced Hepatic Steatosis in Mice Nakade, Yukiomi Kitano, Rena Yamauchi, Taeko Kimoto, Satoshi Sakamoto, Kazumasa Inoue, Tadahisa Kobayashi, Yuji Ohashi, Tomohiko Sumida, Yoshio Ito, Kiyoaki Yoneda, Masashi Int J Mol Sci Article The autonomic nervous system, consisting of sympathetic and parasympathetic branches, plays an important role in regulating metabolic homeostasis. The sympathetic nervous system (SNS) regulates hepatic lipid metabolism by regulating adrenergic receptor activation, resulting in the stimulation of hepatic very-low-density lipoprotein-triglyceride (TG) production in vivo. However, only a few studies on the relationship between SNS and hepatic steatosis have been reported. Here, we investigate the effect of adrenergic receptor agonists on hepatic steatosis in mice fed a high-fat diet (HFD). The α-adrenergic receptor agonist phenylephrine (10 mg/kg/d) or the β-adrenergic receptor agonist isoproterenol (30 mg/kg/d) was coadministered with HFD to male mice. After five weeks, hepatic steatosis, TG levels, and hepatic fat metabolism-related biomarkers were examined. HFD treatment induced hepatic steatosis, and cotreatment with phenylephrine, but not isoproterenol, attenuated this effect. Phenylephrine administration upregulated the mRNA levels of hepatic peroxisome proliferator-activated receptor alpha and its target genes (such as carnitine palmitoyltransferase 1) and increased hepatic β-hydroxybutyrate levels. Additionally, phenylephrine treatment increased the expression of the autophagosomal marker LC3-II but decreased that of p62, which is selectively degraded during autophagy. These results indicate that phenylephrine inhibits hepatic steatosis through stimulation of β-oxidation and autophagy in the liver. MDPI 2020-12-10 /pmc/articles/PMC7764675/ /pubmed/33321735 http://dx.doi.org/10.3390/ijms21249392 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nakade, Yukiomi
Kitano, Rena
Yamauchi, Taeko
Kimoto, Satoshi
Sakamoto, Kazumasa
Inoue, Tadahisa
Kobayashi, Yuji
Ohashi, Tomohiko
Sumida, Yoshio
Ito, Kiyoaki
Yoneda, Masashi
Effect of Adrenergic Agonists on High-Fat Diet-Induced Hepatic Steatosis in Mice
title Effect of Adrenergic Agonists on High-Fat Diet-Induced Hepatic Steatosis in Mice
title_full Effect of Adrenergic Agonists on High-Fat Diet-Induced Hepatic Steatosis in Mice
title_fullStr Effect of Adrenergic Agonists on High-Fat Diet-Induced Hepatic Steatosis in Mice
title_full_unstemmed Effect of Adrenergic Agonists on High-Fat Diet-Induced Hepatic Steatosis in Mice
title_short Effect of Adrenergic Agonists on High-Fat Diet-Induced Hepatic Steatosis in Mice
title_sort effect of adrenergic agonists on high-fat diet-induced hepatic steatosis in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764675/
https://www.ncbi.nlm.nih.gov/pubmed/33321735
http://dx.doi.org/10.3390/ijms21249392
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