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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MDPI AG
2020-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/24/9392 |
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| author | Yukiomi Nakade Rena Kitano Taeko Yamauchi Satoshi Kimoto Kazumasa Sakamoto Tadahisa Inoue Yuji Kobayashi Tomohiko Ohashi Yoshio Sumida Kiyoaki Ito Masashi Yoneda |
| author_facet | Yukiomi Nakade Rena Kitano Taeko Yamauchi Satoshi Kimoto Kazumasa Sakamoto Tadahisa Inoue Yuji Kobayashi Tomohiko Ohashi Yoshio Sumida Kiyoaki Ito Masashi Yoneda |
| author_sort | Yukiomi Nakade |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T14:12:14Z |
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| id | doaj.art-f1280dbc32904e9f83dc4437b953e9cd |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T14:12:14Z |
| publishDate | 2020-12-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-f1280dbc32904e9f83dc4437b953e9cd2023-11-21T00:07:57ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-12-012124939210.3390/ijms21249392Effect of Adrenergic Agonists on High-Fat Diet-Induced Hepatic Steatosis in MiceYukiomi Nakade0Rena Kitano1Taeko Yamauchi2Satoshi Kimoto3Kazumasa Sakamoto4Tadahisa Inoue5Yuji Kobayashi6Tomohiko Ohashi7Yoshio Sumida8Kiyoaki Ito9Masashi Yoneda10Division of Gastroenterology and Hepatology, Department of Internal Medicine, Aichi Medical University, Nagakute 480-1195, Aichi, JapanDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Aichi Medical University, Nagakute 480-1195, Aichi, JapanDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Aichi Medical University, Nagakute 480-1195, Aichi, JapanDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Aichi Medical University, Nagakute 480-1195, Aichi, JapanDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Aichi Medical University, Nagakute 480-1195, Aichi, JapanDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Aichi Medical University, Nagakute 480-1195, Aichi, JapanDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Aichi Medical University, Nagakute 480-1195, Aichi, JapanDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Aichi Medical University, Nagakute 480-1195, Aichi, JapanDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Aichi Medical University, Nagakute 480-1195, Aichi, JapanDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Aichi Medical University, Nagakute 480-1195, Aichi, JapanDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Aichi Medical University, Nagakute 480-1195, Aichi, JapanThe 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.https://www.mdpi.com/1422-0067/21/24/9392phenylephrineisoproterenolsteatosisβ-oxidationautophagy |
| spellingShingle | Yukiomi Nakade Rena Kitano Taeko Yamauchi Satoshi Kimoto Kazumasa Sakamoto Tadahisa Inoue Yuji Kobayashi Tomohiko Ohashi Yoshio Sumida Kiyoaki Ito Masashi Yoneda Effect of Adrenergic Agonists on High-Fat Diet-Induced Hepatic Steatosis in Mice International Journal of Molecular Sciences phenylephrine isoproterenol steatosis β-oxidation autophagy |
| 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 | phenylephrine isoproterenol steatosis β-oxidation autophagy |
| url | https://www.mdpi.com/1422-0067/21/24/9392 |
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