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Two-Week Isocaloric Time-Restricted Feeding Decreases Liver Inflammation without Significant Weight Loss in Obese Mice with Non-Alcoholic Fatty Liver Disease

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

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Aichi Medical University, Nagakute 480-1195, Aichi, Japan
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(24), 9392;
Received: 24 September 2020 / Revised: 7 December 2020 / Accepted: 7 December 2020 / Published: 10 December 2020
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. View Full-Text
Keywords: phenylephrine; isoproterenol; steatosis; β-oxidation; autophagy phenylephrine; isoproterenol; steatosis; β-oxidation; autophagy
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MDPI and ACS Style

Nakade, Y.; Kitano, R.; Yamauchi, T.; Kimoto, S.; Sakamoto, K.; Inoue, T.; Kobayashi, Y.; Ohashi, T.; Sumida, Y.; Ito, K.; Yoneda, M. Effect of Adrenergic Agonists on High-Fat Diet-Induced Hepatic Steatosis in Mice. Int. J. Mol. Sci. 2020, 21, 9392.

AMA Style

Nakade Y, Kitano R, Yamauchi T, Kimoto S, Sakamoto K, Inoue T, Kobayashi Y, Ohashi T, Sumida Y, Ito K, Yoneda M. Effect of Adrenergic Agonists on High-Fat Diet-Induced Hepatic Steatosis in Mice. International Journal of Molecular Sciences. 2020; 21(24):9392.

Chicago/Turabian Style

Nakade, Yukiomi, Rena Kitano, Taeko Yamauchi, Satoshi Kimoto, Kazumasa Sakamoto, Tadahisa Inoue, Yuji Kobayashi, Tomohiko Ohashi, Yoshio Sumida, Kiyoaki Ito, and Masashi Yoneda. 2020. "Effect of Adrenergic Agonists on High-Fat Diet-Induced Hepatic Steatosis in Mice" International Journal of Molecular Sciences 21, no. 24: 9392.

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