Intermittent restraint-induced sympathetic activation attenuates hepatic steatosis and inflammation in a high-fat diet-fed mouse model

Sung Bae Lee, Hyeong Geug Kim, Jin Seok Lee, Won Yong Kim, Myong Min Lee, Yun Hee Kim, Jung Ok Lee, Hyeon Soo Kim, Chang Gue Son

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


Nonalcoholic fatty liver disease (NAFLD) is very prevalent worldwide and is associated with insulin resistance and metabolic syndrome. Stress is a physiological and biological response to maintain homeostasis of the body against stressors while severe stress response is an important contributor to various illnesses, including metabolic syndrome and brain disorders. We have evaluated the effects of intermittent restraint stress on NAFLD in a high-fat diet (HFD)-fed mouse model. C57/BL6 mice had free access to a 60% HFD for 8 wk, with or without intermittent restraint stress (3 h) conducted three times a week. HFD administration increased fat accumulation in liver tissues. Unlike the stressed standard diet group, the levels of hepatic total cholesterol and triglycerides were significantly ameliorated in the HFD with stress group compared with the HFD alone group. These beneficial results were in accordance with serum levels of liver enzymes (aspartate transaminase, alanine transaminase) and hepatic levels of TNF-α and oxidative stress parameters (reactive oxygen species, nitric oxide, and malondialdehyde). The intermittent restraint stress significantly attenuated the HFD-derived alterations in serum insulin levels, hepatic protein kinase B activity, and gene expression, especially related to lipogenesis. This intermittent restraint stress also elevated the serum epinephrine concentration and activated the adrenergic receptor β2 or β3 in livers or white adipose tissue (WAT). Activation of energy expenditure markers (uncoupling protein 1, peroxisome proliferator-activated receptor-γ coactivator-1α) in brown adipose tissue and the browning of WAT were also observed in the HFD with stress group. Taken together, our findings showed the beneficial effects of sympathetic activation by intermittent restraint stress on HFD-induced hepatic steatosis and partial inflammation.

Original languageEnglish
Pages (from-to)G811-G823
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Issue number6
Publication statusPublished - 2019

Bibliographical note

Funding Information:
This research was supported by grants from the Korea Institute of Oriental Medicine (K16842) and the National Research Foundation of Korea (2018R1A6A1A03025221).

Publisher Copyright:
Copyright © 2019 the American Physiological Society.


  • Beneficial effects
  • NASH
  • Stress
  • Sympathetic activation

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)


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