Pu-erh tea extract ameliorates high-fat diet-induced nonalcoholic steatohepatitis and insulin resistance by modulating hepatic IL-6/STAT3 signaling in mice

J Gastroenterol. 2016 Aug;51(8):819-29. doi: 10.1007/s00535-015-1154-0. Epub 2016 Jan 21.


Background: Pu-erh tea, made from the leaves of Camellia sinensis, possesses activities beneficial for human health, including anti-inflammatory, anti-oxidant, and anti-obesity properties.

Objective: We investigated the effects of a pu-erh tea extract (PTE) on nonalcoholic steatohepatitis (NASH) and the molecular mechanisms underlying such effects.

Methods: Eight-week-old male C57BL/6J mice were fed a normal chow diet or high-fat diet (HFD) for 17 weeks, during which PTE was simultaneously administered in drinking water. Body weight, hepatic inflammation, steatosis, insulin sensitivity, expression of lipogenesis- and gluconeogenesis-associated genes, and signal transducer and activator of transcription (STAT)-3 phosphorylation were examined. The anti-steatotic effects of PTE and/or interleukin (IL)-6 were evaluated in HepG2 cells. The lipid accumulation, STAT3 phosphorylation, and expression of lipid metabolism-related genes were analyzed.

Results: PTE inhibited HFD-induced obesity and significantly attenuated HFD-induced hepatic steatosis and liver inflammation, and prevented against liver injury. PTE treatment improved glucose tolerance and insulin sensitivity in HFD-fed mice. Moreover, PTE treatment maintained the intact insulin signal and significantly decreased expression of gluconeogenesis-related genes in the livers of HFD-fed mice. PTE treatment strikingly enhanced STAT3 phosphorylation in the livers of HFD-fed mice. Consistent with this increase in STAT3 phosphorylation, pre-treatment of HepG2 cells with PTE enhanced IL-6-induced STAT3 phosphorylation and attenuated oleic acid-induced steatosis in a STAT3-dependent manner. In contrast, PTE inhibited IL-6-induced STAT3 phosphorylation in macrophages.

Conclusions: PTE ameliorates hepatic lipid metabolism, inflammation, and insulin resistance in mice with HFD-induced NASH, presumably by modulating hepatic IL-6/STAT3 signaling.

Keywords: Insulin resistance; NASH; PTE; STAT3.

MeSH terms

  • Animals
  • Camellia sinensis
  • Cells, Cultured
  • Diet, High-Fat / adverse effects
  • Feces / chemistry
  • Glucose Tolerance Test
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism
  • Insulin Resistance / physiology*
  • Interleukin-6 / metabolism*
  • Lipid Metabolism / drug effects
  • Lipid Metabolism / physiology
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Mice, Inbred C57BL
  • Non-alcoholic Fatty Liver Disease / etiology
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Non-alcoholic Fatty Liver Disease / physiopathology
  • Non-alcoholic Fatty Liver Disease / prevention & control*
  • Phytotherapy / methods*
  • Plant Extracts / pharmacology
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Tea*
  • Weight Gain / drug effects


  • Interleukin-6
  • Plant Extracts
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Tea
  • interleukin-6, mouse