Met-enkephalin improves metabolic syndrome in high fat diet challenged mice through promotion of adipose tissue browning

Toxicol Appl Pharmacol. 2018 Nov 15:359:12-23. doi: 10.1016/j.taap.2018.09.015. Epub 2018 Sep 14.


Obesity and its related metabolic disorders including insulin resistance and fatty liver become major public health concerns in both developed and developing countries. Brown adipose tissue (BAT), a critical organ of energy expenditure due to thermogenesis, has been considered as an attractive target for prevention or treatment of obesity and obesity related diseases. Previous studies indicate Met-enkephalin (MetEnk) has the potential on adipocyte browning, however, whether MetEnk displays the impact on adipocyte browning in vivo to improve obesity associated morbidities is still unclear. In the present study, we showed that MetEnk effectively prevented high fat diet (HFD) induced C57BL/6J mice weight gain, clearly enhanced glucose tolerance and insulin sensitivity, and dramatically reduced hepatic steatosis in HFD fed mice. Mechanically, MetEnk restored protein kinase A (PKA) signaling pathway in HFD challenged mice and promoted subcutaneous white adipose tissue (WAT) browning. Our study suggests that MetEnk can be considered as a potential therapeutic peptide for diet-induced obesity and metabolic disorders.

Keywords: Fat browning; Hepatic steatosis; High fat diet; Insulin resistance; Met-enkephalin; Uncoupling protein 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes, Brown / drug effects
  • Adipose Tissue, Brown / drug effects*
  • Adipose Tissue, Brown / growth & development
  • Adipose Tissue, Brown / pathology
  • Animals
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Cytokines / metabolism
  • Diet, High-Fat / adverse effects*
  • Enkephalin, Methionine / therapeutic use*
  • Glucose Intolerance / drug therapy
  • Insulin Resistance
  • Male
  • Metabolic Syndrome / drug therapy*
  • Metabolic Syndrome / pathology
  • Mice
  • Mice, Inbred C57BL
  • Non-alcoholic Fatty Liver Disease / drug therapy
  • Receptors, Opioid, delta / drug effects


  • Cytokines
  • Receptors, Opioid, delta
  • Enkephalin, Methionine
  • Cyclic AMP-Dependent Protein Kinases