IL-27 signalling promotes adipocyte thermogenesis and energy expenditure

Nature. 2021 Dec;600(7888):314-318. doi: 10.1038/s41586-021-04127-5. Epub 2021 Nov 24.


Thermogenesis in brown and beige adipose tissue has important roles in maintaining body temperature and countering the development of metabolic disorders such as obesity and type 2 diabetes1,2. Although much is known about commitment and activation of brown and beige adipose tissue, its multiple and abundant immunological factors have not been well characterized3-6. Here we define a critical role of IL-27-IL-27Rα signalling in improving thermogenesis, protecting against diet-induced obesity and ameliorating insulin resistance. Mechanistic studies demonstrate that IL-27 directly targets adipocytes, activating p38 MAPK-PGC-1α signalling and stimulating the production of UCP1. Notably, therapeutic administration of IL-27 ameliorated metabolic morbidities in well-established mouse models of obesity. Consistently, individuals with obesity show significantly decreased levels of serum IL-27, which can be restored after bariatric surgery. Collectively, these findings show that IL-27 has an important role in orchestrating metabolic programs, and is a highly promising target for anti-obesity immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / metabolism*
  • Animals
  • Bariatric Surgery
  • Disease Models, Animal
  • Energy Metabolism*
  • Female
  • Humans
  • Insulin Resistance
  • Interleukin-27 / blood
  • Interleukin-27 / metabolism*
  • Interleukin-27 / therapeutic use
  • Male
  • Mice
  • Obesity / blood
  • Obesity / drug therapy
  • Obesity / metabolism
  • Obesity / prevention & control
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism
  • Receptors, Interleukin / metabolism
  • Signal Transduction
  • Thermogenesis*
  • Uncoupling Protein 1 / biosynthesis
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Il27ra protein, mouse
  • Interleukin-27
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, mouse
  • Receptors, Interleukin
  • Ucp1 protein, mouse
  • Uncoupling Protein 1
  • p38 Mitogen-Activated Protein Kinases