Caffeine inhibits hypothalamic A 1 R to excite oxytocin neuron and ameliorate dietary obesity in mice

Nat Commun. 2017 Jun 27;8:15904. doi: 10.1038/ncomms15904.

Abstract

Caffeine, an antagonist of the adenosine receptor A1R, is used as a dietary supplement to reduce body weight, although the underlying mechanism is unclear. Here, we report that adenosine level in the cerebrospinal fluid, and hypothalamic expression of A1R, are increased in the diet-induced obesity (DIO) mouse. We find that mice with overexpression of A1R in the neurons of paraventricular nucleus (PVN) of the hypothalamus are hyperphagic, have glucose intolerance and high body weight. Central or peripheral administration of caffeine reduces the body weight of DIO mice by the suppression of appetite and increasing of energy expenditure. We also show that caffeine excites oxytocin expressing neurons, and blockade of the action of oxytocin significantly attenuates the effect of caffeine on energy balance. These data suggest that caffeine inhibits A1Rs expressed on PVN oxytocin neurons to negatively regulate energy balance in DIO mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caffeine / administration & dosage
  • Caffeine / metabolism*
  • Diet, High-Fat / adverse effects
  • Energy Metabolism
  • Glucose / metabolism
  • Humans
  • Hypothalamus / metabolism*
  • Leptin / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neurons / metabolism
  • Obesity / diet therapy
  • Obesity / etiology
  • Obesity / genetics
  • Obesity / metabolism*
  • Oxytocin / metabolism*
  • Paraventricular Hypothalamic Nucleus / metabolism
  • Purinergic P1 Receptor Antagonists / metabolism
  • Receptors, Purinergic P1 / genetics
  • Receptors, Purinergic P1 / metabolism*

Substances

  • Leptin
  • Purinergic P1 Receptor Antagonists
  • Receptors, Purinergic P1
  • Caffeine
  • Oxytocin
  • Glucose