A role for the melatonin-related receptor GPR50 in leptin signaling, adaptive thermogenesis, and torpor

Curr Biol. 2012 Jan 10;22(1):70-7. doi: 10.1016/j.cub.2011.11.043. Epub 2011 Dec 22.


The ability of mammals to maintain a constant body temperature has proven to be a profound evolutionary advantage, allowing members of this class to thrive in most environments on earth. Intriguingly, some mammals employ bouts of deep hypothermia (torpor) to cope with reduced food supply and harsh climates [1, 2]. During torpor, physiological processes such as respiration, cardiac function, and metabolic rate are severely depressed, yet the neural mechanisms that regulate torpor remain unclear [3]. Hypothalamic responses to energy signals, such as leptin, influence the expression of torpor [4-7]. We show that the orphan receptor GPR50 plays an important role in adaptive thermogenesis and torpor. Unlike wild-type mice, Gpr50(-/-) mice readily enter torpor in response to fasting and 2-deoxyglucose administration. Decreased thermogenesis in Gpr50(-/-) mice is not due to a deficit in brown adipose tissue, the principal site of nonshivering thermogenesis in mice [8]. GPR50 is highly expressed in the hypothalamus of several species, including man [9, 10]. In line with this, altered thermoregulation in Gpr50(-/-) mice is associated with attenuated responses to leptin and a suppression of thyrotropin-releasing hormone. Thus, our findings identify hypothalamic circuits involved in torpor and reveal GPR50 to be a novel component of adaptive thermogenesis in mammals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Temperature Regulation / physiology*
  • Fasting
  • Hypothalamus / metabolism
  • Leptin / physiology*
  • Male
  • Mice
  • Mice, Knockout
  • Nerve Tissue Proteins / physiology*
  • Receptors, G-Protein-Coupled / physiology*
  • Signal Transduction
  • Thermogenesis
  • Thyrotropin-Releasing Hormone / metabolism


  • Gpr50 receptor, mouse
  • Leptin
  • Nerve Tissue Proteins
  • Receptors, G-Protein-Coupled
  • Thyrotropin-Releasing Hormone