Novel Insight into the Role of the Kiss1/GPR54 System in Energy Metabolism in Major Metabolic Organs

Cells. 2022 Oct 6;11(19):3148. doi: 10.3390/cells11193148.


The Kiss1/GPR54 system is a multifunctional genetic system with an essential role in regulating energy balance and metabolic homeostasis. In the mammalian hypothalamus, two major populations of neurons, the rostral periventricular region of the third ventricle (RP3V) and the arcuate nucleus (ARC), produced kisspeptin. Kiss1ARC neurons input kisspeptin and glutamate to feeding-associated neurons to regulate energy intake and expenditure balance. Kisspeptin in the peripheral circulation is involved in lipid accumulation in adipose tissue. In the hepatic and pancreatic circuits, kisspeptin signaling affects insulin secretion, suggesting the critical role of the Kiss1/GPR54 system in regulating glucose and lipid metabolism. In addition, this review also predicts the role of the Kiss1/GPRS4 system in skeletal muscle in association with exercise performance. Recent studies have focused on the link between kisspeptin signaling and energy homeostasis, further investigation of potential function is warranted. Therefore, this review summarizes the role of the Kiss1/GPRS4 system in the major metabolic organs in relation to energy metabolism homeostasis, aiming to endow the reader with a critical and updated view of the Kiss1/GPR54 system in energy metabolism.

Keywords: Kiss1/GPR54 system; energy metabolism; kisspeptin.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Energy Metabolism*
  • Glucose
  • Glutamates / metabolism
  • Kisspeptins* / genetics
  • Kisspeptins* / metabolism
  • Lipids
  • Mammals / metabolism


  • Glutamates
  • Kisspeptins
  • Lipids
  • Glucose

Grant support

This work was supported by the National Natural Science Foundation of China (No.32071173) and the Central University’s Special Fund for Basic Scientific Research (No.2022YB013).