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Spexin Regulates Hypothalamic Leptin Action on Feeding Behavior.

Bora Jeong1, Kwang-Kon Kim1, Tae-Hwan Lee1

  • 1Department of Biological Sciences, College of Natural Sciences, University of Ulsan, Ulsan 44610, Korea.

Biomolecules
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Spexin (SPX) is a neuropeptide regulating energy balance. This study shows SPX mediates leptin

Keywords:
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Area of Science:

  • Neuroendocrinology
  • Metabolism Research
  • Molecular Biology

Background:

  • Energy homeostasis is crucial for survival, involving complex hormonal signaling pathways.
  • Leptin is a key hormone regulating appetite and body weight, acting through hypothalamic receptors.
  • The neuropeptide Spexin (SPX) has emerged as a potential regulator of energy balance.

Purpose of the Study:

  • To investigate the role of Spexin (SPX) in mediating the effects of leptin on energy homeostasis.
  • To elucidate the molecular mechanisms by which SPX interacts with leptin signaling in the hypothalamus.

Main Methods:

  • Intracerebroventricular (icv) administration of SPX and leptin in mice.
  • Analysis of SPX and proopiomelanocortin (POMC) mRNA expression.
  • Chromatin immunoprecipitation (ChIP) assays to assess STAT3 binding to promoter regions.
  • In vivo blockade of SPX biosynthesis using antisense oligodeoxynucleotides (AS ODN).

Main Results:

  • icv SPX administration reduced food intake and body weight gain.
  • Leptin increased SPX mRNA expression in hypothalamic cells expressing the leptin receptor (ObRb).
  • Leptin-induced STAT3 activation and binding to SPX and POMC promoters were observed.
  • Blockade of SPX biosynthesis attenuated leptin's anorexigenic effects and its impact on POMC gene expression.

Conclusions:

  • Spexin (SPX) plays a critical role in mediating leptin's action within the hypothalamus.
  • SPX is involved in the regulation of POMC gene expression and the anorexigenic effects of leptin.
  • These findings highlight SPX as a potential therapeutic target for metabolic disorders.