Spexin Regulates Hypothalamic Leptin Action on Feeding Behavior

Bora Jeong, Kwang Kon Kim, Tae Hwan Lee, Han Rae Kim, Byong Seo Park, Jeong Woo Park, Jin Kwon Jeong, Jae Young Seong, Byung Ju Lee

Research output: Contribution to journalArticlepeer-review

Abstract

Spexin (SPX) is a recently identified neuropeptide that is believed to play an important role in the regulation of energy homeostasis. Here, we describe a mediating function of SPX in hy-pothalamic leptin action. Intracerebroventricular (icv) SPX administration induced a decrease in food intake and body weight gain. SPX was found to be expressed in cells expressing leptin receptor ObRb in the mouse hypothalamus. In line with this finding, icv leptin injection increased SPX mRNA in the ObRb‐positive cells of the hypothalamus, which was blocked by treatment with a STAT3 inhibitor. Leptin also increased STAT3 binding to the SPX promoter, as measured by chro-matin immunoprecipitation assays. In vivo blockade of hypothalamic SPX biosynthesis with an an-tisense oligodeoxynucleotide (AS ODN) resulted in a diminished leptin effect on food intake and body weight. AS ODN reversed leptin’s effect on the proopiomelanocortin (POMC) mRNA expression and, moreover, decreased leptin‐induced STAT3 binding to the POMC promoter sequence. These results suggest that SPX is involved in leptin’s action on POMC gene expression in the hypothalamus and impacts the anorexigenic effects of leptin.

Original languageEnglish
Article number236
JournalBiomolecules
Volume12
Issue number2
DOIs
Publication statusPublished - 2022 Feb

Keywords

  • Appetite regulation
  • Energy homeostasis
  • Hypothalamus
  • Spexin

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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