Spexin Regulates Hypothalamic Leptin Action on Feeding Behavior.

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

doi:10.3390/biom12020236

Bora Jeong, Tae-Hwan Lee + Show 7 more

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https://doi.org/10.3390/biom12020236

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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 hypothalamic 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 chromatin immunoprecipitation assays. In vivo blockade of hypothalamic SPX biosynthesis with an antisense 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.

Highlights

Spexin (SPX), known as neuropeptide Q, has recently been identified by bioinformatics techniques [1,2]
Because SPX induced a decrease in food intake, we investigated the SPX-induced change in POMC and agouti-related peptide (AgRP)
POMC mRNA expression was significantly increased in the mouse mediobasal hypothalamus (MBH)

Summary

Introduction

Spexin (SPX), known as neuropeptide Q, has recently been identified by bioinformatics techniques [1,2]. SPX is a secreted 14-amino-acid peptide that is highly conserved from fish to mammals [3,4,5]. It is widely expressed in the central nervous system and peripheral tissues such as the liver, gonad and kidney in rodents, fish and humans [1,2,3,4,5,6,7]. Intraperitoneal injection of SPX induced anorexia, accompanied by an increase in hypothalamic expression of anorexigenic neuropeptide proopiomelanocortin (POMC), with a simultaneous decrease in orexigenic neuropeptide Y (NPY) and agouti-related peptide (AgRP) [4]. A recent study reported that intracerebroventricular (icv) injection of SPX increased hypothalamic mRNA

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