Peripheral Spexin Inhibited Food Intake in Mice

Area of Science:

• Neuroendocrinology
• Appetite Regulation
• Neuropeptides

Background:

• Spexin (SPX) is a novel endogenous neuropeptide found in the central nervous system and peripheral tissues.
• The role of spexin in mammalian appetite regulation remains largely unknown.
• Understanding spexin's function is crucial for metabolic research.

Purpose of the Study:

• To investigate the mechanism and effect of peripheral spexin on food intake in mice.
• To determine the receptor subtype involved in spexin's anorectic action.
• To elucidate the hypothalamic pathways modulated by spexin.

Main Methods:

• Intraperitoneal injection of spexin in fasted and freely feeding mice during light and dark periods.
• Administration of GALR2 and GALR3 antagonists to assess receptor involvement.
• Quantitative analysis of hypothalamic neuropeptide mRNA levels (Npy, Agrp, Pomc, Cart, Crh, Orexin, Mch).
• Immunohistochemical staining for c-Fos positive neurons in hypothalamic nuclei.
• Western blot analysis of phosphorylated CaMK2 (p-CaMK2) protein expression.

Main Results:

• Peripheral spexin administration significantly inhibited cumulative food intake in mice.
• The GALR3 antagonist SNAP37889, but not the GALR2 antagonist, antagonized spexin's anorectic effect.
• Spexin reduced hypothalamic Npy mRNA levels.
• Spexin increased c-Fos positive neurons in the hypothalamic anterior hypothalamic area (AHA) and suprachiasmatic nucleus (SCN).
• Spexin upregulated hypothalamic p-CaMK2 protein expression.

Conclusions:

• Acute peripheral spexin injection exerts an anorectic effect in mice.
• The anorectic effect of spexin is likely mediated by the GALR3 receptor.
• Spexin may inhibit food intake by modulating neuropeptide Y (NPY) signaling via p-CaMK2 and c-Fos in the hypothalamus.