Differential gene regulation of GHSR signaling pathway in the arcuate nucleus and NPY neurons by fasting, diet-induced obesity, and 17β-estradiol

• Published in: Molecular and cellular endocrinology 2016-02, Vol.422, p.42-56
• Main Authors: Yasrebi, Ali, Hsieh, Anna, Mamounis, Kyle J., Krumm, Elizabeth A., Yang, Jennifer A., Magby, Jason, Hu, Pu, Roepke, Troy A.
• Format: Article
• Language: English
• Subjects: 17β-Estradiol; Animals; Arcuate nucleus; Arcuate Nucleus of Hypothalamus - metabolism; Diet-induced obesity; Estradiol - pharmacology; Fasting; Fasting - metabolism; Female; Females; Gene expression; Gene Expression Regulation; Genes; Ghrelin; Male; Males; Mice; Neurons; Neurons - metabolism; Neuropeptide y; Neuropeptide Y - metabolism; Obesity; Obesity - etiology; Obesity - metabolism; Receptors; Receptors, Ghrelin - genetics; Receptors, Ghrelin - metabolism; Sex Factors; Signal Transduction
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/j.mce.2015.11.007

Ghrelin's receptor, growth hormone secretagogue receptor (GHSR), is highly expressed in the arcuate nucleus (ARC) and in neuropeptide Y (NPY) neurons. Fasting, diet-induced obesity (DIO), and 17β-estradiol (E2) influence ARC Ghsr expression. It is unknown if these effects occur in NPY neurons. Therefore, we examined the expression of Npy, Agrp, and GHSR signaling pathway genes after fasting, DIO, and E2 replacement in ARC and pools of NPY neurons. In males, fasting increased ARC Ghsr and NPY Foxo1 but decreased NPY Ucp2. In males, DIO decreased ARC and NPY Ghsr and Cpt1c. In fed females, E2 increased Agrp, Ghsr, Cpt1c, and Foxo1 in ARC. In NPY pools, E2 decreased Foxo1 in fed females but increased Foxo1 in fasted females. DIO in females suppressed Agrp and augmented Cpt1c in NPY neurons. In summary, genes involved in GHSR signaling are differentially regulated between the ARC and NPY neurons in a sex-dependent manner. •Fasting in males had differential effects on expression of Foxo1 and Ucp2 expression.•In males, DIO suppressed ARC and NPY Ghsr and Cpt1c expression.•In females, E2 augmented ARC Ghsr, Cpt1c, and Foxo1 but suppressed NPY Foxo1.•In females, DIO suppressed ARC Agrp and augmented NPY Cpt1c.•Ghrelin suppressed M-current activity by ∼50% in NPY neurons from fed male mice.