Angiopoietin-Like Growth Factor Involved in Leptin Signaling in the Hypothalamus

• Main Authors: Yunseon Jang, Jun Young Heo, Min Joung Lee, Jiebo Zhu, Changjun Seo, Da Hyun Go, Sung Kyung Yoon, Date Yukari, Yuichi Oike, Jong-Woo Sohn, Minho Shong, Gi Ryang Kweon
• Format: Article
• Language: English
• Published: MDPI AG 2021-03-01
• Series: International Journal of Molecular Sciences
• Subjects: hypothalamus; AGF; leptin; POMC neuron
• Online Access: https://www.mdpi.com/1422-0067/22/7/3443
• ISSN: 1661-6596; 1422-0067

The hypothalamic regulation of appetite governs whole-body energy balance. Satiety is regulated by endocrine factors including leptin, and impaired leptin signaling is associated with obesity. Despite the anorectic effect of leptin through the regulation of the hypothalamic feeding circuit, a distinct downstream mediator of leptin signaling in neuron remains unclear. Angiopoietin-like growth factor (AGF) is a peripheral activator of energy expenditure and antagonizes obesity. However, the regulation of AGF expression in brain and localization to mediate anorectic signaling is unknown. Here, we demonstrated that AGF is expressed in proopiomelanocortin (POMC)-expressing neurons located in the arcuate nucleus (ARC) of the hypothalamus. Unlike other brain regions, hypothalamic AGF expression is stimulated by leptin-induced signal transducers and activators of transcription 3 (STAT3) phosphorylation. In addition, leptin treatment to hypothalamic N1 cells significantly enhanced the promoter activity of AGF. This induction was abolished by the pretreatment of ruxolitinib, a leptin signaling inhibitor. These results indicate that hypothalamic AGF expression is induced by leptin and colocalized to POMC neurons.