Role of Central Leptin Signaling in Renal Macrophage Infiltration

Endocrine Journal

Masato KASAHARA⁴  Takayoshi SUGANAMI¹  Yoshihiro OGAWA¹  Satoshi SUGITA¹  Seiichiro AOE³  Yuri SHIMODA¹  Miyako TANAKA¹  Motohiro TAKEYA⁵  Yasutomi KAMEI¹  Shu TAKEDA² 

[1] Department of Molecular Medicine and Metabolism, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan;Department of Orthopedic Surgery, Tokyo Medical and Dental University, Tokyo, Japan;Department of Home Economics, Otsuma Women’s University, Tokyo, Japan;Foundation for Biomedical Research and Innovation, Kobe, Japan;Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

关键词: Chemotaxis;    Inflammation;    Leptin;    Macrophages;    Melanocortin;   

DOI  :  10.1507/endocrj.K09E-296

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

References(38)Cited-By(7)Monocytes/macrophages are key mediators of wound repair, tissue remodeling, and inflammation. However, the molecular mechanisms underlying macrophage recruitment to the site of inflammation is not fully understood. Leptin acts directly on the hypothalamus, thereby regulating food intake and energy expenditure. The leptin receptor, a single transmembrane protein that belongs to the gp130 family of cytokine receptor superfamily, is expressed not only in the hypothalamus but in a variety of peripheral tissues, suggesting the role of leptin as a pro-inflammatory adipocytokine in peripheral tissues. Here, we show that deficiency of leptin signaling reduces renal macrophage infiltration after unilateral ureteral obstruction (UUO). Bone marrow transplantation studies using leptin signaling-deficient db/db mice revealed that leptin signaling in bone marrow cells may not play a major role in the UUO-induced renal macrophage infiltration. Interestingly, central leptin administration reverses the otherwise reduced UUO-induced renal macrophage infiltration in leptindeficient ob/ob mice. This is effectively abolished by central co-administration of SHU9119, a melanocortin-3 receptor/melanocortin-4 receptor antagonist. This study demonstrates that central leptin administration in ob/ ob mice accelerates renal macrophage infiltration through the melanocortin system, thereby suggesting that the central nervous system, which is inherent to integrate information from throughout the organism, is able to control peripheral inflammation.

【 授权许可】

Unknown