Role of central leptin signaling in renal macrophage infiltration

Miyako Tanaka, Takayoshi Suganami, Satoshi Sugita, Yuri Shimoda, Masato Kasahara, Seiichiro Aoe, Motohiro Takeya, Shu Takeda, Yasutomi Kamei, Yoshihiro Ogawa

研究成果: Contribution to journalArticle査読

20 被引用数 (Scopus)

抄録

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 leptin-deficient 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.

本文言語英語
ページ(範囲)61-72
ページ数12
ジャーナルEndocrine Journal
57
1
DOI
出版ステータス出版済み - 2010
外部発表はい

All Science Journal Classification (ASJC) codes

  • 内分泌学、糖尿病および代謝内科学
  • 内分泌学

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