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

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)61-72
Number of pages12
JournalEndocrine Journal
Volume57
Issue number1
DOIs
Publication statusPublished - 2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Fingerprint Dive into the research topics of 'Role of central leptin signaling in renal macrophage infiltration'. Together they form a unique fingerprint.

Cite this