Molecular clarification of trans-differentiation to brown adipocytes through the action of soluble receptor LR11

• Project/Area Number: 24390231
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Toho University (2013-2014); Chiba University (2012)
• Principal Investigator: BUJO Hideaki 東邦大学, 医学部, 教授 (80291300)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥14,820,000 (Direct Cost: ¥11,400,000、Indirect Cost: ¥3,420,000); Fiscal Year 2014: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2013: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2012: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
• Keywords: LR11 / 脂肪細胞 / 褐色 / エネルギー産生 / トランスディファレンシエーション / 糖尿病 / 可溶性 / 白血病 / アルツハイマー病 / 褐色細胞 / 分化 / 肥満

Outline of Final Research Achievements

The aim of study is to clarify the physiological significance of and molecular mechanism underlying the trans-differentiation of brown from white adipocytes in LR11-deficent mice, together with the analyses of LR11-overexpressing hematological cells and LR11-decreasing neuronal tissues. Our findings demonstrate that the soluble form of LR11 (sLR11) suppresses thermogenesis in adipose tissue in a cell autonomous manner. Mice lacking LR11 were protected from diet-induced obesity due to increased browning of white adipose tissue and hyper-metabolism. In addition, the shedding of LR11 is regulated by proteinase with other molecules, and the soluble form and the left intracellular form may function as independent molecules for the regulation of cell phenotype. Thus, the regulation of slR11 production is expected as a novel target for developing strategies to treat obesity and diabetes.

Research Products

• [Journal Article] Circulating soluble LR11, a novel marker of smooth muscle cell proliferation, is enhanced after coronary stenting in response to vascular injury. (2014)
  • Author(s): Ogita M, Miyauchi K, Jiang M, Kasai T, Tsuboi S, Naito R, Konishi H, Dohi T, Yokoyama T, Okazaki S, Shimada K, Bujo H, Daida H.
  • Journal Title: Atherosclerosis Volume: 237 Pages: 374-378
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] G-CSF induces the release of the soluble form of LR11, a regulator of myeloid cell mobilization in bone marrow (2014)
  • Author(s): Shimizu N, Nakaseko C, Jiang M, Nishii K, Yokote K, Iseki T, Higashi M, Tamaru J, Schneider WJ, Bujo H
  • Journal Title: Ann Hematol Volume: (印刷中) Issue: 7 Pages: 1111-1122
  • DOI: 10.1007/s00277-014-2033-0
  • Peer Reviewed / Open Access
• [Journal Article] The soluble form of LR11 is a regulator of hypoxia-induced, uPAR-mediated adhesion of immature hematological cells (2013)
  • Author(s): Keigo Nishii, Chiaki Nakaseko, Meizi Jiang, Naomi Shimizu, Masahiro Takeuchi, Wolfgang Johann Schneider, and Hideaki Bujo
  • Journal Title: The Journal of Biological Chemistry Volume: 288(17) Issue: 17 Pages: 11877-11886
  • DOI: 10.1074/jbc.m112.442491
  • Peer Reviewed
• [Journal Article] LR11 : a novel biomarker identified in follicular lymphoma (2013)
  • Author(s): Kawaguchi T, Ohwada C, Takeuchi M, Shimizu N, Sakaida E, Takeda Y, Sakai S, Tsukamoto S, Yamazaki A, Sugita Y, Jiang M, Higashi M, Yokote K, Tamura J, Bujo H, Nakaseko C
  • Journal Title: Br J Haematol Volume: 163(2) Issue: 2 Pages: 277-280
  • DOI: 10.1111/bjh.12467
  • Peer Reviewed
• [Journal Article] Platelet-rich plasma inhibits the apoptosis of highly adipogenic homogeneous preadipocytes in an in vitro culture system. (2012)
  • Author(s): Fukaya Y, Kuroda M, Aoyagi Y, Asada S, Kubota Y, Okamoto Y, Nakayama T, Sai to Y, Satoh Y, Bujo H
  • Journal Title: Exp Mol Med Volume: 44 Issue: 5 Pages: 330-339
  • DOI: 10.3858/emm.2012.44.5.037
  • Peer Reviewed
• [Journal Article] Circulating Soluble LRU in Patients with Diabetic Retinopathy. (2012)
  • Author(s): Takahashi M, Bujo H, Shiba T, Jiang M, Maeno T, Shirai K
  • Journal Title: Am J Ophthalmol Volume: 154 Issue: 1 Pages: 187-192
  • DOI: 10.1016/j.ajo.2012.01.035
  • Peer Reviewed