title: Generation of leptin receptor bone marrow chimeras: recovery from irradiation, immune cellularity, cytokine expression, and metabolic parameters.
abstract: Leptin regulates appetite and metabolism but also immunity and inflammation. Although functional leptin receptors (LepR) are expressed on hematopoietic cells, the role of these receptors in regulating immune function in vivo remains controversial. To clarify this issue, we performed bone marrow (BM) transplantation between obese db/db mice, lacking LepR, and wild-type (WT) mice. Results indicate that expression of LepR on BM-derived cells directly, though partially, regulates spleen and thymus cellularity, although the environment of db mice contributes to maintaining reduced cellularity of these organs. Selective expression of LepR on BM-derived cells also modulates leptin and adiponectin levels, with induction of a more favorable adipokine environment in the WT→db/db group. However, LepR signaling in BM-derived cells is not involved in regulation of body weight (BW) and composition, glycemia, hepatosteatosis or adipose tissue inflammation, although it modulates expression of interleukin (IL)-1β in the brain. Finally, data indicate that db mice have an increased susceptibility to irradiation compared to WT mice in terms of BW loss and recovery of leukocyte counts in peripheral blood. Therefore, interpretation of results obtained using BM chimeras between WT and db mice should take into account the difference in radiation sensitivity between the two types of animals.
authors.affiliation: Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, Illinois, USA.
authors.forename: Melissa E
authors.initials: ME
authors.lastname: Gove
authors.forename: Christina L
authors.initials: CL
authors.lastname: Sherry
authors.forename: Maria
authors.initials: M
authors.lastname: Pini
authors.forename: Giamila
authors.initials: G
authors.lastname: Fantuzzi
mesh_terms: D052242:Adiponectin / Q000097:blood*; D000818:Animals; D001835:Body Weight / Q000528:radiation effects; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism* / Q000528:radiation effects; D016026:Bone Marrow Transplantation; D001921:Brain / Q000378:metabolism; D046528:Chimerism; D053583:Interleukin-1beta / Q000378:metabolism*; D020738:Leptin / Q000097:blood*; D007958:Leukocyte Count; D007962:Leukocytes / Q000528:radiation effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008820:Mice, Obese; D009765:Obesity / Q000378:metabolism*; D054411:Receptors, Leptin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
chemical_list: D052242:Adiponectin; D053583:Interleukin-1beta; D020738:Leptin; D054411:Receptors, Leptin
references.citation: Nat Clin Pract Rheumatol. 2007 Dec;3(12):716-24
references.pmid: 18037931
references.citation: Cell Mol Immunol. 2007 Feb;4(1):1-13
references.pmid: 17349207
references.citation: Cytokine Growth Factor Rev. 2007 Jun-Aug;18(3-4):313-25
references.pmid: 17507280
references.citation: Bone Marrow Transplant. 2008 May;41(9):797-804
references.pmid: 18195686
references.citation: J Immunol. 1987 May 15;138(10):3224-9
references.pmid: 3553324
references.citation: Am J Physiol Endocrinol Metab. 2004 Dec;287(6):E1107-13
references.pmid: 15304373
references.citation: J Clin Biochem Nutr. 2007 Mar;40(2):123-30
references.pmid: 18188414
references.citation: Endocrinology. 2006 Nov;147(11):5470-9
references.pmid: 16873541
references.citation: Cytokine. 2005 Mar 21;29(6):270-4
references.pmid: 15749027
references.citation: Obesity (Silver Spring). 2007 Jun;15(6):1419-29
references.pmid: 17557979
references.citation: Gastroenterology. 2007 May;132(6):2169-80
references.pmid: 17498510
references.citation: Bone Marrow Transplant. 2000 Feb;25(4):427-33
references.pmid: 10723587
references.citation: J Immunol. 1983 Mar;130(3):1195-9
references.pmid: 6571875
references.citation: Brain Behav Immun. 2009 May;23(4):405-10
references.pmid: 18996468
references.citation: J Clin Invest. 1978 Feb;61(2):243-50
references.pmid: 340468
references.citation: J Immunol. 2006 Sep 1;177(5):2899-907
references.pmid: 16920925
references.citation: J Leukoc Biol. 2000 Oct;68(4):437-46
references.pmid: 11037963
references.citation: Proc Natl Acad Sci U S A. 2000 Feb 29;97(5):2367-72
references.pmid: 10681432
references.citation: Arterioscler Thromb Vasc Biol. 2001 Oct;21(10):1674-80
references.pmid: 11597944
references.citation: Diabetes. 2003 May;52(5):1104-10
references.pmid: 12716739
references.citation: Cancer Epidemiol Biomarkers Prev. 2010 Jan;19(1):170-81
references.pmid: 20056636
references.citation: Endocrinology. 2008 Oct;149(10):5209-18
references.pmid: 18583419
references.citation: J Clin Invest. 2001 Oct;108(8):1113-21
references.pmid: 11602618
references.citation: Cell. 2008 Oct 3;135(1):61-73
references.pmid: 18854155
references.citation: Arterioscler Thromb Vasc Biol. 2004 Jan;24(1):29-33
references.pmid: 14551151
references.citation: J Neurosci Res. 1997 Sep 1;49(5):541-50
references.pmid: 9302075
references.citation: Brain Res Mol Brain Res. 1996 Dec 31;43(1-2):209-18
references.pmid: 9037535
references.citation: Int J Radiat Oncol Biol Phys. 2009 Jul 1;74(3):934-41
references.pmid: 19480972
references.citation: Am J Physiol Endocrinol Metab. 2009 May;296(5):E1003-12
references.pmid: 19116375
references.citation: Atherosclerosis. 2009 Jun;204(2):388-94
references.pmid: 19070857
references.citation: J Clin Invest. 1999 Oct;104(8):1051-9
references.pmid: 10525043
references.citation: Nature. 1998 Aug 27;394(6696):897-901
references.pmid: 9732873
references.citation: Cell Metab. 2005 Mar;1(3):169-78
references.pmid: 16054060