Inflammation and adipose tissue macrophages in lipodystrophic mice.

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  • Author(s): Herrero L;Herrero L; Shapiro H; Nayer A; Lee J; Shoelson SE
  • Source:
    Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2010 Jan 05; Vol. 107 (1), pp. 240-5. Date of Electronic Publication: 2009 Dec 10.
  • Publication Type:
    Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE
    • Publication Information:
      Original Publication: Washington, DC : National Academy of Sciences
    • Subject Terms:
      Lipodystrophy*/immunology ; Lipodystrophy*/pathology; Adipose Tissue/*cytology ; Inflammation/*immunology ; Macrophages/*cytology; Adipose Tissue/immunology ; Adipose Tissue/pathology ; Adipose Tissue/transplantation ; Animals ; Apoptosis/physiology ; Disease Models, Animal ; Humans ; Insulin Resistance/physiology ; Macrophages/immunology ; Mice ; Mice, Inbred C57BL ; Mice, Obese ; Mice, Transgenic ; Obesity/immunology ; Obesity/pathology ; Phenotype ; Sterol Regulatory Element Binding Protein 1/genetics ; Sterol Regulatory Element Binding Protein 1/metabolism ; Tissue Transplantation
    • Abstract:
      Lipodystrophy and obesity are opposites in terms of a deficiency versus excess of adipose tissue mass, yet these conditions are accompanied by similar metabolic consequences, including insulin resistance, dyslipidemia, hepatic steatosis, and increased risk for diabetes and atherosclerosis. Hepatic and myocellular steatosis likely contribute to metabolic dysregulation in both states. Inflammation and macrophage infiltration into adipose tissue also appear to participate in the pathogenesis of obesity-induced insulin resistance, but their contributions to lipodystrophy-induced insulin resistance have not been evaluated. We used aP2-nSREBP-1c transgenic (Tg) mice, an established model of lipodystrophy, to ask this question. Circulating cytokine elevations suggested systemic inflammation but even more dramatic was the number of infiltrating macrophages in all white and brown adipose tissue depots of the Tg mice; in contrast, there was no evidence of inflammatory infiltrates or responses in any other tissue including liver. Despite there being overt evidence of adipose tissue inflammation, antiinflammatory strategies including salicylate treatment and genetic suppression of myeloid NF-kappaB signaling that correct insulin resistance in obesity were ineffective in the lipodystrophic mice. We further showed that adipose tissue macrophages (ATMs) in lipodystrophy and obesity are very different in terms of activation state, gene expression patterns, and response to lipopolysaccharide. Although ATMs are even more abundant in lipodystrophy than in obesity, they have distinct phenotypes and likely roles in tissue remodeling, but do not appear to be involved in the pathogenesis of insulin resistance.
    • References:
      Nat Med. 2005 Feb;11(2):183-90. (PMID: 15685173)
      Eur J Clin Invest. 2002 Jun;32 Suppl 3:14-23. (PMID: 12028371)
      J Clin Invest. 2006 Nov;116(11):3015-25. (PMID: 17053832)
      Science. 1994 Aug 12;265(5174):956-9. (PMID: 8052854)
      Science. 2001 Aug 31;293(5535):1673-7. (PMID: 11533494)
      N Engl J Med. 2002 Feb 21;346(8):570-8. (PMID: 11856796)
      Int J Obes (Lond). 2007 Dec;31(12):1763-76. (PMID: 17653062)
      Nature. 2002 Nov 21;420(6913):333-6. (PMID: 12447443)
      J Clin Invest. 2003 Dec;112(12):1796-808. (PMID: 14679176)
      N Engl J Med. 2004 Mar 18;350(12):1220-34. (PMID: 15028826)
      Science. 2004 Oct 15;306(5695):457-61. (PMID: 15486293)
      Nat Med. 2009 Aug;15(8):930-9. (PMID: 19633656)
      J Clin Invest. 2000 Feb;105(3):271-8. (PMID: 10675352)
      Diabetes Care. 2008 Feb;31(2):289-94. (PMID: 17959861)
      J Clin Endocrinol Metab. 2007 Jun;92(6):2272-9. (PMID: 17374708)
      Antivir Ther. 2007;12(4):489-500. (PMID: 17668557)
      J Clin Invest. 2007 Jan;117(1):175-84. (PMID: 17200717)
      Prog Lipid Res. 2006 Jan;45(1):42-72. (PMID: 16445986)
      J Clin Invest. 2006 Jan;116(1):33-5. (PMID: 16395402)
      J Clin Invest. 2003 Dec;112(12):1821-30. (PMID: 14679177)
      Am J Physiol Endocrinol Metab. 2004 Feb;286(2):E261-71. (PMID: 14532165)
      Clin Transl Sci. 2008 May;1(1):36-43. (PMID: 19337387)
      Cell Metab. 2007 Nov;6(5):386-97. (PMID: 17983584)
      Nat Rev Immunol. 2007 Dec;7(12):964-74. (PMID: 18037898)
      Physiol Rev. 2007 Apr;87(2):507-20. (PMID: 17429039)
      Diabetes. 2007 Dec;56(12):2910-8. (PMID: 17848624)
      Nature. 1999 Sep 2;401(6748):73-6. (PMID: 10485707)
      Cell Metab. 2006 Jul;4(1):7-8. (PMID: 16814727)
      Int J Obes Relat Metab Disord. 2004 Dec;28 Suppl 4:S12-21. (PMID: 15592481)
      Gastroenterology. 2007 May;132(6):2169-80. (PMID: 17498510)
      Nat Med. 2005 Feb;11(2):191-8. (PMID: 15685170)
      J Clin Invest. 2002 May;109(10):1321-6. (PMID: 12021247)
      J Clin Invest. 2004 Dec;114(12):1752-61. (PMID: 15599400)
      Genes Dev. 1998 Oct 15;12(20):3182-94. (PMID: 9784493)
    • Grant Information:
      R37 DK51729 United States DK NIDDK NIH HHS; R01 DK45943 United States DK NIDDK NIH HHS; R01 DK73547 United States DK NIDDK NIH HHS; R01 DK045943 United States DK NIDDK NIH HHS; R01 DK073547 United States DK NIDDK NIH HHS; R37 DK051729 United States DK NIDDK NIH HHS; P30 DK36836 United States DK NIDDK NIH HHS; P30 DK036836 United States DK NIDDK NIH HHS
    • Accession Number:
      0 (Srebf1 protein, mouse)
      0 (Sterol Regulatory Element Binding Protein 1)
    • Publication Date:
      Date Created: 20091217 Date Completed: 20100309 Latest Revision: 20211020
    • Publication Date:
      20231215
    • Accession Number:
      PMC2806777
    • Accession Number:
      10.1073/pnas.0905310107
    • Accession Number:
      20007767