Adipose Tissue Inflammation and Adrenomedullin Overexpression Contribute to Lipid Dysregulation in Diabetic Pregnancies.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: Oxford University Press Country of Publication: United States NLM ID: 0375362 Publication Model: Print Cited Medium: Internet ISSN: 1945-7197 (Electronic) Linking ISSN: 0021972X NLM ISO Abbreviation: J Clin Endocrinol Metab Subsets: MEDLINE
    • Publication Information:
      Publication: 2017- : New York : Oxford University Press
      Original Publication: Springfield, Ill. : Charles C. Thomas
    • Subject Terms:
      Adipose Tissue/*immunology ; Adrenomedullin/*metabolism ; Diabetes, Gestational/*physiopathology ; Dyslipidemias/*etiology ; Fetal Macrosomia/*etiology ; Inflammation/*complications ; Prenatal Exposure Delayed Effects/*pathology; Adipose Tissue/metabolism ; Adipose Tissue/pathology ; Adrenomedullin/genetics ; Adult ; Diabetes, Gestational/metabolism ; Dyslipidemias/metabolism ; Dyslipidemias/pathology ; Female ; Fetal Macrosomia/metabolism ; Fetal Macrosomia/pathology ; Follow-Up Studies ; Humans ; Lipids/analysis ; Lipolysis ; Omentum/metabolism ; Omentum/pathology ; Pregnancy ; Pregnancy Complications/etiology ; Pregnancy Complications/metabolism ; Pregnancy Complications/pathology ; Prognosis
    • Abstract:
      Context: Impaired maternal lipid metabolism in gestational diabetes mellitus (GDM) has detrimental effects on maternal health and fetal growth. We previously reported the excessive expression of adrenomedullin (ADM) and its receptors in GDM adipose tissues compared with normal glucose-tolerant pregnancies. In the present study, we determined the mechanisms underlying enhanced expression of ADM and its receptors.
      Design: Omental adipose tissue (OAT) samples were collected from women during cesarian section of term pregnancy with nonoverweight (NOW; n = 9), overweight (OW; n = 8), obese (OBS; n = 10), and GDM (n = 10) status.
      Results: The expression of ADM and its receptors was greater in OATs from GDM than from women who were NOW, OW, and OBS. The expression of adipokines, leptin, and resistin were significantly increased, but adiponectin was decreased in OATs from patients with GDM compared with those without GDM. Macrophage infiltration and TNF-α expression were greater in OAT from pregnant women with GDM than in pregnant women without GDM. Furthermore, TNF-α dose dependently increased mRNA for ADM and its receptor components calcitonin receptor-like receptor and receptor activity-modifying proteins 2 and 3 in OAT explants from women who were NOW. Human adipocytes treated with ADM significantly increased glycerol release in culture medium, and the increases of glycerol in culture medium of OAT from women with GDM were attenuated by ADM antagonists, ADM22-52.
      Conclusions: Increased macrophage infiltration and TNF-α expression in adipose tissue from GDM, but not from OBS, tissues stimulate ADM and its receptor overexpression, leading to enhanced lipolysis and hyperlipidemia. This might contribute to fetal macrosomia and adiposity in diabetic pregnancies.
    • References:
      Biol Reprod. 2015 Dec;93(6):136. (PMID: 26510869)
      ScientificWorldJournal. 2014;2014:926932. (PMID: 25202741)
      J Clin Endocrinol Metab. 2017 Sep 1;102(9):3425-3436. (PMID: 28666334)
      Clin Endocrinol (Oxf). 2012 Jan;76(1):2-11. (PMID: 21951069)
      Am J Physiol Endocrinol Metab. 2002 Mar;282(3):E522-33. (PMID: 11832353)
      Reprod Sci. 2009 Oct;16(10):921-37. (PMID: 19474287)
      Clin Chem Lab Med. 2013 Jan;51(1):177-85. (PMID: 23241684)
      Biol Reprod. 2015 Dec;93(6):134. (PMID: 26510864)
      Clin Obstet Gynecol. 2007 Dec;50(4):938-48. (PMID: 17982337)
      PLoS One. 2015 Aug 26;10(8):e0136892. (PMID: 26309121)
      Obstet Gynecol. 2001 May;97(5 Pt 1):776-80. (PMID: 11339933)
      Adv Exp Med Biol. 2017;960:327-343. (PMID: 28585206)
      Proc Nutr Soc. 2012 Nov;71(4):622-33. (PMID: 22914223)
      Acta Diabetol. 2008 Sep;45(3):157-65. (PMID: 18496643)
      J Clin Invest. 2003 Dec;112(12):1796-808. (PMID: 14679176)
      BMJ. 2014 Mar 11;348:g1567. (PMID: 24618099)
      PLoS One. 2012;7(8):e42943. (PMID: 22952622)
      Endokrynol Pol. 2014;65(2):134-42. (PMID: 24802737)
      J Clin Invest. 2007 Jan;117(1):175-84. (PMID: 17200717)
      Horm Metab Res. 2001 Aug;33(8):486-90. (PMID: 11544563)
      J Clin Invest. 2005 Mar;115(3):485-91. (PMID: 15765129)
      Am J Obstet Gynecol. 2014 May;210(5):431.e1-14. (PMID: 24361790)
      Diabetes. 2000 Dec;49(12):2208-11. (PMID: 11118027)
      Eur Cytokine Netw. 2006 Mar;17(1):4-12. (PMID: 16613757)
      Diabetes. 1985 Jun;34 Suppl 2:71-7. (PMID: 3922827)
      Lancet Diabetes Endocrinol. 2014 Jun;2(6):488-99. (PMID: 24731659)
      Cell. 2013 Feb 14;152(4):673-84. (PMID: 23415219)
      Best Pract Res Clin Endocrinol Metab. 2010 Aug;24(4):515-25. (PMID: 20832733)
      Lancet. 1997 Nov 15;350(9089):1449-50. (PMID: 9371176)
      J Clin Endocrinol Metab. 1998 Mar;83(3):847-50. (PMID: 9506738)
      Mol Cell Endocrinol. 2010 Mar 25;316(2):129-39. (PMID: 19723556)
      Diagn Mol Pathol. 2006 Mar;15(1):56-61. (PMID: 16531770)
    • Grant Information:
      R01 DK114689 United States DK NIDDK NIH HHS; R01 HD094347 United States HD NICHD NIH HHS; R01 HL058144 United States HL NHLBI NIH HHS; R21 HD091503 United States HD NICHD NIH HHS
    • Accession Number:
      0 (ADM protein, human)
      0 (Lipids)
      148498-78-6 (Adrenomedullin)
    • Publication Date:
      Date Created: 20180719 Date Completed: 20190521 Latest Revision: 20200306
    • Publication Date:
      20231215
    • Accession Number:
      PMC6456971
    • Accession Number:
      10.1210/jc.2018-00905
    • Accession Number:
      30020508