Saturated Fatty Acids Promote GDF15 Expression in Human Macrophages through the PERK/eIF2/CHOP Signaling Pathway

被引:26
作者
L'homme, Laurent [1 ,2 ]
Sermikli, Benan Pelin [1 ]
Staels, Bart [1 ]
Piette, Jacques [2 ]
Legrand-Poels, Sylvie [2 ]
Dombrowicz, David [1 ]
机构
[1] Univ Lille, Inst Pasteur Lille, CHU Lille, INSERM,U1011 EGID, F-59000 Lille, France
[2] Univ Liege, Lab Virol & Immunol, GIGA Signal Transduct, B-4000 Liege, Belgium
基金
欧洲研究理事会;
关键词
GDF15; macrophage; obesity; saturated fatty acids; stearate; ER stress; CHOP; DIFFERENTIATION FACTOR 15; ADIPOSE-TISSUE; INHIBITORY CYTOKINE-1; INSULIN-RESISTANCE; WEIGHT-LOSS; RECEPTOR; OBESITY; GROWTH; HOMEOSTASIS; BIOMARKER;
D O I
10.3390/nu12123771
中图分类号
R15 [营养卫生、食品卫生]; TS201 [基础科学];
学科分类号
100403 ;
摘要
Growth differentiation factor-15 (GDF-15) and its receptor GFRAL are both involved in the development of obesity and insulin resistance. Plasmatic GDF-15 level increases with obesity and is positively associated with disease progression. Despite macrophages have been recently suggested as a key source of GDF-15 in obesity, little is known about the regulation of GDF-15 in these cells. In the present work, we sought for potential pathophysiological activators of GDF15 expression in human macrophages and identified saturated fatty acids (SFAs) as strong inducers of GDF15 expression and secretion. SFAs increase GDF15 expression through the induction of an ER stress and the activation of the PERK/eIF2/CHOP signaling pathway in both PMA-differentiated THP-1 cells and in primary monocyte-derived macrophages. The transcription factor CHOP directly binds to the GDF15 promoter region and regulates GDF15 expression. Unlike SFAs, unsaturated fatty acids do not promote GDF15 expression and rather inhibit both SFA-induced GDF15 expression and ER stress. These results suggest that free fatty acids may be involved in the control of GDF-15 and provide new molecular insights about how diet and lipid metabolism may regulate the development of obesity and T2D.
引用
收藏
页码:1 / 15
页数:14
相关论文
共 46 条
  • [1] Growth differentiation factor 15 is positively associated with incidence of diabetes mellitus: the Malmo Diet and Cancer-Cardiovascular Cohort
    Bao, Xue
    Borne, Yan
    Muhammad, Iram Faqir
    Nilsson, Jan
    Lind, Lars
    Melander, Olle
    Niu, Kaijun
    Orho-Melander, Marju
    Engstrom, Gunnar
    [J]. DIABETOLOGIA, 2019, 62 (01) : 78 - 86
  • [2] Free fatty acids and pathogenesis of type 2 diabetes mellitus
    Bergman, RN
    Ader, M
    [J]. TRENDS IN ENDOCRINOLOGY AND METABOLISM, 2000, 11 (09) : 351 - 356
  • [3] Increase in endoplasmic reticulum stress-related proteins and genes in adipose tissue of obese, insulin-resistant individuals
    Boden, Guenther
    Duan, Xanbao
    Homko, Carol
    Molina, Ezequiel J.
    Song, WeiWei
    Perez, Oscar
    Cheung, Peter
    Merali, Salim
    [J]. DIABETES, 2008, 57 (09) : 2438 - 2444
  • [4] MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-beta superfamily
    Bootcov, MR
    Bauskin, AR
    Valenzuela, SM
    Moore, AG
    Bansal, M
    He, XY
    Zhang, HP
    Donnellan, M
    Mahler, S
    Pryor, K
    Walsh, BJ
    Nicholson, RC
    Fairlie, WD
    Por, SB
    Robbins, JM
    Breit, SN
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (21) : 11514 - 11519
  • [5] Brown DA, 2003, CLIN CANCER RES, V9, P2642
  • [6] Concentration in plasma of macrophage inhibitory cytokine-1 and risk of cardiovascular events in women: a nested case-control study
    Brown, DA
    Breit, SN
    Buring, J
    Fairlie, WD
    Bauskin, AR
    Liu, T
    Ridker, PM
    [J]. LANCET, 2002, 359 (9324) : 2159 - 2163
  • [7] NAG-1/GDF-15 prevents obesity by increasing thermogenesis, lipolysis and oxidative metabolism
    Chrysovergis, K.
    Wang, X.
    Kosak, J.
    Lee, S-H
    Kim, J. S.
    Foley, J. F.
    Travlos, G.
    Singh, S.
    Baek, S. J.
    Eling, T. E.
    [J]. INTERNATIONAL JOURNAL OF OBESITY, 2014, 38 (12) : 1555 - 1564
  • [8] Growth differentiation factor 15 is a myomitokine governing systemic energy homeostasis
    Chung, Hyo Kyun
    Ryu, Dongryeol
    Kim, Koon Soon
    Chang, Joon Young
    Kim, Yong Kyung
    Yi, Hyon-Seung
    Kang, Seul Gi
    Choi, Min Jeong
    Lee, Seong Eun
    Jung, Saet-Byel
    Ryu, Min Jeong
    Kim, Soung Jung
    Kweon, Gi Ryang
    Kim, Hail
    Hwang, Jung Hwan
    Lee, Chul-Ho
    Lee, Se-Jin
    Wall, Christopher E.
    Downes, Michael
    Evans, Ronald M.
    Auwerx, Johan
    Shong, Minho
    [J]. JOURNAL OF CELL BIOLOGY, 2017, 216 (01) : 149 - 165
  • [9] Evidence Based Selection of Housekeeping Genes
    de Jonge, Hendrik J. M.
    Fehrmann, Rudolf S. N.
    de Bont, Eveline S. J. M.
    Hofstra, Robert M. W.
    Gerbens, Frans
    Kamps, Willem A.
    de Vries, Elisabeth G. E.
    van der Zee, Ate G. J.
    Meerman, Gerard J. te
    ter Elst, Arja
    [J]. PLOS ONE, 2007, 2 (09):
  • [10] Identification of Macrophage Inhibitory Cytokine-1 in Adipose Tissue and Its Secretion as an Adipokine by Human Adipocytes
    Ding, Qi
    Mracek, Tomas
    Gonzalez-Muniesa, Pedro
    Kos, Katarina
    Wilding, John
    Trayhurn, Paul
    Bing, Chen
    [J]. ENDOCRINOLOGY, 2009, 150 (04) : 1688 - 1696