Dectin-1 Activation Exacerbates Obesity and Insulin Resistance in the Absence of MyD88

Angela Castoldi (Corresponding Author), Vinicius Andrade-Oliveira, Cristhiane Favero Aguiar, Mariane Tami Amano, Jennifer Lee, Marcelli Terumi Miyagi, Marcela Teatin Latância, Tarcio Teodoro Braga, Marina Burgos da Silva, Aline Ignácio, Joanna Darck Carola C. Lima, Flávio V Loures, José Antonio T. Albuquerque, Marina Barguil Macêdo, Rafael Ribeiro Almeida, Jonas W. Gaiarsa, Luis A. Luévano Martínez, Thiago Belchior, Meire Ioshie Hiyane, Gordon D BrownMarcelo A. Mori, Christian Hoffmann, Marília Seelaender, Willian T. Festuccia, Pedro Manoel Moraes-Vieira, Niels Olsen Saraiva Câmara

Research output: Contribution to journalArticle

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Abstract

Highlights
•MyD88 absence upregulates Dectin-1 in adipose tissue (AT) and AT macrophages (ATMs)
•Dectin-1 inhibition decreases CD11c+ ATMs and protects mice from insulin resistance (IR)
•Dectin-1 activation increases CD11c+ ATMs and worsens IR
•Obese humans have increased Dectin-1 expression in AT
Summary
The underlying mechanism by which MyD88 regulates the development of obesity, metainflammation, and insulin resistance (IR) remains unknown. Global deletion of MyD88 in high-fat diet (HFD)-fed mice resulted in increased weight gain, impaired glucose homeostasis, elevated Dectin-1 expression in adipose tissue (AT), and proinflammatory CD11c+ AT macrophages (ATMs). Dectin-1 KO mice were protected from diet-induced obesity (DIO) and IR and had reduced CD11c+ AT macrophages. Dectin-1 antagonist improved glucose homeostasis and decreased CD11c+ AT macrophages in chow- and HFD-fed MyD88 KO mice. Dectin-1 agonist worsened glucose homeostasis in MyD88 KO mice. Dectin-1 expression is increased in AT from obese individuals. Together, our data indicate that Dectin-1 regulates AT inflammation by promoting CD11c+ AT macrophages in the absence of MyD88 and identify a role for Dectin-1 in chronic inflammatory states, such as obesity. This suggests that Dectin-1 may have therapeutic implications as a biomarker for metabolic dysregulation in humans.
Original languageEnglish
Pages (from-to)2272-2288
Number of pages7
JournalCell Reports
Volume19
Issue number11
DOIs
Publication statusPublished - 13 Jun 2017

Fingerprint

Insulin Resistance
Obesity
Chemical activation
Insulin
Macrophages
Adipose Tissue
Tissue
Nutrition
Homeostasis
High Fat Diet
Glucose
dectin 1
Fats
Biomarkers
Weight Gain
Up-Regulation
Diet
Inflammation

Keywords

  • MyD88
  • Dectin-1
  • insulin resistance
  • inflammation
  • macrophage
  • adipose tissue

Cite this

Castoldi, A., Andrade-Oliveira, V., Aguiar, C. F., Amano, M. T., Lee, J., Miyagi, M. T., ... Câmara, N. O. S. (2017). Dectin-1 Activation Exacerbates Obesity and Insulin Resistance in the Absence of MyD88. Cell Reports, 19(11), 2272-2288. https://doi.org/10.1016/j.celrep.2017.05.059

Dectin-1 Activation Exacerbates Obesity and Insulin Resistance in the Absence of MyD88. / Castoldi, Angela (Corresponding Author); Andrade-Oliveira, Vinicius ; Aguiar, Cristhiane Favero ; Amano, Mariane Tami ; Lee, Jennifer; Miyagi, Marcelli Terumi ; Latância, Marcela Teatin ; Braga, Tarcio Teodoro ; da Silva, Marina Burgos; Ignácio, Aline ; Lima, Joanna Darck Carola C. ; Loures, Flávio V; Albuquerque, José Antonio T. ; Macêdo, Marina Barguil ; Almeida, Rafael Ribeiro ; Gaiarsa, Jonas W. ; Martínez, Luis A. Luévano ; Belchior, Thiago ; Hiyane, Meire Ioshie; Brown, Gordon D; Mori, Marcelo A. ; Hoffmann, Christian; Seelaender, Marília ; Festuccia, Willian T. ; Moraes-Vieira, Pedro Manoel; Câmara, Niels Olsen Saraiva .

In: Cell Reports, Vol. 19, No. 11, 13.06.2017, p. 2272-2288.

Research output: Contribution to journalArticle

Castoldi, A, Andrade-Oliveira, V, Aguiar, CF, Amano, MT, Lee, J, Miyagi, MT, Latância, MT, Braga, TT, da Silva, MB, Ignácio, A, Lima, JDCC, Loures, FV, Albuquerque, JAT, Macêdo, MB, Almeida, RR, Gaiarsa, JW, Martínez, LAL, Belchior, T, Hiyane, MI, Brown, GD, Mori, MA, Hoffmann, C, Seelaender, M, Festuccia, WT, Moraes-Vieira, PM & Câmara, NOS 2017, 'Dectin-1 Activation Exacerbates Obesity and Insulin Resistance in the Absence of MyD88', Cell Reports, vol. 19, no. 11, pp. 2272-2288. https://doi.org/10.1016/j.celrep.2017.05.059
Castoldi A, Andrade-Oliveira V, Aguiar CF, Amano MT, Lee J, Miyagi MT et al. Dectin-1 Activation Exacerbates Obesity and Insulin Resistance in the Absence of MyD88. Cell Reports. 2017 Jun 13;19(11):2272-2288. https://doi.org/10.1016/j.celrep.2017.05.059
Castoldi, Angela ; Andrade-Oliveira, Vinicius ; Aguiar, Cristhiane Favero ; Amano, Mariane Tami ; Lee, Jennifer ; Miyagi, Marcelli Terumi ; Latância, Marcela Teatin ; Braga, Tarcio Teodoro ; da Silva, Marina Burgos ; Ignácio, Aline ; Lima, Joanna Darck Carola C. ; Loures, Flávio V ; Albuquerque, José Antonio T. ; Macêdo, Marina Barguil ; Almeida, Rafael Ribeiro ; Gaiarsa, Jonas W. ; Martínez, Luis A. Luévano ; Belchior, Thiago ; Hiyane, Meire Ioshie ; Brown, Gordon D ; Mori, Marcelo A. ; Hoffmann, Christian ; Seelaender, Marília ; Festuccia, Willian T. ; Moraes-Vieira, Pedro Manoel ; Câmara, Niels Olsen Saraiva . / Dectin-1 Activation Exacerbates Obesity and Insulin Resistance in the Absence of MyD88. In: Cell Reports. 2017 ; Vol. 19, No. 11. pp. 2272-2288.
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title = "Dectin-1 Activation Exacerbates Obesity and Insulin Resistance in the Absence of MyD88",
abstract = "Highlights•MyD88 absence upregulates Dectin-1 in adipose tissue (AT) and AT macrophages (ATMs)•Dectin-1 inhibition decreases CD11c+ ATMs and protects mice from insulin resistance (IR)•Dectin-1 activation increases CD11c+ ATMs and worsens IR•Obese humans have increased Dectin-1 expression in ATSummaryThe underlying mechanism by which MyD88 regulates the development of obesity, metainflammation, and insulin resistance (IR) remains unknown. Global deletion of MyD88 in high-fat diet (HFD)-fed mice resulted in increased weight gain, impaired glucose homeostasis, elevated Dectin-1 expression in adipose tissue (AT), and proinflammatory CD11c+ AT macrophages (ATMs). Dectin-1 KO mice were protected from diet-induced obesity (DIO) and IR and had reduced CD11c+ AT macrophages. Dectin-1 antagonist improved glucose homeostasis and decreased CD11c+ AT macrophages in chow- and HFD-fed MyD88 KO mice. Dectin-1 agonist worsened glucose homeostasis in MyD88 KO mice. Dectin-1 expression is increased in AT from obese individuals. Together, our data indicate that Dectin-1 regulates AT inflammation by promoting CD11c+ AT macrophages in the absence of MyD88 and identify a role for Dectin-1 in chronic inflammatory states, such as obesity. This suggests that Dectin-1 may have therapeutic implications as a biomarker for metabolic dysregulation in humans.",
keywords = "MyD88, Dectin-1, insulin resistance, inflammation, macrophage , adipose tissue",
author = "Angela Castoldi and Vinicius Andrade-Oliveira and Aguiar, {Cristhiane Favero} and Amano, {Mariane Tami} and Jennifer Lee and Miyagi, {Marcelli Terumi} and Lat{\^a}ncia, {Marcela Teatin} and Braga, {Tarcio Teodoro} and {da Silva}, {Marina Burgos} and Aline Ign{\'a}cio and Lima, {Joanna Darck Carola C.} and Loures, {Fl{\'a}vio V} and Albuquerque, {Jos{\'e} Antonio T.} and Mac{\^e}do, {Marina Barguil} and Almeida, {Rafael Ribeiro} and Gaiarsa, {Jonas W.} and Mart{\'i}nez, {Luis A. Lu{\'e}vano} and Thiago Belchior and Hiyane, {Meire Ioshie} and Brown, {Gordon D} and Mori, {Marcelo A.} and Christian Hoffmann and Mar{\'i}lia Seelaender and Festuccia, {Willian T.} and Moraes-Vieira, {Pedro Manoel} and C{\^a}mara, {Niels Olsen Saraiva}",
note = "This work was supported by Funda{\cc}{\~a}o de Amparo {\`a} Pesquisa do Estado de S{\~a}o Paulo (FAPESP, grant numbers 11/15682-4, 12/02270-2, 15/18121-4), Conselho Nacional de Desenvolvimento Cient{\'i}fico e Tecnol{\'o}gico (CNPq, Regenera INCT Process Grant 465656/2014-5). JL is funded by the NIH/NIDDK R01DK106210. GDB is funded by the Wellcome Trust and the MRC Centre for Medical Mycology. Open access journal",
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T1 - Dectin-1 Activation Exacerbates Obesity and Insulin Resistance in the Absence of MyD88

AU - Castoldi, Angela

AU - Andrade-Oliveira, Vinicius

AU - Aguiar, Cristhiane Favero

AU - Amano, Mariane Tami

AU - Lee, Jennifer

AU - Miyagi, Marcelli Terumi

AU - Latância, Marcela Teatin

AU - Braga, Tarcio Teodoro

AU - da Silva, Marina Burgos

AU - Ignácio, Aline

AU - Lima, Joanna Darck Carola C.

AU - Loures, Flávio V

AU - Albuquerque, José Antonio T.

AU - Macêdo, Marina Barguil

AU - Almeida, Rafael Ribeiro

AU - Gaiarsa, Jonas W.

AU - Martínez, Luis A. Luévano

AU - Belchior, Thiago

AU - Hiyane, Meire Ioshie

AU - Brown, Gordon D

AU - Mori, Marcelo A.

AU - Hoffmann, Christian

AU - Seelaender, Marília

AU - Festuccia, Willian T.

AU - Moraes-Vieira, Pedro Manoel

AU - Câmara, Niels Olsen Saraiva

N1 - This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, grant numbers 11/15682-4, 12/02270-2, 15/18121-4), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Regenera INCT Process Grant 465656/2014-5). JL is funded by the NIH/NIDDK R01DK106210. GDB is funded by the Wellcome Trust and the MRC Centre for Medical Mycology. Open access journal

PY - 2017/6/13

Y1 - 2017/6/13

N2 - Highlights•MyD88 absence upregulates Dectin-1 in adipose tissue (AT) and AT macrophages (ATMs)•Dectin-1 inhibition decreases CD11c+ ATMs and protects mice from insulin resistance (IR)•Dectin-1 activation increases CD11c+ ATMs and worsens IR•Obese humans have increased Dectin-1 expression in ATSummaryThe underlying mechanism by which MyD88 regulates the development of obesity, metainflammation, and insulin resistance (IR) remains unknown. Global deletion of MyD88 in high-fat diet (HFD)-fed mice resulted in increased weight gain, impaired glucose homeostasis, elevated Dectin-1 expression in adipose tissue (AT), and proinflammatory CD11c+ AT macrophages (ATMs). Dectin-1 KO mice were protected from diet-induced obesity (DIO) and IR and had reduced CD11c+ AT macrophages. Dectin-1 antagonist improved glucose homeostasis and decreased CD11c+ AT macrophages in chow- and HFD-fed MyD88 KO mice. Dectin-1 agonist worsened glucose homeostasis in MyD88 KO mice. Dectin-1 expression is increased in AT from obese individuals. Together, our data indicate that Dectin-1 regulates AT inflammation by promoting CD11c+ AT macrophages in the absence of MyD88 and identify a role for Dectin-1 in chronic inflammatory states, such as obesity. This suggests that Dectin-1 may have therapeutic implications as a biomarker for metabolic dysregulation in humans.

AB - Highlights•MyD88 absence upregulates Dectin-1 in adipose tissue (AT) and AT macrophages (ATMs)•Dectin-1 inhibition decreases CD11c+ ATMs and protects mice from insulin resistance (IR)•Dectin-1 activation increases CD11c+ ATMs and worsens IR•Obese humans have increased Dectin-1 expression in ATSummaryThe underlying mechanism by which MyD88 regulates the development of obesity, metainflammation, and insulin resistance (IR) remains unknown. Global deletion of MyD88 in high-fat diet (HFD)-fed mice resulted in increased weight gain, impaired glucose homeostasis, elevated Dectin-1 expression in adipose tissue (AT), and proinflammatory CD11c+ AT macrophages (ATMs). Dectin-1 KO mice were protected from diet-induced obesity (DIO) and IR and had reduced CD11c+ AT macrophages. Dectin-1 antagonist improved glucose homeostasis and decreased CD11c+ AT macrophages in chow- and HFD-fed MyD88 KO mice. Dectin-1 agonist worsened glucose homeostasis in MyD88 KO mice. Dectin-1 expression is increased in AT from obese individuals. Together, our data indicate that Dectin-1 regulates AT inflammation by promoting CD11c+ AT macrophages in the absence of MyD88 and identify a role for Dectin-1 in chronic inflammatory states, such as obesity. This suggests that Dectin-1 may have therapeutic implications as a biomarker for metabolic dysregulation in humans.

KW - MyD88

KW - Dectin-1

KW - insulin resistance

KW - inflammation

KW - macrophage

KW - adipose tissue

U2 - 10.1016/j.celrep.2017.05.059

DO - 10.1016/j.celrep.2017.05.059

M3 - Article

VL - 19

SP - 2272

EP - 2288

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 11

ER -