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

Angela  Castoldi; 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 Brown; Marcelo A.  Mori; Christian Hoffmann; Marília  Seelaender; Willian T.  Festuccia; Pedro Manoel Moraes-Vieira; Niels Olsen Saraiva  Câmara

doi:10.1016/j.celrep.2017.05.059

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

Applied Medicine

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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 language	English
Pages (from-to)	2272-2288
Number of pages	7
Journal	Cell Reports
Volume	19
Issue number	11
DOIs	https://doi.org/10.1016/j.celrep.2017.05.059
Publication status	Published - 13 Jun 2017

Bibliographical note

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

Keywords

MyD88
Dectin-1
insulin resistance
inflammation
macrophage
adipose tissue

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Dectin-1 Activation Exacerbates Obesity and Insulin Resistance in the Absence of MyD88
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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Castoldi, A., Andrade-Oliveira, V., Aguiar, C. F., Amano, M. T., Lee, J., Miyagi, M. T., Latância, M. T., Braga, T. T., da Silva, M. B., Ignácio, A., Lima, J. D. C. C., Loures, F. V., Albuquerque, J. A. T., Macêdo, M. B., Almeida, R. R., Gaiarsa, J. W., Martínez, L. A. L., Belchior, T., Hiyane, M. I., ... 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

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

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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{\c c}{\~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",

year = "2017",

month = jun,

day = "13",

doi = "10.1016/j.celrep.2017.05.059",

language = "English",

volume = "19",

pages = "2272--2288",

journal = "Cell Reports",

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number = "11",

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TY - JOUR

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

SN - 2211-1247

VL - 19

SP - 2272

EP - 2288

JO - Cell Reports

JF - Cell Reports

IS - 11

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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