Macrophage VLDLR mediates obesity-induced insulin resistance with adipose tissue inflammation

Kyung Cheul Shin, Injae Hwang, Sung Sik Choe, Jeu Park, Yul Ji, Jong In Kim, Gha Young Lee, Sung Hee Choi, Jianhong Ching, Jean Paul Kovalik, Jae Bum Kim

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Obesity is closely associated with increased adipose tissue macrophages (ATMs), which contribute to systemic insulin resistance and altered lipid metabolism by creating a pro-inflammatory environment. Very low-density lipoprotein receptor (VLDLR) is involved in lipoprotein uptake and storage. However, whether lipid uptake via VLDLR in macrophages affects obesity-induced inflammatory responses and insulin resistance is not well understood. Here we show that elevated VLDLR expression in ATMs promotes adipose tissue inflammation and glucose intolerance in obese mice. In macrophages, VLDL treatment upregulates intracellular levels of C16:0 ceramides in a VLDLR-dependent manner, which potentiates pro-inflammatory responses and promotes M1-like macrophage polarization. Adoptive transfer of VLDLR knockout bone marrow to wild-type mice relieves adipose tissue inflammation and improves insulin resistance in diet-induced obese mice. These findings suggest that increased VLDL-VLDLR signaling in ATMs aggravates adipose tissue inflammation and insulin resistance in obesity.

Original languageEnglish
Article number1087
JournalNature Communications
Volume8
Issue number1
DOIs
StatePublished - 1 Dec 2017

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obesity
adipose tissues
lipoproteins
insulin
macrophages
Macrophages
Insulin Resistance
Adipose Tissue
Obesity
Insulin
Tissue
Inflammation
Obese Mice
mice
lipid metabolism
Glucose Intolerance
Adoptive Transfer
Ceramides
diets
Nutrition

Cite this

Shin, K. C., Hwang, I., Choe, S. S., Park, J., Ji, Y., Kim, J. I., ... Kim, J. B. (2017). Macrophage VLDLR mediates obesity-induced insulin resistance with adipose tissue inflammation. Nature Communications, 8(1), [1087]. https://doi.org/10.1038/s41467-017-01232-w
Shin, Kyung Cheul ; Hwang, Injae ; Choe, Sung Sik ; Park, Jeu ; Ji, Yul ; Kim, Jong In ; Lee, Gha Young ; Choi, Sung Hee ; Ching, Jianhong ; Kovalik, Jean Paul ; Kim, Jae Bum. / Macrophage VLDLR mediates obesity-induced insulin resistance with adipose tissue inflammation. In: Nature Communications. 2017 ; Vol. 8, No. 1.
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abstract = "Obesity is closely associated with increased adipose tissue macrophages (ATMs), which contribute to systemic insulin resistance and altered lipid metabolism by creating a pro-inflammatory environment. Very low-density lipoprotein receptor (VLDLR) is involved in lipoprotein uptake and storage. However, whether lipid uptake via VLDLR in macrophages affects obesity-induced inflammatory responses and insulin resistance is not well understood. Here we show that elevated VLDLR expression in ATMs promotes adipose tissue inflammation and glucose intolerance in obese mice. In macrophages, VLDL treatment upregulates intracellular levels of C16:0 ceramides in a VLDLR-dependent manner, which potentiates pro-inflammatory responses and promotes M1-like macrophage polarization. Adoptive transfer of VLDLR knockout bone marrow to wild-type mice relieves adipose tissue inflammation and improves insulin resistance in diet-induced obese mice. These findings suggest that increased VLDL-VLDLR signaling in ATMs aggravates adipose tissue inflammation and insulin resistance in obesity.",
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Shin, KC, Hwang, I, Choe, SS, Park, J, Ji, Y, Kim, JI, Lee, GY, Choi, SH, Ching, J, Kovalik, JP & Kim, JB 2017, 'Macrophage VLDLR mediates obesity-induced insulin resistance with adipose tissue inflammation', Nature Communications, vol. 8, no. 1, 1087. https://doi.org/10.1038/s41467-017-01232-w

Macrophage VLDLR mediates obesity-induced insulin resistance with adipose tissue inflammation. / Shin, Kyung Cheul; Hwang, Injae; Choe, Sung Sik; Park, Jeu; Ji, Yul; Kim, Jong In; Lee, Gha Young; Choi, Sung Hee; Ching, Jianhong; Kovalik, Jean Paul; Kim, Jae Bum.

In: Nature Communications, Vol. 8, No. 1, 1087, 01.12.2017.

Research output: Contribution to journalArticle

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AU - Kim, Jong In

AU - Lee, Gha Young

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