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- Title
Macrophage VLDLR mediates obesity-induced insulin resistance with adipose tissue inflammation.
- Authors
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
- Abstract
Obesity is closely associated with increased adipose tissue macrophages (ATMs), which contribute to systemic insulin resistance and altered lipid metabolism by creating a proinflammatory 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 proinflammatory 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.
- Subjects
INSULIN resistance; ADIPOSE tissues; GLUCOSE intolerance; LIPOPROTEIN receptors; BONE marrow; LIPID metabolism
- Publication
Nature Communications, 2017, Vol 8, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-017-01232-w