title: Very low density lipoprotein receptor (VLDLR) expression is a determinant factor in adipose tissue inflammation and adipocyte-macrophage interaction.
abstract: Obesity is associated with adipose tissue remodeling, characterized by adipocyte hypertrophy and macrophage infiltration. Previously, we have shown that very low density lipoprotein receptor (VLDLR) is virtually absent in preadipocytes but is strongly induced during adipogenesis and actively participates in adipocyte hypertrophy. In this study, we investigated the role of VLDLR in adipose tissue inflammation and adipocyte-macrophage interactions in wild type and VLDLR-deficient mice fed a high fat diet. The results show that VLDLR deficiency reduced high fat diet-induced inflammation and endoplasmic reticulum (ER) stress in adipose tissue in conjunction with reduced macrophage infiltration, especially those expressing pro-inflammatory markers. In adipocyte culture, VLDLR deficiency prevented adipocyte hypertrophy and strongly reduced VLDL-induced ER stress and inflammation. Likewise, cultures of primary peritoneal macrophages show that VLDLR deficiency reduced lipid accumulation and inflammation but did not alter chemotactic response of macrophages to adipocyte signals. Moreover, VLDLR deficiency tempered the synergistic inflammatory interactions between adipocytes and macrophages in a co-culture system. Collectively, these results show that VLDLR contributes to adipose tissue inflammation and mediates VLDL-induced lipid accumulation and induction of inflammation and ER stress in adipocytes and macrophages.
authors.affiliation: From the Department of Surgery, Hackensack University Medical Center, Hackensack, New Jersey 07601 and.
authors.forename: Andrew
authors.initials: A
authors.lastname: Nguyen
authors.forename: Huan
authors.initials: H
authors.lastname: Tao
authors.forename: Michael
authors.initials: M
authors.lastname: Metrione
authors.forename: Tahar
authors.initials: T
authors.lastname: Hajri
mesh_terms: D017667:Adipocytes / Q000378:metabolism* / Q000473:pathology; D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002450:Cell Communication / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D018920:Coculture Techniques; D004041:Dietary Fats / Q000009:adverse effects / Q000494:pharmacology; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D008079:Lipoproteins, VLDL / Q000235:genetics / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D015434:Panniculitis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011973:Receptors, LDL / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D004041:Dietary Fats; D008079:Lipoproteins, VLDL; D011973:Receptors, LDL; C036053:VLDL receptor
keywords: Adipocyte; Adipose Tissue; Inflammation; Macrophages; Obesity; VLDLR