title: Protection from diet-induced obesity and insulin resistance in mice lacking CCL19-CCR7 signaling.
abstract: OBJECTIVE
  Several chemokines play important roles in recruiting the monocyte/macrophage lineage into adipose tissues. We previously found CCL19 was highly expressed in adipocytes cocultured with macrophages stimulated by endotoxin. This study aimed to evaluate the role of CCL19-CCR7 axis on obesity and insulin resistance.
  
  
  METHODS
  Serum CCL19 concentration was examined in obese model mice challenged by endotoxin. CCL19 receptor-null, Ccr7(-/-), mice and wild-type mice fed a high-fat diet or normal diet were used to investigate the role of CCL19 signals on obesity-associated inflammation.
  
  
  RESULTS
  CCL19 protein was elevated in the sera of obese model mice challenged by endotoxin. Ccr7(-/-) mice were protected from diet-induced obesity and insulin resistance. The adipose tissue and liver expression of inflammatory genes of Ccr7(-/-) mice was much lower than in diet-induced obese mice. Ccr7(-/-) mice were protected from fatty liver and dyslipidemia and exhibited increased thermogenesis on high-fat feeding. CCL19 attracts activated dendritic cells (DC). The expression of the DC markers, CD11b and 11c, was not observed in the adipose tissues of Ccr7(-/-) mice fed a high-fat diet, which might be closely associated with the protection of these mice from obesity.
  
  
  CONCLUSIONS
  The CCL19-CCR7 pathway associates with the development of high-fat-induced obesity and insulin resistance.
authors.affiliation: Department of Dental Science for Health Promotion, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Sano
authors.affiliation: Section of Periodontology, Kyushu University Faculty of Dental Science, Fukuoka, Japan.
authors.forename: Misaki
authors.initials: M
authors.lastname: Iwashita
authors.affiliation: Department of Dental Science for Health Promotion, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Nagayasu
authors.affiliation: Section of Periodontology, Kyushu University Faculty of Dental Science, Fukuoka, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Yamashita
authors.affiliation: Section of Periodontology, Kyushu University Faculty of Dental Science, Fukuoka, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Shinjo
authors.affiliation: Department of Dental Science for Health Promotion, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hashikata
authors.affiliation: Department of Biological Chemistry, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
authors.forename: Tomoichiro
authors.initials: T
authors.lastname: Asano
authors.affiliation: Division of Metabolic Diseases, The Institute for Adult Diseases, Asahi Life Foundation, Tokyo, Japan.
authors.forename: Akifumi
authors.initials: A
authors.lastname: Kushiyama
authors.affiliation: Department of Oral Molecular Pathology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Naozumi
authors.initials: N
authors.lastname: Ishimaru
authors.affiliation: Division of Experimental Immunology, Institute for Genome Research, the University of Tokushima, Tokushima, Japan.
authors.forename: Yousuke
authors.initials: Y
authors.lastname: Takahama
authors.affiliation: Section of Periodontology, Kyushu University Faculty of Dental Science, Fukuoka, Japan.
authors.forename: Fusanori
authors.initials: F
authors.lastname: Nishimura
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D054415:Chemokine CCL19 / Q000378:metabolism*; D054410:Chemokine CCL7 / Q000378:metabolism*; D004195:Disease Models, Animal; D007249:Inflammation / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008820:Mice, Obese / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C515461:Ccl19 protein, mouse; C515451:Ccl7 protein, mouse; D054415:Chemokine CCL19; D054410:Chemokine CCL7