Protection from diet‐induced obesity and insulin resistance in mice lacking CCL19‐CCR7 signaling

• Published in: Obesity (Silver Spring, Md.) Md.), 2015-07, Vol.23 (7), p.1460-1471
• Main Authors: Sano, Tomomi, Iwashita, Misaki, Nagayasu, Shintaro, Yamashita, Akiko, Shinjo, Takanori, Hashikata, Atsushi, Asano, Tomoichiro, Kushiyama, Akifumi, Ishimaru, Naozumi, Takahama, Yousuke, Nishimura, Fusanori
• Format: Article
• Language: English
• Subjects: Adipocytes; Adipocytes - metabolism; Adipose Tissue - metabolism; Age; Animals; Chemokine CCL19 - metabolism; Chemokine CCL7 - metabolism; Chemokines; Disease Models, Animal; Experiments; Fatty acids; Gene expression; Inflammation; Inflammation - metabolism; Insulin; Insulin resistance; Insulin Resistance - physiology; Kinases; Ligands; Lymphocytes; Macrophages - metabolism; Mice; Mice, Obese - metabolism; Monocytes - metabolism; Obesity; Obesity - metabolism; Proteins; Rodents; Signal Transduction; Studies; Tumor necrosis factor-TNF
• ISSN: 1930-7381; 1930-739X
• DOI: 10.1002/oby.21127

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.