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.