CXCL14 deficiency in mice attenuates obesity and inhibits feeding behavior in a novel environment

CXCL14 is a chemoattractant for macrophages and immature dendritic cells. We recently reported that CXCL14-deficient (CXCL14(-/-)) female mice in the mixed background are protected from obesity-induced hyperglycemia and insulin resistance. The decreased macrophage infiltration into visceral adipose tissues and the increased insulin sensitivity of skeletal muscle contributed to these phenotypes.

In this study, we performed a comprehensive study for the body weight control of CXCL14(-/-) mice in the C57BL/6 background. We show that both male and female CXCL14(-/-) mice have a 7-11% lower body weight compared to CXCL14(+/-) and CXCL14(+/+) mice in adulthood. This is mainly caused by decreased food intake, and not by increased energy expenditure or locomotor activity. Reduced body weight resulting from the CXCL14 deficiency was more pronounced in double mutant CXCL14(-/-)ob/ob and CXCL14(-/-)A(y) mice. In the case of CXCL14(-/-)A(y) mice, oxygen consumption was increased compared to CXCL14(+/-)A(y) mice, in addition to the reduced food intake. In CXCL14(-/-) mice, fasting-induced up-regulation of Npy and Agrp mRNAs in the hypothalamus was blunted. As intracerebroventricular injection of recombinant CXCL14 did not change the food intake of CXCL14(-/-) mice, CXCL14 could indirectly regulate appetite. Intriguingly, the food intake of CXCL14(-/-) mice was significantly repressed when mice were transferred to a novel environment.

We demonstrated that CXCL14 is involved in the body weight control leading to the fully obese phenotype in leptin-deficient or A(y) mutant mice. In addition, we obtained evidence indicating that CXCL14 may play an important role in central nervous system regulation of feeding behavior.