title: CXCL14 deficiency in mice attenuates obesity and inhibits feeding behavior in a novel environment.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Stem Cell Project group, The Tokyo Metropolitan Institute of Medical Science, Tokyo Metropolitan Organization for Medical Research, Kamikitazawa, Setagaya-ku, Tokyo, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Tanegashima
authors.forename: Shiki
authors.initials: S
authors.lastname: Okamoto
authors.forename: Yuki
authors.initials: Y
authors.lastname: Nakayama
authors.forename: Choji
authors.initials: C
authors.lastname: Taya
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shitara
authors.forename: Rie
authors.initials: R
authors.lastname: Ishii
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Yonekawa
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Minokoshi
authors.forename: Takahiko
authors.initials: T
authors.lastname: Hara
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D019743:Chemokines, CXC / Q000008:administration & dosage / Q000172:deficiency* / Q000502:physiology; D004435:Eating / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects*; D005260:Female; D007031:Hypothalamus / Q000378:metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000209:etiology*; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: C517518:CXCL14 protein, mouse; D019743:Chemokines, CXC; D011994:Recombinant Proteins