PMID- 30992469
OWN - NLM
STAT- MEDLINE
DCOM- 20201013
LR  - 20210109
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 9
IP  - 1
DP  - 2019 Apr 16
TI  - CXCL12-CXCR4 pathway activates brown adipocytes and induces insulin resistance in 
      CXCR4-deficient mice under high-fat diet.
PG  - 6165
LID - 10.1038/s41598-019-42127-8 [doi]
LID - 6165
AB  - Brown adipose tissue (BAT) plays a role in energy expenditure and is involved in 
      nutrient metabolism. C-X-C chemokine ligand 12 (CXCL12)-CXCR4 pathway regulates 
      the immune, nervous, and cardiovascular systems and affects the adipose tissue. 
      Here, we investigated the role of this pathway as an activator of BAT. Uncoupling 
      protein 1 mRNA and protein levels and oxygen consumption increased in the brown 
      adipocytes treated with 100 nM CXCL12 peptide. CXCL12-mediated upregulation in 
      P38 and extracellular signal-regulated kinase (ERK) levels was reduced by each 
      inhibitor. Thus, the CXCL12-CXCR4 pathway activated the brown adipocytes through 
      P38 and ERK that acted downstream of this pathway. Mice with CXCR4 defects only 
      in the brown adipocytes were generated and fed with high-fat diet (HFD). Body 
      weight and blood glucose after glucose injection increased in these mice. 
      Long-term exposure to HFD deteriorated blood glucose level after glucose 
      injection. Insulin sensitivity was exacerbated in the knockout mice fed with HFD. 
      Serum lipid parameters and CXCL12 level in knockout mice were similar to those in 
      control mice. These results suggest that the CXCL12-CXCR4 pathway induces brown 
      adipocyte activity and affects nutrient metabolism under HFD load.
FAU - Kurita, Kenichi
AU  - Kurita K
AD  - Department of Endocrinology, Hematology and Gerontology, Chiba University 
      Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
AD  - Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, 
      1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
FAU - Ishikawa, Ko
AU  - Ishikawa K
AD  - Department of Endocrinology, Hematology and Gerontology, Chiba University 
      Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan. 
      ishikawako1225@gmail.com.
AD  - Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, 
      1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan. ishikawako1225@gmail.com.
FAU - Takeda, Kenji
AU  - Takeda K
AD  - Department of Endocrinology, Hematology and Gerontology, Chiba University 
      Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
AD  - Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, 
      1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
FAU - Fujimoto, Masanori
AU  - Fujimoto M
AD  - Department of Endocrinology, Hematology and Gerontology, Chiba University 
      Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
AD  - Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, 
      1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
FAU - Ono, Hiraku
AU  - Ono H
AD  - Department of Endocrinology, Hematology and Gerontology, Chiba University 
      Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
AD  - Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, 
      1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
FAU - Kumagai, Jin
AU  - Kumagai J
AD  - Department of Endocrinology, Hematology and Gerontology, Chiba University 
      Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
AD  - Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, 
      1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
FAU - Inoue, Hiromi
AU  - Inoue H
AD  - Department of Endocrinology, Hematology and Gerontology, Chiba University 
      Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
AD  - Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, 
      1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
FAU - Yokoh, Hidetaka
AU  - Yokoh H
AD  - Department of Endocrinology, Hematology and Gerontology, Chiba University 
      Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
AD  - Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, 
      1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
FAU - Yokote, Koutaro
AU  - Yokote K
AD  - Department of Endocrinology, Hematology and Gerontology, Chiba University 
      Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
AD  - Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, 
      1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190416
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (CXCR4 protein, mouse)
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Cxcl12 protein, mouse)
RN  - 0 (Receptors, CXCR4)
SB  - IM
MH  - Adipocytes, Brown/*metabolism
MH  - Animals
MH  - Cells, Cultured
MH  - Chemokine CXCL12/*metabolism
MH  - Diet, High-Fat/adverse effects
MH  - Energy Metabolism
MH  - Gene Deletion
MH  - *Insulin Resistance
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Receptors, CXCR4/genetics/*metabolism
MH  - *Signal Transduction
PMC - PMC6467900
COIS- The authors declare no competing interests.
EDAT- 2019/04/18 06:00
MHDA- 2020/10/21 06:00
PMCR- 2019/04/16
CRDT- 2019/04/18 06:00
PHST- 2018/12/17 00:00 [received]
PHST- 2019/03/25 00:00 [accepted]
PHST- 2019/04/18 06:00 [entrez]
PHST- 2019/04/18 06:00 [pubmed]
PHST- 2020/10/21 06:00 [medline]
PHST- 2019/04/16 00:00 [pmc-release]
AID - 10.1038/s41598-019-42127-8 [pii]
AID - 42127 [pii]
AID - 10.1038/s41598-019-42127-8 [doi]
PST - epublish
SO  - Sci Rep. 2019 Apr 16;9(1):6165. doi: 10.1038/s41598-019-42127-8.