PMID- 29415997
OWN - NLM
STAT- MEDLINE
DCOM- 20191125
LR  - 20191125
IS  - 2041-4889 (Electronic)
VI  - 9
IP  - 2
DP  - 2018 Feb 7
TI  - Downregulation of beta1,4-galactosyltransferase 5 improves insulin resistance by 
      promoting adipocyte commitment and reducing inflammation.
PG  - 196
LID - 10.1038/s41419-017-0239-5 [doi]
LID - 196
AB  - Protein glycosylation is an important post-translational modification. Aberrant 
      glycosylation has been implicated in many diseases because of associated changes 
      in protein distribution and biological function. We showed that the expression of 
      beta1, 4-galactosyltransferase 5 (B4GalT5) was positively correlated with diabetes 
      and obesity. In vivo, B4GalT5 knockdown in subcutaneous adipose tissue alleviated 
      insulin resistance and adipose tissue inflammation, and increased adipogenesis in 
      high-fat diet (HFD)-fed mice and ob/ob mice. Downregulation of B4GalT5 in 
      preadipocyte cells induced commitment to the adipocyte lineage in the absence of 
      bone morphogenetic protein (BMP) 2/4 treatment, which is typically essential for 
      adipogenic commitment. RNAi silencing experiments showed B4GalT5 knockdown 
      activated Smad and p38 MPAK signaling pathways through both type 1A and 2 BMP 
      receptors. Remarkably, B4GalT5 knockdown decreased BMPRIA glycosylation but 
      increased BMPRIA stability and cellular location, thus leading to redistribution 
      of BMPRIA and activation of the BMP signaling pathway. Meanwhile, downregulation 
      of B4GalT5 decreased the infiltration of macrophages and the markers of M1 
      macrophages in subcutaneous adipose tissue of HFD mice and ob/ob mice. In bone 
      marrow-derived macrophages (BMDMs) and RAW264.7cells, B4GalT5 knockdown also 
      repressed the markers of M1 by reducing NFkappaB and JNK signaling. These results 
      demonstrated B4GalT5 downregulation improved insulin resistance by promoting 
      adipogenic commitment and decreasing M1 macrophage infiltration.
FAU - Li, Shu-Fen
AU  - Li SF
AD  - Key Laboratory of Metabolic Molecular Medicine, the Ministry of Education, 
      Department of Biochemistry and Molecular Biology, School of Basic Medical 
      Sciences, Fudan University Shanghai Medical College, Shanghai, 200032, China.
AD  - State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, 
      Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 
      200025, China.
FAU - Zhu, Cui-Song
AU  - Zhu CS
AD  - Key Laboratory of Metabolic Molecular Medicine, the Ministry of Education, 
      Department of Biochemistry and Molecular Biology, School of Basic Medical 
      Sciences, Fudan University Shanghai Medical College, Shanghai, 200032, China.
FAU - Wang, Yu-Meng
AU  - Wang YM
AD  - Biology Science Institutes, Chongqing Medical University, Chongqing, 400032, 
      China.
FAU - Xie, Xin-Xin
AU  - Xie XX
AD  - Biology Science Institutes, Chongqing Medical University, Chongqing, 400032, 
      China.
FAU - Xiao, Liu-Ling
AU  - Xiao LL
AD  - Key Laboratory of Metabolic Molecular Medicine, the Ministry of Education, 
      Department of Biochemistry and Molecular Biology, School of Basic Medical 
      Sciences, Fudan University Shanghai Medical College, Shanghai, 200032, China.
FAU - Zhang, Zhi-Chun
AU  - Zhang ZC
AD  - Biology Science Institutes, Chongqing Medical University, Chongqing, 400032, 
      China.
FAU - Tang, Qi-Qun
AU  - Tang QQ
AD  - Key Laboratory of Metabolic Molecular Medicine, the Ministry of Education, 
      Department of Biochemistry and Molecular Biology, School of Basic Medical 
      Sciences, Fudan University Shanghai Medical College, Shanghai, 200032, China.
FAU - Li, Xi
AU  - Li X
AUID- ORCID: 0000-0002-2716-7308
AD  - Key Laboratory of Metabolic Molecular Medicine, the Ministry of Education, 
      Department of Biochemistry and Molecular Biology, School of Basic Medical 
      Sciences, Fudan University Shanghai Medical College, Shanghai, 200032, China. 
      lixi@shmu.edu.cn.
AD  - Biology Science Institutes, Chongqing Medical University, Chongqing, 400032, 
      China. lixi@shmu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180207
PL  - England
TA  - Cell Death Dis
JT  - Cell death & disease
JID - 101524092
RN  - EC 2.4.1.- (Galactosyltransferases)
SB  - IM
MH  - Adipocytes/*metabolism
MH  - Animals
MH  - Down-Regulation
MH  - Galactosyltransferases/*metabolism
MH  - Humans
MH  - Inflammation/*genetics/*metabolism
MH  - Insulin Resistance/*genetics
MH  - Male
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Mice, Inbred C57BL
PMC - PMC5833706
COIS- The authors declare that they have no conflict of interest.
EDAT- 2018/02/09 06:00
MHDA- 2019/11/26 06:00
PMCR- 2018/02/07
CRDT- 2018/02/09 06:00
PHST- 2017/11/02 00:00 [received]
PHST- 2017/12/14 00:00 [accepted]
PHST- 2017/12/13 00:00 [revised]
PHST- 2018/02/09 06:00 [entrez]
PHST- 2018/02/09 06:00 [pubmed]
PHST- 2019/11/26 06:00 [medline]
PHST- 2018/02/07 00:00 [pmc-release]
AID - 10.1038/s41419-017-0239-5 [pii]
AID - 239 [pii]
AID - 10.1038/s41419-017-0239-5 [doi]
PST - epublish
SO  - Cell Death Dis. 2018 Feb 7;9(2):196. doi: 10.1038/s41419-017-0239-5.