PMID- 23104131
OWN - NLM
STAT- MEDLINE
DCOM- 20130403
LR  - 20211021
IS  - 1546-170X (Electronic)
IS  - 1078-8956 (Print)
IS  - 1078-8956 (Linking)
VI  - 18
IP  - 11
DP  - 2012 Nov
TI  - Immunomodulatory glycan LNFPIII alleviates hepatosteatosis and insulin resistance 
      through direct and indirect control of metabolic pathways.
PG  - 1665-72
LID - 10.1038/nm.2962 [doi]
AB  - Parasitic worms express host-like glycans to attenuate the immune response of 
      human hosts. The therapeutic potential of this immunomodulatory mechanism in 
      controlling the metabolic dysfunction that is associated with chronic 
      inflammation remains unexplored. We demonstrate here that administration of 
      lacto-N-fucopentaose III (LNFPIII), a Lewis(X)-containing immunomodulatory glycan 
      found in human milk and on parasitic helminths, improves glucose tolerance and 
      insulin sensitivity in diet-induced obese mice. This effect is mediated partly 
      through increased interleukin-10 (Il-10) production by LNFPIII-activated 
      macrophages and dendritic cells, which reduces white adipose tissue inflammation 
      and sensitizes the insulin response of adipocytes. Concurrently, LNFPIII 
      treatment upregulates nuclear receptor subfamily 1, group H, member 4 (Fxr-alpha, 
      also known as Nr1h4) to suppress lipogenesis in the liver, conferring protection 
      against hepatosteatosis. At the signaling level, the extracellular 
      signal-regulated kinase (Erk)-activator protein 1 (Ap1) pathway seems to mediate 
      the effects of LNFPIII on both inflammatory and metabolic pathways. Our results 
      suggest that LNFPIII may provide new therapeutic approaches to treat metabolic 
      diseases.
FAU - Bhargava, Prerna
AU  - Bhargava P
AD  - Department of Genetics and Complex Diseases, Division of Biological Sciences, 
      Harvard School of Public Health, Boston, MA, USA.
FAU - Li, Changlin
AU  - Li C
FAU - Stanya, Kristopher J
AU  - Stanya KJ
FAU - Jacobi, David
AU  - Jacobi D
FAU - Dai, Lingling
AU  - Dai L
FAU - Liu, Sihao
AU  - Liu S
FAU - Gangl, Matthew R
AU  - Gangl MR
FAU - Harn, Donald A
AU  - Harn DA
FAU - Lee, Chih-Hao
AU  - Lee CH
LA  - eng
GR  - R01 DK075046/DK/NIDDK NIH HHS/United States
GR  - T32 ES016645/ES/NIEHS NIH HHS/United States
GR  - R01DK075046/DK/NIDDK NIH HHS/United States
GR  - R01AI056484/AI/NIAID NIH HHS/United States
GR  - T32ES016645/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20121028
PL  - United States
TA  - Nat Med
JT  - Nature medicine
JID - 9502015
RN  - 0 (Amino Sugars)
RN  - 0 (Polysaccharides)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (lacto-N-fucopentaose III)
RN  - 0C5V0MRU6P (farnesoid X-activated receptor)
RN  - 130068-27-8 (Interleukin-10)
SB  - IM
MH  - *Adipose Tissue/growth & development/pathology
MH  - *Amino Sugars/administration & dosage/immunology/metabolism
MH  - Animals
MH  - Dendritic Cells/metabolism
MH  - Diabetes Mellitus, Experimental/pathology/therapy
MH  - Diet, High-Fat
MH  - Fatty Liver/immunology/metabolism/therapy
MH  - Hep G2 Cells
MH  - Humans
MH  - *Inflammation/immunology/pathology/therapy
MH  - Insulin Resistance/immunology
MH  - Interleukin-10/metabolism
MH  - Liver/metabolism/pathology
MH  - Macrophages/metabolism
MH  - *Metabolic Networks and Pathways/immunology
MH  - Mice
MH  - Mice, Obese/immunology/metabolism
MH  - *Polysaccharides/administration & dosage/immunology/metabolism
MH  - *Receptors, Cytoplasmic and Nuclear/immunology/metabolism
MH  - Signal Transduction
PMC - PMC3493877
MID - NIHMS404535
COIS- COMPETING FINANCIAL INTERESTS The authors declare no competing financial 
      interests.
EDAT- 2012/10/30 06:00
MHDA- 2013/04/04 06:00
PMCR- 2013/05/01
CRDT- 2012/10/30 06:00
PHST- 2012/05/29 00:00 [received]
PHST- 2012/08/30 00:00 [accepted]
PHST- 2012/10/30 06:00 [entrez]
PHST- 2012/10/30 06:00 [pubmed]
PHST- 2013/04/04 06:00 [medline]
PHST- 2013/05/01 00:00 [pmc-release]
AID - nm.2962 [pii]
AID - 10.1038/nm.2962 [doi]
PST - ppublish
SO  - Nat Med. 2012 Nov;18(11):1665-72. doi: 10.1038/nm.2962. Epub 2012 Oct 28.