PMID- 25537494
OWN - NLM
STAT- MEDLINE
DCOM- 20150501
LR  - 20220409
IS  - 1522-1555 (Electronic)
IS  - 0193-1849 (Linking)
VI  - 308
IP  - 5
DP  - 2015 Mar 1
TI  - Increased GIP signaling induces adipose inflammation via a HIF-1alpha-dependent 
      pathway and impairs insulin sensitivity in mice.
PG  - E414-25
LID - 10.1152/ajpendo.00418.2014 [doi]
AB  - Glucose-dependent insulinotropic polypeptide (GIP) is a gut hormone secreted in 
      response to dietary fat and glucose. The blood GIP level is elevated in obesity 
      and diabetes. GIP stimulates proinflammatory gene expression and impairs insulin 
      sensitivity in cultured adipocytes. In obesity, hypoxia within adipose tissue can 
      induce inflammation. The aims of this study were 1) to examine the 
      proinflammatory effect of increased GIP signaling in adipose tissues in vivo and 
      2) to clarify the association between GIP and hypoxic signaling in adipose tissue 
      inflammation. We administered GIP intraperitoneally to misty (lean) and db/db 
      (obese) mice and examined adipose tissue inflammation and insulin sensitivity. We 
      also examined the effects of GIP and hypoxia on expression of the GIP receptor 
      (GIPR) gene and proinflammatory genes in 3T3-L1 adipocytes. GIP administration 
      increased monocyte chemoattractant protein-1 (MCP-1) expression and macrophage 
      infiltration into adipose tissue and increased blood glucose in db/db mice. GIPR 
      and hypoxia-inducible factor-1alpha (HIF-1alpha) expressions were positively correlated 
      in the adipose tissue in mice. GIPR expression increased dramatically in 
      differentiated adipocytes. GIP treatment of adipocytes increased MCP-1 and 
      interleukin-6 (IL-6) production. Adipocytes cultured either with RAW 264 
      macrophages or under hypoxia expressed more GIPR and HIF-1alpha, and GIP treatment 
      increased gene expression of plasminogen activator inhibitor 1 and IL-6. HIF-1alpha 
      gene silencing diminished both macrophage- and hypoxia-induced GIPR expression 
      and GIP-induced IL-6 expression in adipocytes. Thus, increased GIP signaling 
      plays a significant role in adipose tissue inflammation and thereby insulin 
      resistance in obese mice, and HIF-1alpha may contribute to this process.
CI  - Copyright (c) 2015 the American Physiological Society.
FAU - Chen, Shu
AU  - Chen S
AD  - Biological Science Laboratories, Kao Corporation, Tochigi, Japan.
FAU - Okahara, Fumiaki
AU  - Okahara F
AD  - Biological Science Laboratories, Kao Corporation, Tochigi, Japan.
FAU - Osaki, Noriko
AU  - Osaki N
AD  - Biological Science Laboratories, Kao Corporation, Tochigi, Japan.
FAU - Shimotoyodome, Akira
AU  - Shimotoyodome A
AD  - Biological Science Laboratories, Kao Corporation, Tochigi, Japan 
      shimotoyodome.akira@kao.co.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141223
PL  - United States
TA  - Am J Physiol Endocrinol Metab
JT  - American journal of physiology. Endocrinology and metabolism
JID - 100901226
RN  - 0 (Hif1a protein, mouse)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 59392-49-3 (Gastric Inhibitory Polypeptide)
SB  - IM
MH  - 3T3-L1 Cells
MH  - Adipose Tissue/drug effects/*metabolism/pathology
MH  - Animals
MH  - Cells, Cultured
MH  - Gastric Inhibitory Polypeptide/*metabolism/pharmacology
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*physiology
MH  - Inflammation/*metabolism/pathology
MH  - *Insulin Resistance
MH  - Macrophages, Peritoneal/metabolism/pathology
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Obesity/metabolism/pathology
MH  - Signal Transduction/drug effects/physiology
MH  - Up-Regulation
OTO - NOTNLM
OT  - GIP
OT  - adipose tissue inflammation
OT  - hypoxia
OT  - insulin resistance
OT  - macrophage
EDAT- 2014/12/30 06:00
MHDA- 2015/05/02 06:00
CRDT- 2014/12/25 06:00
PHST- 2014/12/25 06:00 [entrez]
PHST- 2014/12/30 06:00 [pubmed]
PHST- 2015/05/02 06:00 [medline]
AID - ajpendo.00418.2014 [pii]
AID - 10.1152/ajpendo.00418.2014 [doi]
PST - ppublish
SO  - Am J Physiol Endocrinol Metab. 2015 Mar 1;308(5):E414-25. doi: 
      10.1152/ajpendo.00418.2014. Epub 2014 Dec 23.