PMID- 25994074
OWN - NLM
STAT- MEDLINE
DCOM- 20160413
LR  - 20220408
IS  - 1432-0428 (Electronic)
IS  - 0012-186X (Linking)
VI  - 58
IP  - 8
DP  - 2015 Aug
TI  - GIP increases adipose tissue expression and blood levels of MCP-1 in humans and 
      links high energy diets to inflammation: a randomised trial.
PG  - 1759-68
LID - 10.1007/s00125-015-3618-4 [doi]
AB  - AIMS/HYPOTHESIS: Obesity is associated with elevated monocyte chemoattractant 
      protein-1 (MCP-1), a proinflammatory chemokine related to diabetes and 
      cardiovascular disease. Since obesity is triggered by energy dense diets, we 
      hypothesised that nutrient induced intestinal hormones such as glucose-dependent 
      insulinotropic peptide (GIP) may directly stimulate the release of chemokines 
      from adipose tissue and induce low-grade inflammation. METHODS: GIP effects on 
      gene expression and secretion of inflammatory markers were studied by microarray 
      analysis and PCR from human subcutaneous fat biopsies of slightly obese but 
      healthy volunteers in the metabolic ward of German Institute of Human Nutrition, 
      Department of Clinical Nutrition, Potsdam-Rehbrucke. To allocate the participants 
      to the study arms they were numbered in order of their recruitment and then 
      assigned to the groups by a random number generator. In a randomised, 
      single-blind (participants) crossover design, the participants received GIP 
      infusions in postprandial concentrations (2 pmol kg(-1) min(-1)) or saline (154 
      mmol/l NaCl) infusions for 240 min either alone, in combination with 
      hyperinsulinaemic-euglycaemic (EU) or hyperinsulinaemic-hyperglycaemic (HC) 
      clamps. Possible mechanisms of GIP effects were investigated in single and 
      co-cultures of macrophage and adipocyte cell lines and in primary human 
      monocytes, macrophages and adipocytes. RESULTS: A total of 17 participants were 
      randomised to the following groups: EU with GIP infusion (n = 9); EU with NaCl 
      infusion (n = 9); HC with GIP infusion (n = 8); HC with NaCl infusion (n = 8); 
      sole GIP infusion (n = 11) and sole placebo infusion (n = 11). All 17 individuals 
      were analysed. The study is completed. In human subcutaneous adipose tissue 
      (hSCAT), infusions of GIP significantly increased inflammatory chemokine and 
      cytokine gene networks in transcriptomic microarray analyses. Particularly MCP-1 
      (180 +/- 26%), MCP-2 (246 +/- 58%) and IL-6 (234 +/- 40%) mRNA levels in adipose tissue 
      as well as circulating plasma concentrations of MCP-1 (165 +/- 12 vs 135 +/- 13 
      pg/ml; GIP vs saline after 240 min; p < 0.05 for all variables) in humans 
      increased independently of circulating insulin or glucose plasma concentrations. 
      GIP stimulation increased Mcp-1 mRNA-expression in co-cultures of differentiated 
      3T3L1-adipocytes and RAW 264.7 macrophages but not in the isolated cell lines. 
      Similarly, GIP increased MCP-1 transcripts in co-cultures of primary human 
      macrophages with human adipocytes. GIP receptor (GIPR) transcripts were present 
      in primary monocytes and the different cell lines and induced activation of 
      extracellular related kinase (ERK) as well as increases in cAMP, indicating 
      functional receptors. CONCLUSIONS/INTERPRETATION: Our findings suggest that the 
      nutrient induced gut hormone GIP may initiate adipose tissue inflammation by 
      triggering a crosstalk of adipocytes and macrophages involving MCP-1. TRIAL 
      REGISTRATION: ClinicalTrials.gov NCT00774488. FUNDING: This work was supported by 
      the German Research Foundation (DFG): grant No. Pf164/021002.
FAU - Gogebakan, Ozlem
AU  - Gogebakan O
AD  - Department of Clinical Nutrition, German Institute of Human Nutrition, 
      Potsdam-Rehbruecke, Arthur-Scheunert-Allee 155, 14558, Nuthetal, Germany.
FAU - Osterhoff, Martin A
AU  - Osterhoff MA
FAU - Schuler, Rita
AU  - Schuler R
FAU - Pivovarova, Olga
AU  - Pivovarova O
FAU - Kruse, Michael
AU  - Kruse M
FAU - Seltmann, Anne-Cathrin
AU  - Seltmann AC
FAU - Mosig, Alexander S
AU  - Mosig AS
FAU - Rudovich, Natalia
AU  - Rudovich N
FAU - Nauck, Michael
AU  - Nauck M
FAU - Pfeiffer, Andreas F H
AU  - Pfeiffer AF
LA  - eng
SI  - ClinicalTrials.gov/NCT00774488
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20150521
PL  - Germany
TA  - Diabetologia
JT  - Diabetologia
JID - 0006777
RN  - 0 (Chemokine CCL2)
RN  - 0 (Insulin)
RN  - 59392-49-3 (Gastric Inhibitory Polypeptide)
SB  - IM
MH  - Adipocytes/drug effects/metabolism
MH  - Adipose Tissue/*drug effects/metabolism
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Cells, Cultured
MH  - Chemokine CCL2/blood/genetics/*metabolism
MH  - Cross-Over Studies
MH  - *Diet
MH  - Gastric Inhibitory Polypeptide/blood/*pharmacology
MH  - Gene Expression/*drug effects
MH  - Humans
MH  - Inflammation/blood/*metabolism
MH  - Insulin/blood
MH  - Male
MH  - Middle Aged
MH  - Obesity/*metabolism
MH  - Signal Transduction/drug effects
MH  - Single-Blind Method
MH  - Young Adult
EDAT- 2015/05/23 06:00
MHDA- 2016/04/14 06:00
CRDT- 2015/05/22 06:00
PHST- 2015/02/19 00:00 [received]
PHST- 2015/04/15 00:00 [accepted]
PHST- 2015/05/22 06:00 [entrez]
PHST- 2015/05/23 06:00 [pubmed]
PHST- 2016/04/14 06:00 [medline]
AID - 10.1007/s00125-015-3618-4 [doi]
PST - ppublish
SO  - Diabetologia. 2015 Aug;58(8):1759-68. doi: 10.1007/s00125-015-3618-4. Epub 2015 
      May 21.