PMID- 22851489
OWN - NLM
STAT- MEDLINE
DCOM- 20121218
LR  - 20211021
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 97
IP  - 10
DP  - 2012 Oct
TI  - Increased tenascin C and Toll-like receptor 4 levels in visceral adipose tissue 
      as a link between inflammation and extracellular matrix remodeling in obesity.
PG  - E1880-9
LID - 10.1210/jc.2012-1670 [doi]
AB  - CONTEXT: Obesity is associated with an altered inflammatory and extracellular 
      matrix (ECM) profile. Tenascin C (TNC) is an ECM glycoprotein with 
      proinflammatory effects. OBJECTIVE: We aimed to explore the expression levels of 
      TNC in adipose tissue analyzing the contribution of adipocytes and stromovascular 
      fraction cells (SVFC) as well as its impact on inflammation and ECM regulation. 
      We also analyzed the effect of the stimulation with TNF-alpha and lipopolysaccharide 
      (LPS) on both SVFC and adipocytes. PATIENTS AND METHODS: Samples obtained from 75 
      subjects were used in the study. Expression levels of TNC, TLR4, MMP2, and MMP9 
      were analyzed in visceral adipose tissue (VAT) as well as in both adipocytes and 
      SVFC. In addition, Tnc expression was measured in two mice models of obesity. 
      RESULTS: We show, for the first time, that VAT expression levels of TNC are 
      increased in normoglycemic and type 2 diabetic obese patients (P<0.01) as well as 
      in obese patients with nonalcoholic steatohepatitis (P<0.01). Furthermore, 
      expression levels of Tnc in epididymal adipose tissue from two different mice 
      models of obesity were significantly increased (P<0.01). TNC and TLR4 were mainly 
      expressed by SVFC, and its expression was significantly enhanced (P<0.01) by 
      TNF-alpha treatment. LPS treatment also increased mRNA levels of TNC. Moreover, the 
      addition of exogenous TNC induced (P<0.05) TLR4 and CCL2 mRNA expression in human 
      adipocyte cultures. CONCLUSIONS: These findings indicate that TNC is involved in 
      the etiopathology of obesity via visceral adipose tissue inflammation 
      representing a link with ECM remodeling.
FAU - Catalan, Victoria
AU  - Catalan V
AD  - Metabolic Research Laboratory, Department of Surgery, Clinica Universidad de 
      Navarra, Avenuda Pio XII, 36, 31008 Pamplona, Spain.
FAU - Gomez-Ambrosi, Javier
AU  - Gomez-Ambrosi J
FAU - Rodriguez, Amaia
AU  - Rodriguez A
FAU - Ramirez, Beatriz
AU  - Ramirez B
FAU - Rotellar, Fernando
AU  - Rotellar F
FAU - Valenti, Victor
AU  - Valenti V
FAU - Silva, Camilo
AU  - Silva C
FAU - Gil, Maria J
AU  - Gil MJ
FAU - Salvador, Javier
AU  - Salvador J
FAU - Fruhbeck, Gema
AU  - Fruhbeck G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120731
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Lipopolysaccharides)
RN  - 0 (TLR4 protein, human)
RN  - 0 (Tenascin)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Adipocytes/immunology/metabolism
MH  - Adult
MH  - Animals
MH  - Diabetes Mellitus, Type 2/immunology/metabolism
MH  - Disease Models, Animal
MH  - Extracellular Matrix/immunology/metabolism
MH  - Fatty Liver/immunology/metabolism
MH  - Female
MH  - Humans
MH  - Inflammation/immunology/*metabolism
MH  - Intra-Abdominal Fat/drug effects/immunology/*metabolism
MH  - Lipopolysaccharides/pharmacology
MH  - Macrophages, Peritoneal/immunology/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Obese
MH  - Middle Aged
MH  - Non-alcoholic Fatty Liver Disease
MH  - Obesity/immunology/*metabolism
MH  - Tenascin/genetics/*metabolism
MH  - Toll-Like Receptor 4/genetics/*metabolism
MH  - Tumor Necrosis Factor-alpha/pharmacology
MH  - Young Adult
PMC - PMC3462948
EDAT- 2012/08/02 06:00
MHDA- 2012/12/19 06:00
PMCR- 2013/10/01
CRDT- 2012/08/02 06:00
PHST- 2012/08/02 06:00 [entrez]
PHST- 2012/08/02 06:00 [pubmed]
PHST- 2012/12/19 06:00 [medline]
PHST- 2013/10/01 00:00 [pmc-release]
AID - jc.2012-1670 [pii]
AID - 12-1670 [pii]
AID - 10.1210/jc.2012-1670 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2012 Oct;97(10):E1880-9. doi: 10.1210/jc.2012-1670. Epub 
      2012 Jul 31.