title: Obesity and low-grade inflammation increase plasma follistatin-like 3 in humans.
abstract: BACKGROUND
  Rodent models suggest that follistatin-like 3 (fstl3) is associated with diabetes and obesity. In humans, plasma fstl3 is reduced with gestational diabetes. In vitro, TNF-α induces fstl3 secretion, which suggests a link to inflammation.
  
  
  OBJECTIVE
  To elucidate the association between plasma fstl3 and obesity, insulin resistance, and low-grade inflammation in humans.
  
  
  METHODS
  Plasma fstl3 levels were determined in a cross-sectional study including three groups: patients with type 2 diabetes, impaired glucose tolerance, and healthy controls. In addition, lipopolysaccharide (LPS), TNF-α, or interleukin-6 (IL-6) as well as a hyperinsulinemic euglycemic clamp were used to examine if plasma fstl3 was acutely regulated in humans.
  
  
  RESULTS
  Plasma fstl3 was increased in obese subjects independent of glycemic state. Moreover, plasma fstl3 was positively correlated with fat mass, plasma leptin, fasting insulin, and HOMA B and negatively with HOMA S. Furthermore plasma fstl3 correlated positively with plasma TNF-α and IL-6 levels. Infusion of LPS and TNF-α, but not IL-6 and insulin, increased plasma fstl3 in humans.
  
  
  CONCLUSIONS
  Plasma fstl3 is increased in obese subjects and associated with fat mass and low-grade inflammation. Furthermore, TNF-α increased plasma fstl3, suggesting that TNF-α is one of the inflammatory drivers of increased systemic levels of fstl3.
authors.affiliation: Centre of Inflammation and Metabolism (CIM), The Centre for Physical Activity Research (CFAS), Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark.
authors.forename: Claus
authors.identifier: 0000-0003-4063-115X
authors.initials: C
authors.lastname: Brandt
authors.affiliation: Centre of Inflammation and Metabolism (CIM), The Centre for Physical Activity Research (CFAS), Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark.
authors.forename: Maria
authors.initials: M
authors.lastname: Pedersen
authors.affiliation: Centre of Inflammation and Metabolism (CIM), The Centre for Physical Activity Research (CFAS), Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Rinnov
authors.affiliation: Centre of Inflammation and Metabolism (CIM), The Centre for Physical Activity Research (CFAS), Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark.
authors.forename: Anne S
authors.initials: AS
authors.lastname: Andreasen
authors.affiliation: Centre of Inflammation and Metabolism (CIM), The Centre for Physical Activity Research (CFAS), Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark ; Neurointensive Care Unit, Department of Neuroanaesthesiology, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Møller
authors.affiliation: Centre of Inflammation and Metabolism (CIM), The Centre for Physical Activity Research (CFAS), Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark.
authors.forename: Pernille
authors.identifier: 0000-0003-1206-8574
authors.initials: P
authors.lastname: Hojman
authors.affiliation: Centre of Inflammation and Metabolism (CIM), The Centre for Physical Activity Research (CFAS), Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark.
authors.forename: Bente K
authors.initials: BK
authors.lastname: Pedersen
authors.affiliation: Centre of Inflammation and Metabolism (CIM), The Centre for Physical Activity Research (CFAS), Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark ; Department of Clinical Biochemistry, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
authors.forename: Peter
authors.identifier: 0000-0002-2404-2702
authors.initials: P
authors.lastname: Plomgaard
mesh_terms: D052242:Adiponectin / Q000378:metabolism; D000328:Adult; D003430:Cross-Sectional Studies; D038702:Follistatin-Related Proteins / Q000097:blood* / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009765:Obesity / Q000097:blood* / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D052242:Adiponectin; D038702:Follistatin-Related Proteins; D007328:Insulin; D015850:Interleukin-6; D020738:Leptin; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha
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