title: Circulating glucagon is associated with inflammatory mediators in metabolically compromised subjects.
abstract: BACKGROUND
  Acute phase mediators promote metabolic changes by modifying circulating hormones. However, there is virtually no data about the link between glucagon and inflammatory parameters in obesity-related chronic low-grade inflammation.
  
  
  METHODS
  We performed both cross-sectional and longitudinal (diet-induced weight loss) studies.
  
  
  METHODS
  Circulating glucagon concentrations (ELISA), parameters of glucose and lipid metabolism, interleukin 6 (IL6), and complement factor B (CFB) were analyzed in 316 subjects (250 men and 66 women). The effects of weight loss were investigated in an independent cohort of 20 subjects.
  
  
  RESULTS
  Circulating glucagon significantly correlated with glucose (r=0.407, P<0.0001), HbAlc (r=0.426, P<0.0001), fasting triglycerides (r=0.356, P=0.001), and parameters of innate immune response system such as IL6 (r=0.342, P=0.050) and CFB (r=0.404, P=0.002) in obese subjects with altered glucose tolerance, but not in individuals with normal glucose tolerance (NGT). In obese and NGT subjects, glucagon was associated with fasting triglycerides (r=0.475, P=0.003) and CFB (r=0.624, P=0.001). In obese subjects, glucagon (P=0.019) and CFB (P=0.002) independently contributed to 26% of fasting triglyceride variance (P<0.0001) after controlling for the effects of age and fasting serum glucose concentration in multiple lineal regression models. Moreover, concomitant with fat mass, fasting triglycerides, and CFB, weight loss led to significantly decreased circulating glucagon (-23.1%, P=0.004).
  
  
  CONCLUSIONS
  According to the current results, acute phase reactants such as IL6 and CFB are associated with fasting glucagon in metabolically compromised subjects. This suggests that glucagon may be behind the association between inflammatory and metabolic parameters in obesity-associated chronic low-grade inflammation.
authors.affiliation: Service of Diabetes, Endocrinology and Nutrition (UDEN), Institut d'Investigació Biomédica de Girona (IdIBGi), Hospital of Girona Dr Josep Trueta, Girona, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Ortega
authors.forename: José M
authors.initials: JM
authors.lastname: Moreno-Navarrete
authors.forename: Mónica
authors.initials: M
authors.lastname: Sabater
authors.forename: Wifredo
authors.initials: W
authors.lastname: Ricart
authors.forename: Gema
authors.initials: G
authors.lastname: Frühbeck
authors.forename: José M
authors.initials: JM
authors.lastname: Fernández-Real
mesh_terms: D000328:Adult; D000368:Aged; D000886:Anthropometry; D015992:Body Mass Index; D015331:Cohort Studies; D011415:Complement Factor B / Q000032:analysis / Q000378:metabolism; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005934:Glucagon / Q000097:blood*; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000097:blood; D050356:Lipid Metabolism / Q000502:physiology; D008297:Male; D008659:Metabolic Diseases / Q000097:blood*; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000628:therapy; D014280:Triglycerides / Q000097:blood; D015431:Weight Loss / Q000502:physiology
chemical_list: D011415:Complement Factor B; D005934:Glucagon; D006442:Glycated Hemoglobin; D018836:Inflammation Mediators; D015850:Interleukin-6; D014280:Triglycerides