title: Adipokine and insulin profiles distinguish diabetogenic and non-diabetogenic obesities in mice.
abstract: OBJECTIVE
  To use longitudinal profiling of plasma adipokines to distinguish diabetogenic vs. non-diabetogenic obesity syndrome in two new mouse models of polygenic obesity.
  
  
  METHODS
  Male mice of the NONcNZO5 strain develop a polygenic obesity syndrome uncomplicated by diabetes, whereas NONcNZO10 males develop a comparable polygenic obesity that precipitates type 2 diabetes. A multiplex immunoassay for simultaneous measurement of insulin and a panel of mouse adipokines (leptin, resistin, adiponectin, interleukin-6, tumor necrosis factor alpha, macrophage chemoattractant protein-1, plasminogen activator inhibitor-1) were used to profile longitudinal changes in these strains between 4 and 16 weeks of age that might distinguish the non-diabetogenic vs. diabetogenic obesity (diabesity).
  
  
  RESULTS
  Both strains became adipose, with NONcNZO5 males attaining a higher mean body weight with a higher percentage fat content. Weight gain in NONcNZO5 was accompanied by a transient peak in plasma insulin (PI) at 8 weeks followed by a decline into normal range, with normoglycemia maintained throughout. In contrast, NONcNZO10 showed no early PI secretory response because both body weight and plasma glucose increased between 4 and 8 weeks. Only after 12 weeks, with hyperglycemia established, was a delayed PI secretory response observed. Neither plasma leptin nor adiponectin concentrations significantly differentiated the two syndromes over time. However, repeated measures ANOVA showed that NONcNZO10 males maintained significantly higher plasma concentrations of two adipokines, resistin and plasminogen activator inhibitor-1, and the pro-inflammatory cytokine/adipokine macrophage chemoattractant protein-1.
  
  
  CONCLUSIONS
  Longitudinal profiling of PI and adipokines in two new mouse models developing moderate obesity demonstrated that specific marker signatures differentiated a non-diabetogenic obesity from a diabetogenic obesity.
authors: The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA. ehl@jax.org
authors: Edward H
authors: EH
authors: Leiter
authors: Peter C
authors: PC
authors: Reifsnyder
authors: Qiang
authors: Q
authors: Xiao
authors: Jehangir
authors: J
authors: Mistry
mesh_terms: D052242:Adiponectin / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D018932:Chemokine CCL2 / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000235:genetics; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008137:Longitudinal Studies; D008297:Male; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000097:blood* / Q000235:genetics; D036361:Peptide Hormones / Q000097:blood*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D052243:Resistin / Q000097:blood
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D007328:Insulin; D020738:Leptin; D036361:Peptide Hormones; D017395:Plasminogen Activator Inhibitor 1; D052243:Resistin