title: Obesity-associated hepatosteatosis and impairment of glucose homeostasis are attenuated by haptoglobin deficiency.
abstract: OBJECTIVE
  Haptoglobin (Hp) is upregulated in both inflammation and obesity. The low chronic inflammatory state, caused by massive adipose tissue macrophage (ATM) infiltration found in obesity, and low adiponectin have been implicated in the development of insulin resistance and hepatosteatosis. The aim of this work was to investigate whether and how Hp interferes with the onset of obesity-associated complications.
  
  
  METHODS
  Hp-null (Hp(-/-)) and wild-type (WT) mice were metabolically profiled under chow-food diet (CFD) and high-fat diet (HFD) feeding by assessing physical parameters, glucose tolerance, insulin sensitivity, insulin response to glucose load, liver triglyceride content, plasma levels of leptin, insulin, glucose, and adiponectin. ATM content was evaluated by using immunohistochemistry (anti-F4/80 antibody). Adiponectin expression was measured in Hp-treated, cultured 3T3-L1 and human adipocytes.
  
  
  RESULTS
  No genotype-related difference was found in CFD animals. HFD-Hp(-/-) mice revealed significantly higher glucose tolerance, insulin sensitivity, glucose-stimulated insulin secretion, and adiponectin expression and reduced hepatomegaly/steatosis compared with HFD-WT mice. White adipose tissue (WAT) of HFD-Hp(-/-) mice showed higher activation of insulin signaling cascade, lower ATM, and higher adiponectin expression. Hp was able to inhibit adiponectin expression in cultured adipocytes.
  
  
  CONCLUSIONS
  We demonstrated that in the absence of Hp, obesity-associated insulin resistance and hepatosteatosis are attenuated, which is associated with reduced ATM content, increased plasma adiponectin, and higher WAT insulin sensitivity.
authors.affiliation: Dulbecco Telethon Institute, Rome, Italy.
authors.forename: Simonetta
authors.initials: S
authors.lastname: Lisi
authors.forename: Olimpia
authors.initials: O
authors.lastname: Gamucci
authors.forename: Teresa
authors.initials: T
authors.lastname: Vottari
authors.forename: Gaia
authors.initials: G
authors.lastname: Scabia
authors.forename: Marcella
authors.initials: M
authors.lastname: Funicello
authors.forename: Matilde
authors.initials: M
authors.lastname: Marchi
authors.forename: Giulia
authors.initials: G
authors.lastname: Galli
authors.forename: Ivan
authors.initials: I
authors.lastname: Arisi
authors.forename: Rossella
authors.initials: R
authors.lastname: Brandi
authors.forename: Mara
authors.initials: M
authors.lastname: D'Onofrio
authors.forename: Aldo
authors.initials: A
authors.lastname: Pinchera
authors.forename: Ferruccio
authors.initials: F
authors.lastname: Santini
authors.forename: Margherita
authors.initials: M
authors.lastname: Maffei
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D005234:Fatty Liver / Q000209:etiology* / Q000378:metabolism; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D006242:Haptoglobins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000150:complications*
chemical_list: D001786:Blood Glucose; D006242:Haptoglobins; D005947:Glucose