Obesity-Associated Hepatosteatosis and Impairment of Glucose Homeostasis Are Attenuated by Haptoglobin Deficiency
- Simonetta Lisi1,2,
- Olimpia Gamucci2,
- Teresa Vottari1,2,
- Gaia Scabia1,2,
- Marcella Funicello1,2,
- Matilde Marchi1,2,
- Giulia Galli2,
- Ivan Arisi3,
- Rossella Brandi3,
- Mara D’Onofrio3,
- Aldo Pinchera2,
- Ferruccio Santini2 and
- Margherita Maffei1,2⇓
- 1Dulbecco Telethon Institute, Rome, Italy.
- 2Department of Endocrinology and Kidney, University-Hospital of Pisa, Pisa, Italy.
- 3European Brain Research Institute, Rome, Italy.
- Corresponding author: Margherita Maffei, , or Ferruccio Santini, .
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.
RESEARCH DESIGN AND 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.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db10-1536/-/DC1.
- Received November 4, 2010.
- Accepted July 13, 2011.
- © 2011 by the American Diabetes Association.
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