Elevated Expression of Osteopontin May Be Related to Adipose Tissue Macrophage Accumulation and Liver Steatosis in Morbid Obesity
- Adeline Bertola, PhD student1,2,
- Vanessa Deveaux, PhD student3,4,
- Stéphanie Bonnafous, Research assistant1,2,6,
- Déborah Rousseau, PhD1,2,
- Rodolphe Anty, MD, PhD1,2,6,
- Abdelilah Wakkach, PhD2,7,
- Moncef Dahman, MD6,
- Joan Tordjman, PhD8,
- Karine Clément, MD, PhD8,
- Siobhán E. McQuaid, MD9,
- Keith N. Frayn, PhD9,
- Pierre-Michel Huet, MD, PhD1,2,6,
- Jean Gugenheim, MD, PhD1,2,6,
- Sophie Lotersztajn, PhD3,4,5,
- Yannick Le Marchand-Brustel, PhD1,2,6,
- Albert Tran, MD, PhD1,2,6 and
- Philippe Gual, PhD (gual{at}unice.fr)1,2,6
- 1 INSERM, U895, Team 8 « Hepatic complications in obesity », Nice, France
- 2 University of Nice-Sophia-Antipolis, Faculty of Medicine, Nice, France
- 3 INSERM, U841, Créteil, France
- 4 University of Paris 12, Faculty of Medicine, Créteil, France
- 5 AP-HP, Henri Mondor-Albert Chenevier group, Hepatology and Gastroenterology department, Créteil, France
- 6 CHU of Nice, Digestive Center, Nice, France
- 7 CNRS, FRE2943, Nice, France
- 8 INSERM, U872, Cordelier Research Center, Team 7, Paris, France; Pierre et Marie-Curie-Paris 6, Paris, France
- 9 OCDEM, Churchill Hospital, Headington, UK
Abstract
Objective: Osteopontin plays an important role in the development of insulin-resistance and liver complications in dietary murine models. We aimed to determine the expression pattern of OPN and its receptor CD44 in obese patients and mice according to insulin-resistance and liver steatosis.
Research design and methods: Osteopontin and CD44 expressions were studied in 52 morbidly obese patients and in mice. Cellular studies were performed in HepG2 cells.
Results: Hepatic OPN and CD44 expressions were strongly correlated with liver steatosis and insulin-resistance in obese patients and mice. This increased OPN expression could be due to the accumulation of triglycerides since fat loading in HepG2 promotes OPN expression. In contrast, OPN expression in adipose tissue (AT) was enhanced independently of insulin-resistance and hepatic steatosis in obese patients. The elevated OPN expression in AT was paralleled with the AT macrophage infiltration, and both phenomena were reversed following weight loss. The circulating OPN level was slightly elevated in obese patients and was not related to liver steatosis. Further, AT did not appear to secrete OPN. In contrast, bariatric surgery-induced weight loss induced a strong increase in circulating OPN.
Conclusions: The modestly elevated circulating OPN levels in morbidly obese patients were not related to liver steatosis and did not appear to result from adipose tissue secretion. In subcutaneous AT, expression of OPN was directly related to macrophage accumulation independently from liver complications. In contrast, hepatic OPN and CD44 expressions were related to insulin-resistance and steatosis, suggesting their local implication in the progression of liver injury.
Footnotes
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- Received March 21, 2008.
- Accepted October 16, 2008.
- Copyright © American Diabetes Association
