Elevated Expression of Osteopontin May Be Related to Adipose Tissue Macrophage Accumulation and Liver Steatosis in Morbid Obesity

• DOI: 10.2337/db08-0400
• Publication Date: 2008-10-25T00:55:15Z
• Authors: Adeline Bertola; Vanessa Deveaux; Stéphanie Bonnafous; Déborah Rousseau; Rodolphe Anty; Abdelilah Wakkach; Moncef Dahman; Joan Tordjman; Karine Clément; Siobhán E. McQuaid; Keith N. Frayn; Pierre-Michel Huet; Jean Gugenheim; Sophie Lotersztajn; Yannick Le Marcha...; Albert Tran; Philippe Gual
• Keywords: Male; 0301 basic medicine; MESH: Osteopontin; Messenger; Gene Expression; Inbred C57BL; Mice; MESH: Reverse Transcriptase Polymerase Chain Reaction; MESH: Animals; CD44; Morbid; MESH: Fatty Liver; 2. Zero hunger; MESH: Middle Aged; Tumor; MESH: Immunoblotting; Reverse Transcriptase Polymerase Chain Reaction; Middle Aged; Obesity, Morbid; 3. Good health; [SDV] Life Sciences [q-bio]; Hyaluronan Receptors; Adipose Tissue; Liver; MESH: Antigens; Female; MESH: Adipose Tissue; Obesity Studies; Adult; MESH: Cell Line, Tumor; MESH: Gene Expression; Immunoblotting; 610; MESH: Antigens, CD44; Cell Line; MESH: Weight Loss; 03 medical and health sciences; MESH: RNA; MESH: Mice, Inbred C57BL; Cell Line, Tumor; 616; Weight Loss; [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology; Animals; Humans; [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology; Obesity; RNA, Messenger; Antigens; MESH: Mice; MESH: RNA, Messenger; MESH: Humans; Tumor Necrosis Factor-alpha; Macrophages; MESH: Oleic Acid; MESH: Macrophages; MESH: Adult; MESH: Obesity, Morbid; MESH: Male; MESH: Cell Line; Fatty Liver; Mice, Inbred C57BL; MESH: Tumor Necrosis Factor-alpha; RNA; Osteopontin; MESH: Female; MESH: Liver; Oleic Acid

OBJECTIVE—Osteopontin (OPN) 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—OPN 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 after 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.