Plasma Osteopontin Increases After Bariatric Surgery and Correlates with Markers of Bone Turnover But Not with Insulin Resistance

Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, Vienna, Austria.
Journal of Clinical Endocrinology &amp Metabolism (Impact Factor: 6.21). 06/2008; 93(6):2307-12. DOI: 10.1210/jc.2007-2383
Source: PubMed


Osteopontin (OPN) is a multifunctional protein involved in bone metabolism, cardiovascular disease, diabetes, and obesity. OPN levels are elevated in the plasma and adipose tissue of obese subjects, and are decreased with diet-induced weight loss.
We investigated the effect of bariatric surgery on plasma OPN concentrations in morbidly obese patients.
The study was performed at a university hospital.
We investigated 40 obese patients aged 43.1 +/- 1.8 yr, scheduled to undergo bariatric surgery. Roux-en-Y gastric bypass (RYGB) was performed in 30 subjects (27 females, three males), and laparoscopic adjustable gastric banding (LAGB) in 10 subjects (eight females, two males).
All patients were studied before and 1 yr (10.3-14.8 months) after the intervention.
OPN, leptin, C-reactive protein, insulin, the homeostatic model assessment insulin resistance index, calcium, 25-hydroxyvitamin D, C telopeptide, and osteocalcin were determined.
Both bariatric procedures significantly reduced body weight, body mass index, insulin, leptin, and C-reactive protein 1 yr after surgery. Plasma OPN increased from 31.4 +/- 3.8 to 52.8 +/- 3.7 ng/ml after RYGB (P < 0.001) and from 29.8 +/- 6.9 to 46.4 +/- 10.6 ng/ml after LAGB (P = 0.042). Preoperative OPN correlated with age, insulin, the homeostatic model assessment insulin resistance index, and postoperative OPN. Postoperative OPN correlated with C telopeptide and osteocalcin.
One year after RYGB and LAGB, plasma OPN levels significantly increased and correlated with biomarkers of bone turnover. Unlike other proinflammatory cytokines, OPN does not normalize but increases further after bariatric surgery.

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    • "Subjects who previously underwent gastric banding or Roux-en Y gastric bypass exhibited decreased body weight, body mass index, inflammation markers as well as reduced insulin resistance. However, all studies consistently reported a gradual increase of OPN blood concentrations after bariatric surgery [97–100]. Further investigations are needed to differentiate whether these changes are secondary to alterations of bone metabolism or an adaption to weight loss. "
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    ABSTRACT: Since its first description more than 20 years ago osteopontin has emerged as an active player in many physiological and pathological processes, including biomineralization, tissue remodeling and inflammation. As an extracellular matrix protein and proinflammatory cytokine osteopontin is thought to facilitate the recruitment of monocytes/macrophages and to mediate cytokine secretion in leukocytes. Modulation of immune cell response by osteopontin has been associated with various inflammatory diseases and may play a pivotal role in the development of adipose tissue inflammation and insulin resistance. Here we summarize recent findings on the role of osteopontin in metabolic disorders, particularly focusing on diabetes and obesity.
    Molecular Metabolism 07/2014; 3(4). DOI:10.1016/j.molmet.2014.03.004
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    ABSTRACT: Osteopontin (OPN) is a multifunctional matrix glycoprotein associated with bone metabolism and has been linked to chronic inflammation, insulin resistance, and atherosclerosis. Diet-induced weight loss decreases elevated OPN concentrations in obese patients. The aim of the current study was to investigate the role of OPN after bariatric surgery, where not only improvements of chronic inflammation, insulin resistance and comorbidities, but also malabsorption and altered bone metabolism have been reported. OPN plasma concentrations were determined in 31 morbidly obese patients (5 men, 26 women, BMI 46.2+/-7.1 kg/m2, age 41+/-11 years; mean+/-SD) before and 18 months after bariatric surgery, together with parameters of bone metabolism and inflammation. OPN concentrations increased by +20.3+/-26.6 ng/ml (mean+/-SD, p<0.01), concomitant to a weight loss of -38+/-22 kg, and a decrease in BMI by -13.1+/-7.7 kg/m2 (both p<0.01). HOMA-index improved from 5.2+/-3.4 to 1.5+/-1.0 (p<0.01). Calcium concentrations slightly decreased, and phosphate increased (-0.06+/-0.13 mmol/l and +0.08+/-0.16 mmol/l, respectively; both p<0.05), while 25-OH-Vitamin D3 remained unchanged and PTH tended to increase (+5.1+/-14.0 pg/ml, p=0.054). Monocyte chemoattractant protein 1 and interleukin 18 were significantly decreased and associated with HOMA both before and after bariatric surgery. DeltaOPN was correlated with DeltaPTH, but not with other parameters. OPN plasma concentrations increased concomitant to weight loss after bariatric surgery, which was independent from an improvement of insulin sensitivity and a decrease of inflammatory markers. Further studies are needed to differentiate whether these changes in bone metabolism after bariatric surgery are secondary to calcium deficiency or an adaptation to weight loss.
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    ABSTRACT: 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. OPN and CD44 expressions were studied in 52 morbidly obese patients and in mice. Cellular studies were performed in HepG2 cells. 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. 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.
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