Abstract
Objective:Overexpression of Angiopoietin-like protein 2 (Angptl2) in obese adipose tissues promotes adipose tissue inflammation and its-related metabolic abnormalities. In a comparative study with adiponectin, we investigated whether alterations in serum Angptl2 concentrations reflect the effect of lifestyle intervention on weight loss and improved metabolic parameters in overweight subjects.Methods:A total of 154 Japanese men (age, 40.9±5.1 years; body mass index, 26.9±3.6 kg m−2; abdominal circumference, 94.1±8.9 cm) underwent a 3-month lifestyle intervention and underwent follow-up for 3 months thereafter.Results:Decreased serum Angptl2 levels, but not increased serum adiponectin levels, were immediately apparent at the end of 3-month lifestyle intervention. Angptl2 levels continued to decrease for 3 months in parallel with body weight loss and improvement in metabolic indicators. In subjects showing ⩾6% weight reduction, markedly reduced Angptl2 levels were detected at the end of 3-month intervention, whereas increased adiponectin levels were detected 3 months after the end of intervention. Multivariate analysis revealed changes in serum Angptl2 levels associated with changes in triglycerides (TGs), aspartate aminotransferase and alanine aminotransferase. In contrast, changes in serum adiponectin levels were associated with altered high-density lipoprotein cholesterol (HDL-C) and fasting plasma glucose levels.Conclusion:A 3-month lifestyle intervention promoted weight reduction and improved glucose and lipid metabolism, an effect maintained 3 months later. Notably, our findings indicate that decreased Angptl2 levels are a good indicator of reduced visceral fat and metabolic improvement at early stages of lifestyle intervention. Thus, Angptl2 reflects adiposity and might be a key protein to regulate inflammation and TG metabolism, whereas adiponectin levels could reflect improved glucose and HDL-C metabolism.
Highlights
Circulating levels of C-reactive protein (CRP), fibrinogen and some adipose tissue-derived cytokines, all associated with inflammation, are decreased by body weight reduction, an occurrence associated with improved insulin resistance.[6,16,17,18,19]
We observed significant decreases in circulating Angptl[2] concentrations in obese diabetic men following treatment with the PPARg agonist pioglitazone, and the percent decrease in Angptl[2] levels was positively correlated with the percent decreases in visceral fat area. These findings suggest that visceral fat is a likely primary source of circulating Angptl[2] and that levels of that factor are significantly correlated with systemic insulin resistance and inflammation.[20,21,22]
We monitored the influence of weight reduction on adiponectin levels, which reportedly increase in the circulation with weight loss and serve as a biomarker to assess the improvement of obesity and its-related metabolic abnormalities.[6,7,8,9]
Summary
Angptl[2] vs weight reduction A Muramoto et al[2] normal in cases of obesity in human and mice, in cases with visceral fat accumulation, leading to chronic adipose tissue inflammation and subsequent development or progression of insulin resistance and metabolic syndrome.[20,21,22] We observed accumulation of fat in the liver and skeletal muscle was mild in Angptl[2] knockout mice compared with wild-type mice, and Angptl[2] deletion ameliorated adipose tissue inflammation.[20] We observed significant decreases in circulating Angptl[2] concentrations in obese diabetic men following treatment with the PPARg agonist pioglitazone, and the percent decrease in Angptl[2] levels was positively correlated with the percent decreases in visceral fat area. We monitored the influence of weight reduction on adiponectin levels, which reportedly increase in the circulation with weight loss and serve as a biomarker to assess the improvement of obesity and its-related metabolic abnormalities.[6,7,8,9]
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