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1 Internal Medicine - Section of Nutrition/Metabolism, Istituto Scientifico H San Raffaele, Milan, Italy; Unit of Clinical Spectroscopy, Istituto Scientifico H San Raffaele, Milan, Italy; Center Physical exercise for health and wellness, Universita' degli Studi di Milano, Milan, Italy
2 Division of Pediatrics, Istituto Scientifico H San Raffaele, Milan, Italy
3 Internal Medicine - Section of Nutrition/Metabolism, Istituto Scientifico H San Raffaele, Milan, Italy
4 Diagnostic Radiology, Istituto Scientifico H San Raffaele, Milan, Italy; Unit of Clinical Spectroscopy, Istituto Scientifico H San Raffaele, Milan, Italy
5 Diagnostic Radiology, Istituto Scientifico H San Raffaele, Milan, Italy
6 Nuclear Medicine, Istituto Scientifico H San Raffaele, Milan, Italy
7 Diagnostic Radiology, Istituto Scientifico H San Raffaele, Milan, Italy; Unit of Clinical Spectroscopy, Istituto Scientifico H San Raffaele, Milan, Italy; Universita' Vita e Salute San Raffaele, Milan, Italy
8 Division of Pediatrics, Istituto Scientifico H San Raffaele, Milan, Italy; Universita' Vita e Salute San Raffaele, Milan, Italy
9 Internal Medicine - Section of Nutrition/Metabolism, Istituto Scientifico H San Raffaele, Milan, Italy; Faculty of Exercise Sciences, Universita' degli Studi di Milano, Milan, Italy; Center Physical exercise for health and wellness, Universita' degli Studi di Milano, Milan, Italy
* To whom correspondence should be addressed. E-mail: perseghin.gianluca{at}hsr.it.
Obese adolescents are at risk of developing nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes. We measured non-invasively the intra-hepatic fat (IHF) content of obese adolescents to ascertain whether is associated with insulin resistance and abnormal energy homeostasis. IHF content, whole body energy homeostasis, insulin sensitivity and body composition were measured using localized hepatic 1H-MRS, indirect calorimetry, fasting-derived and 3-hours OGTT-derived surrogate indexes (HOMA-2 and WBISI), and DXA respectively, in 54 obese adolescents (24F/30M, age: 13±2 ys, BMI > 99th percentile for their age and sex). NAFLD (defined as IHF content >5% wet weight) was found in 16 individuals (30%) in association with higher alanine-aminotransferase (P<0.006), HbA1c (P=0.021), trunk fat content (P<0.03) and lower HDL-chol (P<0.05). Individuals with NAFLD had higher fasting plasma glucose (89±8 vs. 83±9 mg/dl; P=0.01) and impaired insulin sensitivity (HOMA-2 and WBISI; P<0.05) meanwhile parameters of insulin secretion were unaffected. Their reliance on fat oxidation in the fasting state was lower (respiratory quotient 0.83±0.08 vs. 0.77±0.05; P<0.01) and their ability to suppress it during the oral glucose challenge was impaired (P<0.05) in comparison with those with normal IHF content. When controlling for trunk fat content, the correlation between the IHF content and insulin sensitivity was weakened meanwhile the correlation with fasting lipid oxidation was maintained. In conclusion, NAFLD is common in childhood obesity and insulin resistance is present in association with increased trunk fat content. In contrast, the re-arrangement of whole body substrates oxidation in these youngsters appeared to be an independent feature.
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