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Am J Physiol Endocrinol Metab 283: E556-E564, 2002; doi:10.1152/ajpendo.00127.2002
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Vol. 283, Issue 3, E556-E564, September 2002

Normal insulin sensitivity and IMCL content in overweight humans are associated with higher fasting lipid oxidation

Gianluca Perseghin1,2, Paola Scifo2,3,4, Massimo Danna2,3,4, Alberto Battezzati1,5, Stefano Benedini1, Elena Meneghini1, Alessandro Del Maschio2,4, and Livio Luzi1,2

Divisions of 1 Nutrition/Metabolism, 3 Nuclear Medicine, 4 Diagnostic Radiology, and 2 Unit of Clinical Spectroscopy, Università Vita e Salute San Raffaele, Istituto Scientifico H San Raffaele, 20132 Milan; and 5 International Center for the Assessment of Nutritional Status, Università degli Studi di Milano, 20133 Milan, Italy

Intramyocellular lipid (IMCL) storage is considered a local marker of whole body insulin resistance; because increments of body weight are supposed to impair insulin sensitivity, this study was designed to assess IMCL content, lipid oxidation, and insulin action in individuals with a moderate increment of body fat mass and no family history of diabetes. We studied 14 young, nonobese women with body fat <30% (n = 7) or >30% (n = 7) and 14 young, nonobese men with body fat <25% (n = 7) or >25% (n = 7) by means of the euglycemic-insulin clamp to assess whole body glucose metabolism, with indirect calorimetry to assess lipid oxidation, by localized 1H NMR spectroscopy of the calf muscles to assess IMCL content, and with dual-energy X-ray absorptiometry to assess body composition. Subjects with higher body fat had normal insulin-stimulated glucose disposal (P = 0.80), IMCL content in both soleus (P = 0.22) and tibialis anterior (P = 0.75) muscles, and plasma free fatty acid levels (P = 0.075) compared with leaner subjects in association with increased lipid oxidation (P < 0.05), resting energy expenditure (P = 0.046), resting oxygen consumption (P = 0.049), and plasma leptin levels (P < 0.01) in the postabsorptive condition. In conclusion, in overweight subjects, preservation of insulin sensitivity was combined with increased lipid oxidation and maintenance of normal IMCL content, suggesting that abnormalities of these factors may mutually determine the development of insulin resistance associated with weight gain.

intramyocellular lipid content; lipid oxidation; insulin resistance; leptin; tumor necrosis factor-alpha ; nuclear magnetic resonance spectroscopy


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