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

Abstract

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 (1)H 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.

Reduced whole-body lipid oxidation is associated with insulin resistance, but not with intramyocellular lipid content in offspring of type 2 diabetic patients

“…An impairment of fasting lipid oxidation in association with insulin resistance and IMCL accumulation may also be seen as a secondary consequence of metabolic disturbances [9]. The reverse metabolic picture was described by our group in healthy humans in whom, despite a moderate degree of overweight, insulin sensitivity and normal IMCL content were preserved in association with higher fasting lipid oxidation [10]. Moreover using a longitudinal approach, it was shown that in obese individuals enhanced insulin sensitivity through physical activity was associated with increased fat oxidation [11,12].…”

“…Blood samples for postabsorptive plasma glucose, total cholesterol, triglycerides, NEFA, insulin, α-tumour necrosis factor receptor-2 (α-TNFR-2), leptin and adiponectin were performed in duplicate in the postabsorptive condition. Following a 150-min tracer equilibration period, a euglycaemic-hyperinsulinaemic clamp was performed as previously described [10,14] for a 150-min period using an insulin infusion rate of 40 mU·m −2 ·min −1 . Blood samples for plasma hormones, substrates and tracer enrichment were drawn every 15 min throughout the study.…”

“…H-magnetic resonance spectroscopy This was performed on a GE Signa 1.5 Tesla scanner (General Electric Medical Systems, Milwaukee, WI, USA) using a conventional linear extremity coil as previously described [3,10,14]. Briefly, two 1 H spectra were collected from a 15×15×15 mm volume within the soleus and tibialis anterior muscles respectively, using a PRESS pulse sequence (TR=2,000 ms and TE=60 ms) and 128 averages were accumulated for each spectrum with a final acquisition time of 4.5 min.…”

“…A third 1 H spectrum of a triglyceride solution inside a glass sphere, positioned within the extremity coil next to the calf, was also obtained during the same session in order to have an external standard acquired in the same conditions as the subject's spectra. Postprocessing of the data, executed with Sage/IDL software (GE Medical Systems) was performed as previously described [3,10,14]. The T2 (spinspin relaxation time) value of the muscle -CH 2 signal of the IMCL compartment was measured in five lean and four overweight individuals, in whom signal intensities were obtained at six different TEs chosen to linearly fit a monoexponential function, and was found to be not different between the subjects.…”

Is a nutritional therapeutic approach unsuitable for metabolically healthy but obese women?

“…Initially, investigators focused on elucidating the mechanism underlying this protective effect, with the aim of identifying potential therapeutic targets for the treatment of obese and insulinresistant individuals. It was reported that a lower visceral fat content, despite a high body fat content, and a lower accumulation of fat within ectopic sites may contribute to the favourable metabolic profile [2,4]. These metabolically healthy but obese postmenopausal women had lower circulating levels of high-sensitivity C-reactive protein compared with 'at-risk' women [5], suggesting that the lack of a systemic proinflammatory condition, common in obesity, may explain the protection.…”