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This Article Full Text Full Text (PDF) All Versions of this Article: 297/2/E552    most recent 00220.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Solomon, T. P. J. Articles by Kirwan, J. P. PubMed PubMed Citation Articles by Solomon, T. P. J. Articles by Kirwan, J. P.

Effects of exercise training and diet on lipid kinetics during free fatty acid-induced insulin resistance in older obese humans with impaired glucose tolerance

¹Department of Pathobiology, Lerner Research Institute; ²Department of Gastroenterology/Hepatology, Cleveland Clinic, Cleveland, Ohio; ³Division of Cardiology, University of Maryland School of Medicine, Baltimore, Maryland; ⁴Department of Nutrition, Case Western Reserve School of Medicine; and ⁵Department of Physiology, Case Western Reserve University, Cleveland, Ohio

Submitted 3 April 2009 ; accepted in final form 12 June 2009

Elevated free fatty acids (FFA) are implicated with insulin resistance at the cellular level. However, the contribution of whole body lipid kinetics to FFA-induced insulin resistance is not well understood, and the effect of exercise and diet on this metabolic defect is not known. We investigated the effect of 12 wk of exercise training with and without caloric restriction on FFA turnover and oxidation (FFA_ox) during acute FFA-induced insulin resistance. Sixteen obese subjects with impaired glucose tolerance were randomized to either a hypocaloric (n = 8; –598 ± 125 kcal/day, 66 ± 1 yr, 32.8 ± 1.8 kg/m²) or a eucaloric (n = 8; 67 ± 2 yr, 35.3 ± 2.1 kg/m²) diet and aerobic exercise (1 h/day at 65% of maximal oxygen uptake) regimen. Lipid kinetics ([1-¹⁴C]palmitate) were assessed throughout a 7-h, 40 mU·m^–2·min^–1 hyperinsulinemic euglycemic clamp, during which insulin resistance was induced in the last 5 h by a sustained elevation in plasma FFA (intralipid/heparin infusion). Despite greater weight loss in the hypocaloric group (–7.7 ± 0.5 vs. –3.3 ± 0.7%, P < 0.001), FFA-induced peripheral insulin resistance was improved equally in both groups. However, circulating FFA concentrations (2,123 ± 261 vs. 1,764 ± 194 µmol/l, P < 0.05) and FFA turnover (3.20 ± 0.58 vs. 2.19 ± 0.58 µmol·kg FFM^–1·min^–1, P < 0.01) during hyperlipemia were suppressed only in the hypocaloric group. In contrast, whole body FFA_ox was improved in both groups at rest and during hyperlipemia. These changes were driven by increases in intracellular lipid-derived FFA_ox (12.3 ± 7.7 and 14.7 ± 7.8%, P < 0.05). We conclude that the exercise-induced improvement in FFA-induced insulin resistance is independent of the magnitude of weight loss and FFA turnover, yet it is linked to increased intracellular FFA utilization.

lipid-induced insulin resistance; palmitate turnover; palmitate oxidation; diabetes; obesity; aging; physical activity