Markers of Mitochondrial Biogenesis and Metabolism Are Lower in Overweight and Obese Insulin-Resistant Subjects
Leonie K. Heilbronn,
Seng Khee Gan,
Nigel Turner,
Lesley V. Campbell and
Donald J. Chisholm
Diabetes and Obesity Research Program (L.K.H., N.T., L.V.C., D.J.C.), Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia; Royal Perth Hospital (S.K.G.), School of Medicine and Pharmacology, Perth, Western Australia 6001, Australia; and School of Health Sciences (N.T.), University of Wollongong, Wollongong, New South Wales 2522, Australia
Address all correspondence and requests for reprints to: Dr. Leonie Heilbronn, Garvan Institute for Medical Research, 384 Victoria Street, Darlinghurst, New South Wales 2010, Australia. E-mail: l.heilbronn{at}garvan.org.au.
Background: Impaired mitochondrial function in skeletal muscleis implicated in the development of insulin resistance. However,potential differences in fatness and fitness may influence previousresults.
Methods: Subjects (n =18) were divided into insulin-sensitive(IS) and insulin-resistant (IR) groups by median glucose infusionrate during a hyperinsulinemic euglycemic clamp. Weight, VO2max(maximal aerobic capacity), and percentage body fat were measuredbefore and after 6 continuous weeks of aerobic exercise trainingat 55–70% VO2max (40 min/session, 4 d/wk).
Results: Age, percentage fat, and VO2max were not differentbetween IS and IR groups at baseline. Expression of the nuclearencoded PGC1 and mitochondrial encoded gene COX1 were significantlylower in the IR group (P < 0.05). Citrate synthase activityand protein levels of subunits from complexes I and III of therespiratory chain were also lower in the IR group (P < 0.05).Insulin sensitivity and aerobic fitness were increased afterexercise training in both groups (P < 0.001), and the expressionof mitochondrial encoded genes CYTB and COX1 was also increased(P < 0.01). However, there was no change in PGC1 expression,mitochondrial enzyme activity, or protein levels of complexesof the respiratory chain in response to exercise in either group.
Conclusion: This study confirms that IR men have reduced markersof mitochondrial metabolism, independent of fatness and fitness.Moderate exercise training did not alter these markers despiteimproving fitness and whole body insulin sensitivity. This studysuggests that additional mechanisms may be involved in improvinginsulin resistance after exercise training in obese men.
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and mitochondrial encoded gene COX1 were significantly lower in the IR group (P < 0.05). Citrate synthase activity and protein levels of subunits from complexes I and III of the respiratory chain were also lower in the IR group (P < 0.05). Insulin sensitivity and aerobic fitness were increased after exercise training in both groups (P < 0.001), and the expression of mitochondrial encoded genes CYTB and COX1 was also increased (P < 0.01). However, there was no change in PGC1
