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Markers of Mitochondrial Biogenesis and Metabolism Are Lower in Overweight and Obese Insulin-Resistant Subjects

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 muscle is implicated in the development of insulin resistance. However, potential differences in fatness and fitness may influence previous results.

Methods: Subjects (n =18) were divided into insulin-sensitive (IS) and insulin-resistant (IR) groups by median glucose infusion rate during a hyperinsulinemic euglycemic clamp. Weight, VO_2max (maximal aerobic capacity), and percentage body fat were measured before and after 6 continuous weeks of aerobic exercise training at 55–70% VO_2max (40 min/session, 4 d/wk).

Results: Age, percentage fat, and VO_2max were not different between IS and IR groups at baseline. Expression of the nuclear encoded PGC1 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 expression, mitochondrial enzyme activity, or protein levels of complexes of the respiratory chain in response to exercise in either group.

Conclusion: This study confirms that IR men have reduced markers of mitochondrial metabolism, independent of fatness and fitness. Moderate exercise training did not alter these markers despite improving fitness and whole body insulin sensitivity. This study suggests that additional mechanisms may be involved in improving insulin resistance after exercise training in obese men.

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