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Moderate Daily Exercise Activates Metabolic Flexibility to Prevent Prenatally Induced Obesity

Liggins Institute (J.L.M., N.M.T., M.D., B.H.B.), National Research Centre for Growth and Development (J.L.M., B.H.B.), Department of Surgery (N.M.T.), Faculty of Medical and Health Sciences, and Department of Psychology (M.D.), Faculty of Science, The University of Auckland, 1142 Auckland, New Zealand; and Department of Physiology (K.H.), School for Veterinary Medicine, 30625 Hannover, Germany

Address all correspondence and requests for reprints to: Bernhard Breier, Ph.D., Institute of Food, Nutrition, and Human Health, Massey University, Private Bag 102-904 North Shore Mail Centre, 1142 Auckland, New Zealand. E-mail: b.brier{at}massey.ac.nz.

Obesity and its associated comorbidities are of major worldwide concern. It is now recognized that there are a number of metabolically distinct pathways of obesity development. The present paper investigates the effect of moderate daily exercise on the underlying mechanisms of one such pathway to obesity, through interrogation of metabolic flexibility. Pregnant Wistar rats were either fed chow ad libitum or undernourished throughout pregnancy, generating control or intrauterine growth restricted (IUGR) offspring, respectively. At 250 d of age, dual-emission x-ray absorptiometry scans and plasma analyses showed that moderate daily exercise, in the form of a measured amount of wheel running (56 m/d), prevented the development of obesity consistently observed in nonexercised IUGR offspring. Increased plasma C-peptide and hepatic atypical protein kinase C levels explained increased glucose uptake and increased hepatic glycogen storage in IUGR offspring. Importantly, whereas circulating levels of retinol binding protein 4 were elevated in obese, nonexercised IUGR offspring, indicative of glucose sparing without exercise, retinol binding protein 4 levels were normalized in the exercised IUGR group. These data suggest that IUGR offspring have increased flexibility of energy storage and use and that moderate daily exercise prevents obesity development through activation of distinct pathways of energy use. Thus, despite a predisposition to develop obesity under sedentary conditions, obesity development was prevented in IUGR offspring when exercise was available. These results emphasize the importance of tailored lifestyle changes that activate distinct pathways of metabolic flexibility for obesity prevention.

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