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J Physiol. 2018 Nov 8. doi: 10.1113/JP276386. [Epub ahead of print]

Four weeks of exercise early in life reprograms adult skeletal muscle insulin resistance caused by paternal high fat diet.

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Institute for Health and Sport (IHES), Victoria University, Melbourne, Australia.
The Ritchie Centre, Hudson Institute of Medical Research, and Department of Obstetrics and Gynaecology, Monash University, Melbourne, Australia.
Department of Medicine, Austin Hospital, The University of Melbourne, Melbourne, Australia.
College of Health and Biomedicine, Victoria University, Melbourne, Australia.



Paternal high fat diet/obesity before mating can negatively influence the metabolism of offspring. Exercise only early in life has a remarkable effect to reprogram adult rat offspring exposed to detrimental insults before conception. Exercise only early in life normalized adult whole body and muscle insulin resistance due to having a high fat fed/obese father. Unlike the effects on the muscle, early exercise did not normalise the reduced adult pancreatic beta cell mass due to having a high fat fed/obese father. Early life exercise training may be able to reprogram the individual whose father was obese, inducing long-lasting beneficial effects on health.


Paternal high fat diet (HFD) impairs female rat offspring glucose tolerance, pancreatic morphology and insulin secretion. We examined whether only 4 weeks of exercise early in life could reprogram these negative effects. Male Sprague-Dawley rats consumed a HFD for 10 weeks before mating with chow-fed dams. Female offspring remained sedentary or performed moderate intensity treadmill exercise (5 days/week, 60 min/day, 20 m/min) from 5 to 9 weeks of age. Paternal HFD impaired (P<0.05) adult offspring whole body insulin sensitivity (intraperitoneal insulin sensitivity test) and skeletal muscle ex vivo insulin sensitivity and TBC1D4 phosphorylation. It also lowered β-cell mass and reduced in vivo insulin secretion in response to an intraperitoneal glucose tolerance test. Early life exercise in offspring reprogrammed the negative effects of paternal HFD on whole body insulin sensitivity, skeletal muscle ex vivo insulin-stimulated glucose uptake and TBC1D4 phosphorylation and increased GLUT4 protein. However, early exercise did not normalise the reduced pancreatic β-cell mass or insulin secretion. In conclusion, only 4 weeks of exercise early in life in female rat offspring reprograms reductions in insulin sensitivity in adulthood caused by a paternal high fat diet without affecting pancreatic β-cell mass or insulin secretion. This article is protected by copyright. All rights reserved.


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