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

Abstract

Key points A paternal high‐fat diet/obesity before mating can negatively influence the metabolism of offspring. Exercise only early in life has a remarkable effect with respect to reprogramming adult rat offspring exposed to detrimental insults before conception. Exercise only early in life normalized adult whole body and muscle insulin resistance as a result of having a high‐fat fed/obese father. Unlike the effects on the muscle, early exercise did not normalize the reduced adult pancreatic beta cell mass as a result of having a high‐fat fed/obese father. Early‐life exercise training may be able to reprogram an individual whose father was obese, inducing long‐lasting beneficial effects on health. Abstract A 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−1, 60 min day−1, 20 m min−1) from 5 to 9 weeks of age. Paternal HFD impaired (P < 0.05) adult offspring whole body insulin sensitivity (i.p. insulin sensitivity test), as well as 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 i.p. glucose tolerance test. Early‐life exercise in offspring reprogrammed the negative effects of a paternal HFD on whole body insulin sensitivity, skeletal muscle ex vivo insulin‐stimulated glucose uptake and TBC1D4 phosphorylation and also increased glucose transporter 4 protein. However, early exercise did not normalize 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 HFD without affecting pancreatic β‐cell mass or insulin secretion.

Risk of hypertension following perinatal adversity: IUGR and prematurity

“…There is evidence that specific doses of exercise, administered by physical therapists, can at least transiently improve the growth and bone density of premature infants (Schulzke et al 2014). Encouragingly, in rodents, the early introduction of physical activity has been shown to improve the metabolic health of individuals exposed to an antenatal high-fat diet (Falcão-Tebas et al 2019).…”

Classic solutions to a modern problem: exercise training improves metabolic disorders in offspring from fathers on a high fat diet

“…In the present issue of The Journal of Physiology , Falcão‐Tebas et al . () eloquently show that paternal diet and early lifestyle are critical factors in determining the future metabolic fitness of the offspring. Falcão‐Tebas and colleagues demonstrate that male rats fed a diet rich in fat sire female offspring with metabolic complications and that moderate exercise during adolescence can reprogram some preexisting complications from paternal programming mechanisms.…”

“…Falcão‐Tebas and colleagues present compelling evidence on the impact of paternal high fat diet on endocrine function in adult offspring, despite a healthy intrauterine milieu. In addition to establishing that paternal high fat diet causes glucose intolerance in adult offspring, the authors provide a feasible 4‐week exercise intervention that can be easily translated into humans following expeditious investigation in larger animal models that more closely resemble human development.…”

“…Falcão‐Tebas and colleagues investigated contributing factors that link perturbations in insulin sensitivity and glucose tolerance to cellular metabolism and insulin signaling (phosphorylation of Akt Ser473 ) in skeletal muscle. The authors demonstrate enhanced glucose uptake in isolated skeletal muscle and increased rates of oxygen consumption in mitochondria from all offspring that underwent early life exercise training.…”

“…Although the original work primarily focused on mechanisms underlying fetal adaptations from maternal insults, contributions from preexistent paternal stress in the form of body composition or environmental toxins have been less robust, with few groups proposing interventions. In the present issue of The Journal of Physiology, Falcão-Tebas et al (2019) eloquently show that paternal diet and early lifestyle are critical factors in determining the future metabolic fitness of the offspring. Falcão-Tebas and colleagues demonstrate that male rats fed a diet rich in fat sire female offspring with metabolic complications and that moderate exercise during adolescence can reprogram some preexisting complications from paternal programming mechanisms.…”