Paternal exercise protects mouse offspring from high-fat-diet-induced type 2 diabetes risk by increasing skeletal muscle insulin signaling

Abstract

Paternal obesity increases, while paternal exercise decreases, offspring obesity and type 2 diabetes (T2D) risk; however, no studies have determined whether a paternal high-fat (HF) diet and exercise interact to alter offspring body weight (BW), adiposity and T2D risk. Three-week-old male C57BL/6 mice were fed a normal-fat (NF) diet (16% fat) or an HF diet (45% fat) and assigned to either voluntary wheel running exercise or cage activity for 3 months prior to mating with NF-diet-fed dams. After weaning, male offspring were fed an NF or HF diet for an additional 3 months. F1 male mice whose fathers ate an HF diet had decreased % body fat accompanied by decreased gene expression of beige adipocyte marker FGF21. However, paternal HF-diet-induced reductions in F1 offspring % body fat normalized but did not reduce T2D risk. Exercise was protective against paternal HF-diet-induced insulin resistance by increasing the expression of insulin signaling (GLUT4, IRS1 and PI3K) markers in skeletal muscle resulting in normal T2D risk. When fathers were fed an HF diet and exercised, a postnatal HF diet increased beiging (PPARγ). Thus, these findings show that increases in T2D risk in male offspring when the father consumes an HF diet can be normalized when the father also exercises preconception and that this protection may occur by increases in insulin signaling potential within offspring skeletal muscle. Future studies should further determine the physiological mechanism(s) underlying the beneficial effects of exercise through the paternal lineage.

Paternal Resistance Training Induced Modifications in the Left Ventricle Proteome Independent of Offspring Diet

“…Paternal RT did not result in decreased glucose AUC. Krout et al [11] showed that paternal exercise was protective against insulin resistance by increasing the expression of insulin signaling markers in skeletal muscle resulting in normal T2D risk in offspring. The difference between the present study and Krout et al [11] is the utilization of animals from different species.…”

“…Krout et al [11] showed that paternal exercise was protective against insulin resistance by increasing the expression of insulin signaling markers in skeletal muscle resulting in normal T2D risk in offspring. The difference between the present study and Krout et al [11] is the utilization of animals from different species. The C57BL/6J lineage mice respond more pronouncedly to HF diet, which can facilitate insulin resistance when compared to Wistar rats [50].…”

“…Exercise is an important piece in the obesity puzzle, representing a potent regulator of transgenerational inheritance for health and disease risk [10]. Krout et al [11] reported in mice that paternal preconceptional exercise (2 weeks of wheel running) prevented the increase of type 2 diabetes risk in the offspring after paternal HF diet. This protection may occur by increases in the expression of insulin signaling pathways in the skeletal muscle of the offspring.…”

Paternal Resistance Training Modulates Calcaneal Tendon Proteome in the Offspring Exposed to High-Fat Diet

“…A recent study indicates that voluntary paternal exercise (running wheel) suppresses the detrimental effects of paternal HF diet on offspring, reducing the harmful effects on glucose tolerance, fat mass and glucose uptake in different skeletal muscles (Stanford et al, 2018). Krout et al (2018) demonstrate that paternal exercise (2 weeks of wheel running) increases the expression of insulin signaling pathways in offspring skeletal muscle, what can be an important tool to prevention type 2 diabetes. Although highly significant, the authors did not strictly manipulate training variables (duration, intensity, rest interval, training volume), which could amplify the understanding of exercise dose on metabolic variables, and tendon offspring.…”

“…Ancestral environmental conditions can elicit lifelong effects on the offspring physiology, including increased susceptibility to the obesity and metabolic disorders development (Krout et al, 2018;Winther et al, 2018;Glendining and Jasoni, 2019). Although detrimental effects of maternal obesity during perinatal periods on adiposity and metabolic function in offspring are well established, paternal lifestyle may also influence offspring developmental outcomes.…”