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

Authors: Krout, Danielle; Roemmich, James; GARCIA, ROLANDO - Former ARS Employee; Bundy, Amy; Yan, Lin; Larson, Kate

Submitted to: Journal of Nutritional Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/8/2018
Publication Date: 7/1/2018
Citation: Krout, D.P., Roemmich, J.N., Garcia, R.A., Bundy, A.N., Yan, L., Larson, K.J. 2018. Paternal exercise protects mouse offspring from high-fat-diet-induced type 2 diabetes risk by increasing skeletal muscle insulin signaling. Journal of Nutritional Biochemistry. 57:35-44. https://doi.org/10.1016/j.jnutbio.2018.03.013.
DOI: https://doi.org/10.1016/j.jnutbio.2018.03.013

Interpretive Summary: In this manuscript, we describe how paternal exercise reduces type 2 diabetes (T2D) risk in offspring and, when coupled with a paternal high-fat (HF) diet, increases insulin signaling in the skeletal muscle of offspring. Previously, several studies indicated that paternal obesity increases, while paternal exercise decreases, offspring obesity and type 2 diabetes risk; however, none had yet to determine whether a paternal HF diet and exercise interact to alter offspring body weight, adiposity, and T2D risk. Results presented in this study show that male offspring of fathers that exercised had significantly reduced T2D risk and that when fathers were fed a HF diet and exercised, a postnatal HF diet resulted in increased adipocyte called beige adipocyte that has higher level of metabolism. Furthermore, offspring of fathers that were fed a HF diet and exercised had increased expression of insulin signaling markers in skeletal muscle suggesting that paternal exercise is required to protect mouse offspring from high-fat diet-induced T2D risk.

Technical Abstract: Paternal obesity has been shown to increase, 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 control diet (16% fat) or a high fat diet (45% fat) and assigned to either voluntary wheel running exercise or cage activity for 3 months prior to mating with control diet fed dams. After weaning, male offspring were fed a control or HF diet for an additional 3 months. F1 male mice whose fathers ate a HF diet had decreased BW and % body fat accompanied by decreased gene expression of a beige adipocyte marker, FGF21. However, whereas paternal exercise and postnatal NF diet significantly reduced T2D risk, paternal HF diet-induced reductions in BW and % body fat did not reduce T2D risk of F1 offspring due to increased expression of insulin signaling markers in skeletal muscle (GLUT4, IRS1, and PI3K). When fathers were fed a HF diet and exercised, a postnatal HF diet resulted in increased beiging, while a postnatal HF diet alone increased BW and % body fat accompanied by increased adipogenesis (PPAR gamma). Thus, these findings show that paternal exercise reduces T2D risk in offspring and, when coupled with paternal HF diet, increases insulin signaling in F1 skeletal muscle. Future studies should determine the physiological mechanism(s) underlying the beneficial effects of exercise through the paternal lineage.