Effects of early-life exposure to Western diet and voluntary exercise on adult activity levels, exercise physiology, and associated traits in selectively bred High Runner mice

• Published in: Physiology & behavior 2021-05, Vol.234, p.113389-113389, Article 113389
• Main Authors: Cadney, Marcell D., Hiramatsu, Layla, Thompson, Zoe, Zhao, Meng, Kay, Jarren C., Singleton, Jennifer M., Albuquerque, Ralph Lacerda de, Schmill, Margaret P., Saltzman, Wendy, Garland, Theodore
• Format: Article
• Language: English
• Subjects: Adiposity; Animals; Developmental programming; Diet, Western - adverse effects; Early-life effects; Exercise; Mice; Mice, Inbred Strains; Motor Activity; Phenotype; Reward; Western diet; Wheel running
• ISSN: 0031-9384; 1873-507X
• DOI: 10.1016/j.physbeh.2021.113389

•Subjects were selectively bred High Runner (HR) and non-selected Control (C) mice.•Juveniles were housed with/without wheels and given standard or Western diet (WD).•After 8 weeks washout, early-life WD increased adult wheel running only in HR mice.•Early exercise increased muscle and brain mass, and reduced anxiety-like behavior.•Early-life WD increased adult preference for WD but not for sucrose. Exercise behavior is under partial genetic control, but it is also affected by numerous environmental factors, potentially including early-life experiences whose effects persist into adulthood. We studied genetic and early-life environmental effects on wheel-running behavior in a mouse model that includes four replicate high runner (HR) lines selectively bred for increased voluntary wheel running as young adults and four non-selected control (C) lines. In a full factorial design, mice from each line were granted wheel access or not and administered either standard or Western diet (WD) from weaning (3 weeks old) to 6 weeks of age (sexual maturity). In addition to acute effects, after a washout period of 8 weeks (∼6 human years) in which all mice had standard diet and no wheel access, we found both beneficial and detrimental effects of these early-life exposures. During the first week of treatments, WD increased distance run by 29% in C mice and 48% in HR mice (significant Diet × Linetype interaction), but diet effects disappeared by the third week. Across the three weeks of juvenile treatment, WD significantly increased fat mass (with lean mass as a covariate). Tested as adults, early-life exercise increased wheel running of C mice but not HR mice in the first week. Early-life exercise also reduced adult anxiety-like behavior and increased adult fasted blood glucose levels, triceps surae mass, subdermal fat pad mass, and brain mass, but decreased heart ventricle mass. Using fat mass as a covariate, early-life exercise treatment increased adult leptin concentration. In contrast, early-life WD increased adult wheel running of HR mice but not C mice. Early-life WD also increased adult lean mass and adult preference for Western diet in all groups. Surprisingly, early-life treatment had no significant effect on adult body fat or maximal aerobic capacity (VO2max). No previous study has tested for combined or interactive effects of early-life WD and exercise. Our results demonstrate that both factors can have long-lasting effects on adult voluntary exercise and related