CC002/Unc females are mouse models of exercise-induced paradoxical fat response

Rachel C. McMullan, Martin T. Ferris, Timothy A. Bell, Vineet D. Menachery, Ralph S. Baric, Kunjie Hua, Daniel Pomp, Abbie E. Smith-Ryan, Fernando Pardo Manuel de Villena

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Exercise results in beneficial health outcomes and protects against a variety of chronic diseases. However, U.S. exercise guidelines recommend identical exercise programs for everyone, despite individual variation in responses to these programs, including paradoxical fat gain. Experimental models of exercise-induced paradoxical outcomes may enable the dissection of underlying physiological mechanisms as well as the evaluation of potential interventions. Whereas several studies have identified individual mice exhibiting paradoxical fat gain following exercise, no systematic effort has been conducted to identify and characterize models of paradoxical response. Strains from the Collaborative Cross (CC) genetic reference population were used due to its high levels of genetic variation, its reproducible nature, and the observation that the CC is a rich source of novel disease models, to assess the impact genetic background has on exercise responses. We identified the strain CC002/Unc as an exercise-induced paradoxical fat response model in a controlled voluntary exercise study across multiple ages in female mice. We also found sex and genetic differences were consistent with this pattern in a study of forced exercise programs. These results provide a novel model for studies to determine the mechanisms behind paradoxical metabolic responses to exercise, and enable development of more rational personalized exercise recommendations based on factors such as age, sex, and genetic background.

Original languageEnglish (US)
Article numbere13716
JournalPhysiological reports
Issue number12
StatePublished - Jun 2018
Externally publishedYes


  • Body composition
  • Collaborative Cross
  • genetic background
  • high intensity interval training
  • moderate intensity continuous training

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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