Downhill Running-Based Overtraining Protocol Improves Hepatic Insulin Signaling Pathway without Concomitant Decrease of Inflammatory Proteins

Alisson L da Rocha; Bruno C Pereira; José R Pauli; Dennys E Cintra; Claudio T de Souza; Eduardo R Ropelle; Adelino S R da Silva

doi:10.1371/journal.pone.0140020

Downhill Running-Based Overtraining Protocol Improves Hepatic Insulin Signaling Pathway without Concomitant Decrease of Inflammatory Proteins

PLoS One. 2015 Oct 7;10(10):e0140020. doi: 10.1371/journal.pone.0140020. eCollection 2015.

Authors

Alisson L da Rocha¹, Bruno C Pereira¹, José R Pauli², Dennys E Cintra², Claudio T de Souza³, Eduardo R Ropelle², Adelino S R da Silva⁴

Affiliations

¹ Postgraduate Program in Rehabilitation and Functional Performance, RibeirãoPreto Medical School, USP, RibeirãoPreto, São Paulo, Brazil.
² Sport Sciences Course, Faculty of Applied Sciences, State University of Campinas, Limeira, São Paulo, Brazil.
³ Exercise Biochemistry and Physiology Laboratory Postgraduate Program in Health Sciences, Health Sciences Unit, University of Far Southern Santa Catarina, Criciúma, Santa Catarina, Brazil.
⁴ Postgraduate Program in Rehabilitation and Functional Performance, RibeirãoPreto Medical School, USP, RibeirãoPreto, São Paulo, Brazil; School of Physical Education and Sport of RibeirãoPreto, University of São Paulo, RibeirãoPreto, São Paulo, Brazil.

Abstract

The purpose of this study was to verify the effects of overtraining (OT) on insulin, inflammatory and gluconeogenesis signaling pathways in the livers of mice. Rodents were divided into control (CT), overtrained by downhill running (OTR/down), overtrained by uphill running (OTR/up) and overtrained by running without inclination (OTR). Rotarod, incremental load, exhaustive and grip force tests were used to evaluate performance. Thirty-six hours after a grip force test, the livers were extracted for subsequent protein analyses. The phosphorylation of insulin receptor beta (pIRbeta), glycogen synthase kinase 3 beta (pGSK3beta) and forkhead box O1 (pFoxo1) increased in OTR/down versus CT. pGSK3beta was higher in OTR/up versus CT, and pFoxo1 was higher in OTR/up and OTR versus CT. Phosphorylation of protein kinase B (pAkt) and insulin receptor substrate 1 (pIRS-1) were higher in OTR/up versus CT and OTR/down. The phosphorylation of IκB kinase alpha and beta (pIKKalpha/beta) was higher in all OT protocols versus CT, and the phosphorylation of stress-activated protein kinases/Jun amino-terminal kinases (pSAPK-JNK) was higher in OTR/down versus CT. Protein levels of peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha) and hepatocyte nuclear factor 4alpha (HNF-4alpha) were higher in OTR versus CT. In summary, OTR/down improved the major proteins of insulin signaling pathway but up-regulated TRB3, an Akt inhibitor, and its association with Akt.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Cycle Proteins / metabolism
Gluconeogenesis
Inflammation / metabolism*
Insulin / metabolism*
Liver / physiology*
Male
Mice
Mice, Inbred C57BL
Phosphorylation
Proto-Oncogene Proteins c-akt / metabolism
Receptor, Insulin / metabolism
Running*
Signal Transduction*

Substances

Cell Cycle Proteins
Insulin
TRB3 protein, mouse
Receptor, Insulin
Proto-Oncogene Proteins c-akt

Grants and funding

This work was supported by São Paulo Research Foundation: 2013/20591-3, ASRS; São Paulo Research Foundation: 2014/25459-9 and 2013/22737-5, ALR; and São Paulo Research Foundation: 2013/19985-7, BCP.