Pereira, Marcelo G.
Voltarelli, Vanessa A.
[1, 3, 4]
Tobias, Gabriel C.
[1, 5, 6]
de Souza, Lara
Borges, Gabriela S.
Paixao, Ailma O.
de Almeida, Ney R.
Bowen, Thomas Scott
Miyabara, Elen H.
Brum, Patricia C.
Total Authors: 11
 Univ Sao Paulo, Sch Phys Educ & Sport, BR-05508030 Sao Paulo - Brazil
 Univ Leeds, Fac Biol Sci, Leeds Sch Biomed Sci, Leeds LS2 9JT, W Yorkshire - England
 Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02115 - USA
 Siriolibanes Hosp, BR-01308050 Sao Paulo - Brazil
 Weill Cornell Med, Meyer Canc Ctr, Childrens Canc & Blood Fdn Labs, Drukier Inst Childrens Hlth, Dept Pediat, New York, NY 10021 - USA
 Weill Cornell Med, Meyer Canc Ctr, Childrens Canc & Blood Fdn Labs, Drukier Inst Childrens Hlth, Dept Cell & Dev Biol, New York, NY 10021 - USA
 Butantan Inst, Biochem & Biophys Lab, BR-05503900 Sao Paulo - Brazil
 Univ Sao Paulo, Inst Biomed Sci, Dept Anat, BR-05508000 Sao Paulo - Brazil
Total Affiliations: 8
Web of Science Citations:
Simple Summary:\& nbsp;Chronic disease-related muscle atrophy is a serious public health problem since it reduces mobility and contributes to increases in hospitalization costs. Unfortunately, there is no approved treatment for muscle wasting at present. Thus, an understanding of the mechanisms underlying the control of muscle mass and function under chronic diseases can pave the way for the discovery of innovative therapeutic strategies to counteract muscle wasting. Since numerous types of cancer induce cachexia, which has no cure nor an effective treatment, the main proposal here was to study the effects of AET in cancer cachexia, and to investigate, through in vivo manipulation of the Akt/mTORC1 pathway, whether the cachectic muscle still presents conditions to respond adaptively to hypertrophic stimuli. Our results could provide a basis for innovative research lines to better understand muscle plasticity and to investigate potential therapeutic approaches necessary to prevent muscle loss.\& nbsp;Cancer cachexia is a multifactorial and devastating syndrome characterized by severe skeletal muscle mass loss and dysfunction. As cachexia still has neither a cure nor an effective treatment, better understanding of skeletal muscle plasticity in the context of cancer is of great importance. Although aerobic exercise training (AET) has been shown as an important complementary therapy for chronic diseases and associated comorbidities, the impact of AET on skeletal muscle mass maintenance during cancer progression has not been well documented yet. Here, we show that previous AET induced a protective mechanism against tumor-induced muscle wasting by modulating the Akt/mTORC1 signaling and eukaryotic initiation factors, specifically eIF2-alpha. Thereafter, it was determined whether the in vivo Akt activation would induce a hypertrophic profile in cachectic muscles. As observed for the first time, Akt-induced hypertrophy was able and sufficient to either prevent or revert cancer cachexia by modulating both Akt/mTORC1 pathway and the eIF-2 alpha activation, and induced a better muscle functionality. These findings provide evidence that skeletal muscle tissue still preserves hypertrophic potential to be stimulated by either AET or gene therapy to counteract cancer cachexia. (AU)