Resistance training regulates gene expression of molecules associated with intramyocellular lipids, glucose signaling and fiber size in old rats

Abstract

Sarcopenia is a complex multifactorial process, some of which involves fat infiltration. Intramyocellular lipid (IMCL) accumulation is postulated to play a role on sarcopenia during aging, which is believed to be due alterations in glucose homeostasis in the skeletal muscle. Sarcopenia, along with intramuscular lipids, is associated with physical inactivity. Resistance training (RT) has been indicated to minimize the age-induced muscle skeletal adaptations. Thus, we aimed to investigate the effects of RT on mRNA levels of regulatory components related to intramyocellular lipid, glucose metabolism and fiber size in soleus and gastrocnemius muscles of aged rats. Old male rats were submitted to RT (ladder climbing, progressive load, 3 times a week for 12 weeks). Age-induced accumulation of IMCL was attenuated by RT, which was linked to a PPARy-mediated mechanism, concomitant to enhanced regulatory components of glucose homeostasis (GLUT-4, G6PDH, Hk-2 and Gly-Syn-1). These responses were also linked to decreased catabolic (TNF-α, TWEAK/Fn14 axis; FOXO-1, Atrogin-1 and MuRF1; Myostatin) and increased anabolic intracellular pathways (IGF-1-mTOR-p70S6sk-1 axis; MyoD) in muscles of trained aged rats. Our results point out the importance of RT on modulation of gene expression of intracellular regulators related to age-induced morphological and metabolic adaptations in skeletal muscle.

Muscle hypertrophy and ladder‐based resistance training for rodents: A systematic review and meta‐analysis

“…Rodent sample number per group varied from 4 to 18 rats. Twenty‐three articles described the rat's initial body mass (Antonio‐Santos et al., 2016; Cassilhas et al., 2013; Deus et al., 2012; Deschenes et al., 1994; Deschenes, Sherman, Roby, Glass, & Harris, 2015; Domingos et al., 2012; Gil & Kim, 2015; Grans et al., 2014; Hornberger & Farrar, 2004; Jung et al., 2015; Krause Neto & Gama, 2017; Lee, Hong, & Kim, 2016; Mônico‐Neto et al, 2015; Nascimento et al., 2013; Neves et al, 2019; Padilha et al, 2017; Padilha et al., 2019; Prestes et al, 2009, 2012; Ribeiro et al, 2017; Shamsi et al, 2013; Souza et al., 2014; Tibana et al, 2017). Ladder‐based equipment structure varied from 1–1.3 m of height and 70–90° of inclination between studies.…”

“…The muscles included in the selected articles were quadriceps femoris (Luciano et al, 2017; Neves et al, 2019), soleus (Cassilhas et al., 2013; Deschenes et al., 1994, 2000, 2015; Grans et al., 2014; Krause Neto & Gama, 2017; Padilha et al, 2017; Padilha et al., 2019; Prestes et al, 2012; Ribeiro et al, 2017; Shamsi et al, 2013), tibialis anterior [TA] (Jung et al., 2015; Lee et al, 2016; Neves et al, 2019; Prestes et al, 2012), gastrocnemius (Cassilhas et al., 2013; Grans et al., 2014; Lee et al, 2016; Ribeiro et al, 2017; Souza et al., 2014; Tibana et al, 2017), plantaris (Cassilhas et al., 2013; Deschenes et al., 2015; Mônico‐Neto et al, 2015; Padilha et al., 2019), FHL (Chi, Hou, Wu, Wang, & Yu, 2020; Gil & Kim, 2015; Hornberger & Farrar, 2004; Lee et al, 2016, 2018; Lee & Farrar, 2003; Padilha et al., 2019; Shamsi et al, 2014), extensor digitorum longus [EDL] (Deschenes et al., 1994; Krause Neto & Gama, 2017; Lim et al, 2018), flexor digitorum profundus [FDP] (Chi et al., 2020; Kwon et al, 2018), flexor digitorum longus [FDL] (Cassilhas et al., 2013), tríceps brachialis (Nascimento et al., 2013) and bíceps brachialis (Souza et al., 2014).…”

“…According to Tibana et al (2017), despite no increased muscle mass, LRT is efficient in inducing a significant increase in the mean muscle fibers cross‐sectional area (fCSA) and the capacity of the rodent to carry the load. Yet, other studies corroborate these conclusions, demonstrating that LRT might stimulate hypertrophy of several different types of muscles (Jung et al., 2015; Know, Jang, Cho, Jang, & Lee, 2017; Lim, Gil, Quan, Viet, & Kim, 2018; Luciano et al, 2017; Ribeiro et al, 2017).…”

Cellular and molecular mechanisms of sarcopenia: the S100B perspective

“…A minority of proliferating myoblasts return to a state of quiescence to replenish the SC reserve pool. 42 Defective activity or abundance of Nrf2, an antioxidant factor playing a fundamental role in the maintenance of intracellular redox homeostasis, characterizes the aging muscle tissue (reviewed by Bellezza et al 43 ), an event counteracted by a regular exercise that attenuates the age-related changes in Nrf2-mediated pathways and potentially restores the redox homeostasis 28,[44][45][46] (Figure 2). Pericytes and IL-4-activated FAPs also participate in the regeneration process.…”

“…25 Yet a ROS-FoxO cross-talk occurs in cells whereby ROS and FoxO reciprocally regulate their levels, 40,41 and old sedentary rat muscles show elevated levels of the atrophy genes (atrogenes), atrogin-1 and MuRF-1. 42 Defective activity or abundance of Nrf2, an antioxidant factor playing a fundamental role in the maintenance of intracellular redox homeostasis, characterizes the aging muscle tissue (reviewed by Bellezza et al 43 ), an event counteracted by a regular exercise that attenuates the age-related changes in Nrf2-mediated pathways and potentially restores the redox homeostasis 28,[44][45][46] (Figure 2). Supporting this possibility is the observation that the Nrf2 activator, sulforaphane, enhances running capacity in rats by up-regulation of Nrf2 signalling and downstream genes and attenuates muscle fatigue via reduction of oxidative stress caused by exhaustive exercise.…”