Abstract
This study investigated the effects of long-term physical inactivity in adolescent on subsequent hindlimb unloading-induced muscle atrophy in rat soleus muscle. First, 3-wk-old male Wistar rats were assigned to an age-matched control (n = 6) or a physical inactivity (n = 8) group. Rats in the physical inactivity group were housed in narrow cages with approximately half the usual floor space for 8 wk to limit range of movement. Whole body energy consumption was measured, and the blood, organs, femoral bone, and hindlimb muscles were removed. We found that long-term physical inactivity did not affect the metabolic and physiological characteristics of growing rats. Then, fifty-six 3-wk-old male Wistar rats were assigned randomly into control (n = 28) and physical inactivity (n = 28) groups. After 8 wk, the rats in both groups underwent hindlimb unloading. The soleus muscles were removed before unloading (0 day), and 1, 3, and 7 days after unloading (n = 7 for each). Although the soleus muscle weight was significantly decreased after 7 days of hindlimb unloading in both groups, the decrease was drastic in the inactive group. A significant interaction between inactivity and unloading (P < 0.01) was observed according to the 4-hydroxynonenal-conjugated protein levels and the histone deacetylase 4 (HDAC4) and NF-κB protein levels. HDAC4 and NF-κB p65 protein levels in the physical inactivity group increased significantly 1 day after hindlimb unloading, along with the mRNA levels of their downstream targets myogenin and muscle RING finger protein 1 (MuRF1). Subsequent protein ubiquitination was upregulated by long-term physical inactivity (P < 0.05).NEW & NOTEWORTHY Long-term physical inactivity exacerbates hindlimb unloading-induced disuse muscle atrophy in young rat soleus muscles, possibly mediated by oxidative stress-induced protein ubiquitination via HDAC4- and NF-κB p65-induced MuRF1 mRNA upregulation.
Highlights
In the past decade, physical inactivity has been recognized as a risk factor for morbidity and mortality due to cardiovascular diseases, cancer, chronic respiratory diseases, and diabetes worldwide [1, 2]
We examined the potential effects of 8 wk of physical inactivity during adolescence on the metabolic and physiological characteristics and whether long-term physical inactivity exacerbates subsequent hindlimb-induced antigravity muscle atrophy in rat soleus muscle
We investigated the potential effects of 8 wk of physical inactivity during adolescence on the metabolic and physiological characteristics of growing rats, and whether long-term physical inactivity during adolescence exacerbates subsequent hindlimb-induced antigravity muscle atrophy in rat soleus muscle
Summary
Physical inactivity (sedentary lifestyle) has been recognized as a risk factor for morbidity and mortality due to cardiovascular diseases, cancer, chronic respiratory diseases, and diabetes worldwide [1, 2]. Even 2 wk of reduced daily step count by $76% (1,400 steps) induced a significant decline in leg fat-free mass ($3.9%) and is accompanied with impairment of insulin sensitivity, systemic inflammatory makers, and myofibrillar protein synthesis in healthy elderly adults [11]. McGlory et al [12] demonstrated that 2 wk of reduced activity ($7,300 steps to 990 steps) lowered integrated muscle protein synthesis and insulin sensitivity in overweight and prediabetic older adults. The maintenance of skeletal muscle mass is necessary to LicenDsoewd nulnodaedreCdrefraotimvejoCuormnmalos.npshAysttiroiblougtioyn.oCrgC/j-BouYr4n.a0l./jPaupbpllis(h0e3d5.b1y7t2h.e11A9m.1e1ri7c)anonPhNyosivoelomgbicearl8S,o2c0ie2t1y
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