Exercise Mitigates the Loss of Muscle Mass by Attenuating the Activation of Autophagy during Severe Energy Deficit

Abstract

The loss of skeletal muscle mass with energy deficit is thought to be due to protein breakdown by the autophagy-lysosome and the ubiquitin-proteasome systems. We studied the main signaling pathways through which exercise can attenuate the loss of muscle mass during severe energy deficit (5500 kcal/day). Overweight men followed four days of caloric restriction (3.2 kcal/kg body weight day) and prolonged exercise (45 min of one-arm cranking and 8 h walking/day), and three days of control diet and restricted exercise, with an intra-subject design including biopsies from muscles submitted to distinct exercise volumes. Gene expression and signaling data indicate that the main catabolic pathway activated during severe energy deficit in skeletal muscle is the autophagy-lysosome pathway, without apparent activation of the ubiquitin-proteasome pathway. Markers of autophagy induction and flux were reduced by exercise primarily in the muscle submitted to an exceptional exercise volume. Changes in signaling are associated with those in circulating cortisol, testosterone, cortisol/testosterone ratio, insulin, BCAA, and leucine. We conclude that exercise mitigates the loss of muscle mass by attenuating autophagy activation, blunting the phosphorylation of AMPK/ULK1/Beclin1, and leading to p62/SQSTM1 accumulation. This includes the possibility of inhibiting autophagy as a mechanism to counteract muscle loss in humans under severe energy deficit.

No effect of increasing protein intake during military exercise with severe energy deficit on body composition and performance

“…Surprisingly, neither HIGH nor LOW displayed changes in FFM in response to the military exercise, despite substantial impairment in muscle performance. This suggests that the amount of muscle mass was unaffected by the intervention, which contrasts findings in most previous studies, 1,2,6,7,9,36,37 some of which even involved similar 36,37 or less severe energy deficit and shorter duration compared to the present study. 7,9,36,37 Conversely, our perspective data are supported by Tanskanen et al, 5 wherein 8 days of military exercise did not lead to decreases in FFM, though also in that study the intervention involved less severe energy deficit (<50%) and higher energy intake and had shorter duration.…”

The P2X7 Receptor in Osteoarthritis

“…In skeletal muscle, exercise induces mitophagy to degrade damaged mitochondria through the AMPK-Ulk1 signaling pathway ( Laker et al, 2017 ). When energy is severely lacking, exercise inhibits AMPK/Ulk1/Beclin-1 phosphorylation, and the accumulated p62/SQATM1 inhibits autophagy to reduce muscle loss ( Martin-Rincon et al, 2019 ). As an important downstream signaling molecule of P2X7R, AMPK is involved in the regulation of several physiological and pathological functions ( Jeon, 2016 ), including autophagy in OA.…”

Can Exercise-Induced Muscle Damage Be a Good Model for the Investigation of the Anti-Inflammatory Properties of Diet in Humans?

“…According to the extent of muscle damage, RONS can further damage the muscle tissue but they also play a significant role for muscle regeneration and the adaptation of muscle tissues to eccentric exercise by mediating the up-regulation of antioxidant enzymes and the mitohormetic effects of exercise [ 14 , 16 , 18 , 70 , 79 , 120 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 ]. As a consequence of the activation of all the previous mentioned mechanisms in response to EIMD muscle cells’ autophagy, apoptosis, and regeneration-adaptation molecular mechanisms are upregulated, to reinforce the regeneration of muscle cells [ 103 , 136 , 141 , 144 , 146 , 148 , 152 , 153 , 154 , 155 , 156 , 157 , 158 , 159 , 160 , 161 , 162 , 163 , 164 , 165 , 166 , 167 , 168 , 169 ,…”

“…For example, the inflammatory status of certain population groups (e.g., obese vs. normal weight) can be better assessed and compared under the dynamic conditions of EIMD. Taking into account that muscle biopsies can also be obtained and then the molecular mechanisms of autophagy, apoptosis and regeneration-adaptation could also be studied [ 75 , 103 , 136 , 141 , 144 , 146 , 148 , 152 , 153 , 154 , 155 , 156 , 157 , 158 , 159 , 160 , 161 , 162 , 163 , 164 , 165 , 166 , 167 , 168 , 169 , 170 , 171 , 172 , 173 , 174 , 175 , 176 , 177 , 178 , 179 , 180 , 181 , 182 ]. Considering the pathophysiology behind conditions such as muscle/neurogenic inflammation, atrophy, cachexia, sarcopenia, and chronic muscle protein degradation EIMD can serve as a very reliable and regulated model to investigate how nutrition and or exercise may affect the physiological and biochemical background of those conditions.…”