Altered anabolic signalling and reduced stimulation of myofibrillar protein synthesis after feeding and resistance exercise in people with obesity

Abstract

We aimed to determine whether obesity alters muscle anabolic and inflammatory signalling phosphorylation and also muscle protein synthesis within the myofibrillar (MYO) and sarcoplasmic (SARC) protein fractions after resistance exercise. Nine normal weight (NW) (21 ± 1 years, body mass index 22 ± 1 kg m ) and nine obese (OB) (22 ± 1 years, body mass index 36 ± 2 kg m ) adults received l-[ring- C ]phenylalanine infusions with blood and muscle sampling at basal and fed-state of the exercise (EX) and non-exercise (CON) legs. Participants performed unilateral leg extensions and consumed pork (36 g of protein) immediately after exercise. Basal muscle Toll-like receptor 4 (TLR4) protein was similar between OB and NW groups (P > 0.05) but increased at 300 min after pork ingestion only in the OB group (P = 0.03). Resistance exercise reduced TLR4 protein in the OB group at 300 min (EX vs. CON leg in OB: P = 0.04). Pork ingestion increased p70S6K phosphorylation at 300 min in CON and EX of the OB and NW groups (P > 0.05), although the response was lower in the EX leg of OB vs. NW at 300 min (P = 0.05). Basal MYO was similar between the NW and OB groups (P > 0.05) and was stimulated by pork ingestion in the EX and CON legs in both groups (Δ from basal NW: CON 0.04 ± 0.01% h ; EX 0.10 ± 0.02% h ; OB: CON 0.06 ± 0.01% h ; EX 0.06 ± 0.01% h ; P < 0.05). MYO was more strongly stimulated in the EX vs. CON legs in NW (P = 0.02) but not OB (P = 0.26). SARC was feeding sensitive but not further potentiated by resistance exercise in both groups. Our results suggest that obesity may attenuate the effectiveness of resistance exercise to augment fed-state MYO.

When bigger isn't better: understanding the anabolic resistance of obese skeletal muscle

“…Recently, Beals and colleagues () published a formative paper in The Journal of Physiology that aimed to clarify the degree to which anabolic resistance may be present in obese individuals in response to two potent anabolic stimuli: dietary protein ingestion and resistance exercise (RE). As females are consistently underrepresented in the exercise science literature, the inclusion of both sedentary, normal‐weight (NW; ∼23% body fat, ∼47.8 kg LBM) and obese (OB; ∼37% body fat, ∼63.2 kg LBM) male and female participants represented a strength of the study that, despite potentially being underpowered for sex‐based comparisons, arguably increases the ecological validity of the study results.…”

“…), it would be intriguing to determine if intramuscular fat depots of OB may physically and/or biochemically interfere with the sarcolemmal targeting of mTORC1 and, thus, its kinase activity. Therefore, while traditional Western blot techniques such as those used by Beals and colleagues () have long been used to estimate mTOR pathway activation, important mechanistic insights that can only be observed looking at cellular localization of signalling molecules may be missed. Thus, it is unclear to what extent dysregulated translocation events may have contributed to the blunted myoPS in OB muscle and this would represent a fruitful area of future study.…”

“…Beals and colleagues () hypothesized that this population may have an attenuated training‐induced increase in muscle hypertrophy due to the blunted acute myoPS response observed. However, previous work has found that myoPS is elevated for up to 48 h in healthy young men (Damas et al .…”

“…). Therefore, although Beals and colleagues () provide valuable insight into the acute response to a novel RE bout, future work investigating the habituated response to RE (i.e. after > 3 weeks of training) may remove potential confounding influences and provide a more comprehensive examination of skeletal muscle remodelling in clinical populations.…”

“…If left unmanaged, this dysfunctional process could have deleterious effects as one ages. Therefore, the study by Beals and associates () paves the way for the investigation into the mechanistic underpinnings of skeletal muscle metabolic dysregulation, and for future research to help determine how to make a ‘bigger’ muscle also a ‘better’ muscle.…”