Age-Related Anabolic Resistance of Myofibrillar Protein Synthesis Is Exacerbated in Obese Inactive Individuals

Abstract

Context:A diminished muscle anabolic response to protein nutrition may underpin age-associated muscle loss.Objective:To determine how chronological and biological aging influence myofibrillar protein synthesis (MyoPS).Design:Cross-sectional comparison.Setting:Clinical research facility.Participants:Ten older lean [OL: 71.7 ± 6 years; body mass index (BMI) ≤25 kg ⋅ m−2], 7 older obese (OO: 69.1 ± 2 years; BMI ≥30 kg ⋅ m−2), and 18 young lean (YL) individuals (25.5 ± 4 years; BMI ≤25 kg ⋅ m−2).Intervention:Skeletal muscle biopsies obtained during a primed-continuous infusion of l-[ring-13C6]-phenylalanine.Main Outcome Measures:Anthropometrics, insulin resistance, inflammatory markers, habitual diet, physical activity, MyoPS rates, and fiber-type characteristics.Results:Fat mass, insulin resistance, inflammation, and type II fiber intramyocellular lipid were greater, and daily step count lower, in OO compared with YL and OL. Postprandial MyoPS rates rose above postabsorptive values by ∼81% in YL (P < 0.001), ∼38% in OL (P = 0.002, not different from YL), and ∼9% in OO (P = 0.11). Delta change in postprandial MyoPS from postabsorptive values was greater in YL compared with OL (P = 0.032) and OO (P < 0.001). Absolute postprandial MyoPS rates and delta postprandial MyoPS change were associated with step count (r2 = 0.33; P = 0.015) and leg fat mass (r2 = 0.4; P = 0.006), respectively, in older individuals. Paradoxically, lean mass was similar between groups, and muscle fiber area was greater in OO vs OL (P = 0.002).Conclusion:Age-related muscle anabolic resistance is exacerbated in obese inactive individuals, with no apparent detriment to muscle mass.

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

“…; Smeuninx et al . ). Interestingly, it appears that this anabolic resistance of postprandial muscle protein synthesis rates in response to exogenous amino acid administration may be confined to distinct muscle protein subfractions (Guillet et al .…”

“…insulin resistance) (Bajpeyi et al 2011). Specifically, several studies have reported a reduced stimulation of the muscle protein synthetic response to amino acid provision in obese adults compared to normal weight controls (Guillet et al 2009;Chevalier et al 2015;Murton et al 2015;Beals et al 2016;Smeuninx et al 2017). Interestingly, it appears that this anabolic resistance of postprandial muscle protein synthesis rates in response to exogenous amino acid administration may be confined to distinct muscle protein subfractions (Guillet et al 2009;Chevalier et al 2015;Murton et al 2015;Beals et al 2016Beals et al , 2017.…”

Sarcopenic Obesity: Time to Meet the Challenge

“…Indeed a positive association between BMI and lean body mass has been reported in general population studies [23], and moderate increments in skeletal muscle mass may occur in obesity as a consequence of higher postural and ambulatory muscle work as well as potential direct anabolic effects of higher dietary intake of calorie proteins. It is however increasingly clear that profound skeletal muscle metabolism changes may occur in obesity and may lead to altered body composition with higher fat mass and substantial impairment of muscle mass and quality [24,25,26,27]. Various complex interrelated mechanisms may contribute to these changes.…”

“…These alterations are at least in part causally interrelated and have a strong muscle-catabolic potential [31]; they can also promote a typical ‘anabolic resistance' state in skeletal muscle, meaning that the response of muscle protein synthesis to nutrients is blunted [24,25,26,27]. …”

“…While these changes are not inevitable, they become increasingly likely in patients with longer obesity duration, complications, and comorbidities as well as in elderly individuals that may undergo muscle changes also due to aging per se [52]. Most mechanisms directly reduce muscle anabolism, thereby reducing muscle mass as previously described [24,25,26,27]. In addition, several alterations have a negative impact on muscle quality in terms of strength per muscle unit and endurance capacity.…”