Obesity Appears to Be Associated With Altered Muscle Protein Synthetic and Breakdown Responses to Increased Nutrient Delivery in Older Men, but Not Reduced Muscle Mass or Contractile Function

Abstract

Obesity is increasing, yet despite the necessity of maintaining muscle mass and function with age, the effect of obesity on muscle protein turnover in older adults remains unknown. Eleven obese (BMI 31.9 6 1.1 kg $ m 22) and 15 healthy-weight (BMI 23.4 6 0.3 kg $ m 22) older men (55-75 years old) participated in a study that determined muscle protein synthesis (MPS) and leg protein breakdown (LPB) under postabsorptive (hypoinsulinemic-euglycemic clamp) and postprandial (hyperinsulinemic hyperaminoacidemiceuglycemic clamp) conditions. Obesity was associated with systemic inflammation, greater leg fat mass, and patterns of mRNA expression consistent with muscle deconditioning, whereas leg lean mass, strength, and work done during maximal exercise were no different. Under postabsorptive conditions, MPS and LPB were equivalent between groups, whereas insulin and amino acid administration increased MPS in only healthy-weight subjects and was associated with lower leg glucose disposal (LGD) (63%) in obese men. Blunting of MPS in the obese men was offset by an apparent decline in LPB, which was absent in healthy-weight subjects. Lower postprandial LGD in obese subjects and blunting of MPS responses to amino acids suggest that obesity in older adults is associated with diminished muscle metabolic quality. This does not, however, appear to be associated with lower leg lean mass or strength.

Differential regulation of lipid and protein metabolism in obese vs. lean subjects before and after a 72-h fast

“…A recent study compared leg muscle protein metabolism in older obese and lean subjects under highly complex metabolic conditions of insulin, glucagon, and somatostatin administration and found similar indices of protein synthesis and breakdown and intramyocellular protein metabolic signaling in the two groups (19). The discrepancy with our results could relate to the metabolic complexity of the setup altering the concentrations of protein metabolic hormones such as insulin, glucagon, and growth hormone.…”

Obesity is associated with insulin resistance but not skeletal muscle dysfunction or all-cause mortality

“…This finding, which necessitates replication, suggests that the maintenance of lean mass and strength may contribute to this obesity paradox, which suggests that obesity may provide a survival benefit under certain situations (Hainer and Aldhoon-Hainerova 2013). Our finding that the obese were associated with greater lean mass and strength is in agreement with previous research and is thought to be the result of the added mechanical work performed by the obese during activities of daily living (James et al 1978;Murton et al 2015). Although some have suggested that this obesity paradox is specific to men (Mohebi et al 2015;Migaj et al 2015), we observed no sex differences with this effect.…”

“…This analysis was modeled on a recent study that suggested that lean body mass and strength was not decreased in the obese compared to the healthy weight group, despite having a blunting of muscle protein synthesis in response to amino acids and a lower disposal of glucose (Murton et al 2015). One limitation noted by the authors was that they were unable to account for the influence of daily physical activity, although they noted that Bovert traits of muscle deconditioning were evident in the obese volunteers.^We provide epidemiological Fig.…”

“…Skeletal muscle is highly plastic and is capable of responding to a variety of stimuli, however, some data suggests that obesity may alter the anabolic response through chronic inflammation and insulin resistance (Barzilay et al 2001;Schaap et al 2006;Yudkin et al 1999). Recently, a study among 11 obese and 15 healthy weight older males found that obese men with chronic inflammation had a blunting of muscle protein synthesis but that this was offset by a decrease in leg protein breakdown (Murton et al 2015). In support of this, they found similar levels of leg lean mass and strength between those who were obese and of a healthy bodyweight.…”

Acute cocoa flavanol supplementation improves muscle macro- and microvascular but not anabolic responses to amino acids in older men

“…Such anabolic resistance has not only been conjectured by us and others to contribute to the sarcopenia of ageing but it also appears to be a common feature of many kinds of muscle atrophy (e.g. with immobilization (Glover et al 2008), reduced physical activity (Breen et al 2013), heart failure (Toth et al 2010), obesity (Guillet et al 2009;Murton et al 2015) and cancer ), suggesting a final common pathway for a variety of insults resulting in diminished anabolism. Whereas the regulatory mechanisms of anabolic resistance remain poorly defined, possible links between reduced muscle MBF and diminished anabolic responses to plasma nutrient availability may be a general feature of a number of conditions.…”