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Obesity represents a major health crisis in the United States, significantly increasing risks for chronic diseases and generating substantial economic costs. While bariatric surgery and pharmacological interventions such as GLP-1 receptor agonists have been proven effective in achieving substantial weight loss and improving comorbid conditions, they also raise concerns about the unintended loss of fat-free mass, particularly muscle. This loss of muscle mass compromises physical functionality, quality of life, and long-term metabolic health, particularly in individuals with sarcopenic obesity or those at risk of frailty. To sustain strength, mobility, and metabolic function during weight loss interventions, the preservation of muscle mass is essential. However, current weight-loss strategies often fail to adequately address the need to maintain fat-free mass. This review explores the physiological mechanisms governing muscle mass, the impact of obesity and rapid weight loss on muscle protein turnover, and nutritional and age-based strategies that may help protect muscle during intentional weight reduction. By focusing on these critical countermeasures, this review aims to inform future clinical practice and research initiatives with the long-term goal of achieving effective weight loss through reduction in fat tissue while preserving skeletal muscle mass, enhancing health outcomes, and long-term functionality in patients undergoing significant weight reduction.

Profound skeletal muscle wasting in the setting of total body hypermetabolism is a defining characteristic of massive burns, compromising the patient's recovery and necessitating a protracted period of rehabilitation. In recent years, the prolonged use of the non-selective beta-blocker, propranolol, has gained prominence as an effective tool to assist with suppressing epinephrine-dependent burn-induced hypermetabolism and by extension, blunting muscle catabolism. However, synthetic β-adrenergic agonists, such as clenbuterol, are widely associated with the promotion of muscle growth in both animals and humans. Moreover, experimental adrenodemedullation is known to result in muscle catabolism. Therefore, the blunting of muscle β-adrenergic signaling via the use of propranolol would be expected to negatively impair muscle protein homeostasis. This review explores these paradoxical observations and identifies the manner by which propranolol is thought to exert its anti-catabolic effects in burn patients. Moreover, we identify potential avenues by which the use of beta-blocker therapy in the treatment of massive burns could potentially be further refined to promote the recovery of muscle mass in these critically ill patients while continuing to ameliorate total body hypermetabolism., (Copyright © 2021 Elsevier Ltd and ISBI. All rights reserved.)

The contribution of myofibrillar protein synthesis (MyoPS) to recovery from skeletal muscle damage in humans is unknown. Recreationally active men and women consumed a daily protein-polyphenol beverage targeted at increasing amino acid availability and reducing inflammation (PPB; n = 9), both known to affect MyoPS, or an isocaloric placebo (PLA; n = 9) during 168 h of recovery from 300 maximal unilateral eccentric contractions (EE). Muscle function was assessed daily. Muscle biopsies were collected for 24, 27, 36, 72, and 168 h for MyoPS measurements using 2 H 2 O and expression of 224 genes using RT-qPCR and pathway analysis. PPB improved recovery of muscle function, which was impaired for 5 days after EE in PLA (interaction P < 0.05). Acute postprandial MyoPS rates were unaffected by nutritional intervention (24-27 h). EE increased overnight (27-36 h) MyoPS versus the control leg (PLA: 33 ± 19%; PPB: 79 ± 25%; leg P < 0.01), and PPB tended to increase this further (interaction P = 0.06). Daily MyoPS rates were greater with PPB between 72 and 168 h after EE, albeit after function had recovered. Inflammatory and regenerative signaling pathways were dramatically upregulated and clustered after EE but were unaffected by nutritional intervention. These results suggest that accelerated recovery from EE is not explained by elevated MyoPS or suppression of inflammation. NEW & NOTEWORTHY The present study investigated the contribution of myofibrillar protein synthesis (MyoPS) and associated gene signaling to recovery from 300 muscle-damaging, eccentric contractions. Measured with 2 H 2 O, MyoPS rates were elevated during recovery and observed alongside expression of inflammatory and regenerative signaling pathways. A nutritional intervention accelerated recovery; however, MyoPS and gene signaling were unchanged compared with placebo. These data indicate that MyoPS and associated signaling do not explain accelerated recovery from muscle damage.

The underlying aetiology of sarcopenia appears multifaceted and not yet fully defined, but ultimately involves the gradual loss of muscle protein content over time. The present evidence suggests that the loss of lean tissue in the elderly is exacerbated by low dietary protein intake. Moreover, acute stable-isotope-based methodologies have demonstrated that the muscle anabolic response to a given amount of protein may decline with age, a phenomenon that has been termed anabolic resistance. Although the mechanism responsible for the inability of muscle to mount a satisfactory anabolic response to protein provision with increasing age is presently unknown, it does not appear due to impaired digestion or absorption of dietary protein. Rather, the issue could reside with any combination of: a diminished delivery of amino acids to peripheral tissues, impaired uptake of amino acids into muscle cells, or an inability of amino acids to elicit intracellular events pivotal for anabolism to occur. Despite the presence of anabolic resistance to dietary protein, present evidence suggests that protein supplementation may be able to overcome these issues, particularly when combined with resistance exercise programmes. As such, protein supplementation may prove to be an effective approach to delay the loss of muscle mass with age and has led to calls for the recommended daily intake of protein to be increased for the elderly population.

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 ± 1.1 kg · m(-2)) and 15 healthy-weight (BMI 23.4 ± 0.3 kg · m(-2)) 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 hyperaminoacidemic-euglycemic 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., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

The ability to maintain skeletal muscle mass appears to be impaired in insulin-resistant conditions, such as type 2 diabetes, that are characterized by muscle lipid accumulation. The current study investigated the effect of acutely increasing lipid availability on muscle protein synthesis. Seven healthy young male volunteers underwent a 7-h intravenous infusion of l-[ring-(2)H5]phenylalanine on two randomized occasions combined with 0.9% saline or 10% Intralipid at 100 mL/h. After a 4-h "basal" period, a 21-g bolus of amino acids was administered and a 3-h hyperinsulinemic-euglycemic clamp was commenced ("fed" period). Muscle biopsy specimens were obtained from the vastus lateralis at 1.5, 4, and 7 h. Lipid infusion reduced fed whole-body glucose disposal by 20%. Furthermore, whereas the mixed muscle fractional synthetic rate increased from the basal to the fed period during saline infusion by 2.2-fold, no change occurred during lipid infusion, despite similar circulating insulin and leucine concentrations. This "anabolic resistance" to insulin and amino acids with lipid infusion was associated with a complete suppression of muscle 4E-BP1 phosphorylation. We propose that increased muscle lipid availability may contribute to anabolic resistance in insulin-resistant conditions by impairing translation initiation., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Purpose of Review: Therapeutic exercise may help maintain or slow down the rate of decline in muscle mass and physical function that occurs with cachexia. This review considers recent evidence in relation to patients with cachexia as regards the rationale for the use of exercise, the challenges in its clinical application and future developments., Recent Findings: Exercise may attenuate the effects of cachexia by modulating muscle metabolism, insulin sensitivity and levels of inflammation. Studies targeting cachectic patients have demonstrated that even in advanced disease peripheral muscle has the capacity to respond to exercise training. Nonetheless, there are challenges in implementing the use of exercise, particularly once cachexia is established in which tolerance to even low levels of exercise is poor. Strategies to make exercise a more accessible therapy are required and could include offering exercise earlier on in the course of the disease, at lower intensities and in various forms, including more novel approaches., Summary: The use of therapeutic exercise has a sound rationale, even in patients with advanced disease and cachexia. Because of practical issues with its application, further study is required to examine if benefits achieved in small studies can be translated to a wider clinical population.

Muscle mass loss accompanies periods of bedrest and limb immobilization in humans and requires rehabilitation exercise to effectively restore mass and function. Although recent evidence points to an early and transient rise in muscle protein breakdown contributing to this decline in muscle mass, the driving factor seems to be a reduction in muscle protein synthesis, not least in part due to the development of anabolic resistance to amino acid provision. Although the AKT signaling pathway has been identified in small animals as central to the regulation of muscle protein synthesis, several studies in humans have now demonstrated a disassociation between AKT signaling and muscle protein synthesis during feeding, exercise, and immobilization, suggesting that the mechanisms regulating protein synthesis in human skeletal muscle are more complex than initially thought (at least in non-inflammatory states). During rehabilitation, exercise-induced myogenesis may in part be responsible for the recovery of muscle mass. Rapid and sustained exercise-induced suppression of myostatin mRNA expression, that precedes any gain in muscle mass, points to this, along with other myogenic proteins, as being potential regulators of muscle regeneration during exercise rehabilitation in humans.

Purpose of Review: The preservation of skeletal muscle mass is central to maintaining mobility and quality of life with aging and also impacts on our capacity to recover from illness. However, our understanding of the processes that regulate muscle mass in humans during exercise, chronic disuse and rehabilitation remains unclear. This brief review aims to highlight some of the more recent and important findings concerning these physiological stimuli., Recent Findings: Although several studies have detailed the molecular events that occur following an acute bout of resistance exercise, a paucity of data appears to remain concerning the molecular and signaling events that underpin resistance exercise training. Reports of increased transcripts for inflammatory proteins following eccentric but not concentric exercise could represent the stimulus for the instigation of structural adaptations that occur following intense muscle lengthening contractions. Studies investigating processes underlying disuse-induced muscle atrophy provide initial evidence to support the notion that transient increases in muscle protein degradation occur following the onset of muscle disuse in humans., Summary: The need for further studies to improve our basic understanding of muscle-associated processes in humans remains, particularly in relation to the temporal changes in muscle processes that occur during resistance training.

Purpose of Review: Recent reports exploring the mechanisms thought to be responsible for the determination of muscle mass during health, ageing and immobilization in humans have presented findings that have wide ranging implications. This brief review highlights some of the more important findings., Recent Findings: Contrary to expectations, recent findings suggest an apparent dissociation between muscle signalling pathways and their associated events in humans, particularly in relation to muscle protein synthesis. Although debate concerning the relative importance of muscle protein synthesis and degradation to muscle mass loss during immobilization continues, and the mechanisms responsible for this loss and its restoration during rehabilitation remain unclear, new evidence has emerged showing that anabolic resistance to protein nutrition develops during immobilization. This latter observation is in agreement with earlier evidence pointing to anabolic resistance of muscle to protein nutrition existing in the elderly, which is of clinical importance. Recent observations also suggest that a sex difference exists in the rate of muscle protein synthesis under postabsorptive conditions in the elderly and may explain why women lose muscle mass at a slower rate with age than men., Summary: These recent findings highlight our current lack of understanding of the mechanisms that regulate muscle mass in humans.