α-Hydroxyisocaproic Acid Decreases Protein Synthesis but Attenuates TNFα/IFNγ Co-Exposure-Induced Protein Degradation and Myotube Atrophy via Suppression of iNOS and IL-6 in Murine C2C12 Myotube

There is ongoing debate as to whether or not α-hydroxyisocaproic acid (HICA) positively regulates skeletal muscle protein synthesis resulting in the gain or maintenance of skeletal muscle. We investigated the effects of HICA on mouse C2C12 myotubes under normal conditions and during cachexia induced by co-exposure to TNFα and IFNγ. The phosphorylation of AMPK or ERK1/2 was significantly altered 30 min after HICA treatment under normal conditions. The basal protein synthesis rates measured by a deuterium-labeling method were significantly lowered by the HICA treatment under normal and cachexic conditions. Conversely, myotube atrophy induced by TNFα/IFNγ co-exposure was significantly improved by the HICA pretreatment, and this improvement was accompanied by the inhibition of iNOS expression and IL-6 production. Moreover, HICA also suppressed the TNFα/IFNγ co-exposure-induced secretion of 3-methylhistidine. These results demonstrated that HICA decreases basal protein synthesis under normal or cachexic conditions; however, HICA might attenuate skeletal muscle atrophy via maintaining a low level of protein degradation under cachexic conditions.

A Moderate Serving of a Lower-Quality, Incomplete Protein Does Not Stimulate Skeletal Muscle Protein Synthesis

Objectives Dietary proteins can be broadly characterized by their origin (animal-or plant-based) and amino acid composition (complete vs. incomplete). Meals containing > 20 g of high-quality, complete protein have repeatedly been shown to robustly stimulate skeletal muscle protein synthesis. However, breakfast in many Western countries is dominated by wheat-based products. Wheat and bread are considered a “lower-quality” incomplete source of protein, containing relatively low amounts of lysine and threonine. We hypothesized that a meal containing > 20 g of wheat-based protein would offer no anabolic advantage over a control meal containing only 5 g of plant-based protein. Methods In a subset of healthy, middle-aged women from our recently completed trial (n = 6/17, 53 ± 7 y, 27 ± 2 kg/m2), we measured post-prandial skeletal muscle protein synthesis, blood glucose, insulin and appetite for 3 h following the ingestion of: i) a wheat-based protein meal (INCOMPLETE: 717 kcal, 23 g protein, 120 g carbohydrate, 16 g fat) or ii) a low protein, plant-based, control meal (CONTROL: 542 kcal, 5 g protein, 86 g carbohydrate and 23 g fat). Venous blood samples and vastus lateralis muscle biopsy samples were obtained during a primed (2.0 mmol/kg) constant infusion (0.08 mmol/(kg/min)) of L-[ring-13C6]phenylalanine. All analyses were performed using established, standard techniques. Results Preliminary results indicate post-prandial skeletal muscle protein synthesis was similar in both cohorts (INCOMPLETE: 0.050 ± 0.012%/h vs. CONTROL: 0.054 ± 0.025%/h; p = 0.83) and consistent with fasting values historically measured by our lab. Blood glucose area under the curve (AUC; p = 0.82), insulin AUC (p = 0.85) and hunger AUC were similar in both cohorts. Conclusions A moderate serving of incomplete protein failed to robustly stimulate skeletal muscle protein synthesis. Consumption of a higher-quality, completeprotein meal is likely required to acutely increase muscle protein anabolism. Funding Sources National Cattlemen's Beef Association

Amino Acid Trafficking and Skeletal Muscle Protein Synthesis: A Case of Supply and Demand

Skeletal muscle protein synthesis is a highly complex process, influenced by nutritional status, mechanical stimuli, repair programs, hormones, and growth factors. The molecular aspects of protein synthesis are centered around the mTORC1 complex. However, the intricacies of mTORC1 regulation, both up and downstream, have expanded overtime. Moreover, the plastic nature of skeletal muscle makes it a unique tissue, having to coordinate between temporal changes in myofiber metabolism and hypertrophy/atrophy stimuli within a tissue with considerable protein content. Skeletal muscle manages the push and pull between anabolic and catabolic pathways through key regulatory proteins to promote energy production in times of nutrient deprivation or activate anabolic pathways in times of nutrient availability and anabolic stimuli. Branched-chain amino acids (BCAAs) can be used for both energy production and signaling to induce protein synthesis. The metabolism of BCAAs occur in tandem with energetic and anabolic processes, converging at several points along their respective pathways. The fate of intramuscular BCAAs adds another layer of regulation, which has consequences to promote or inhibit muscle fiber protein anabolism. This review will outline the general mechanisms of muscle protein synthesis and describe how metabolic pathways can regulate this process. Lastly, we will discuss how BCAA availability and demand coordinate with synthesis mechanisms and identify key factors involved in intramuscular BCAA trafficking.

Optimizing Adult Protein Intake During Catabolic Health Conditions

ABSTRACT The DRIs define a range of acceptable dietary intakes for each nutrient. The range is defined from the minimum intake to avoid risk of inadequacy (i.e., the RDA) up to an upper limit (UL) based on a detectable risk of adverse effects. For most nutrients, the minimum RDA is based on alleviating a clear deficiency condition, whereas higher intakes are often recommended to optimize specific health outcomes. Evidence is accumulating that similar logic should be applied to dietary recommendations for protein. Although the RDA for protein of 0.8 g/kg body weight is adequate to avoid obvious inadequacies, multiple studies provide evidence that many adults may benefit from protein quantity, quality, and distribution beyond guidelines currently defined by the RDA. Further, the dietary requirement for protein is a surrogate for the constituent amino acids and, in particular, the 9 considered to be indispensable. Leucine provides an important example of an essential amino acid where the RDA of 42 mg/kg body weight is significantly less than the 100–110 mg/kg required to optimize metabolic regulation and skeletal muscle protein synthesis. This review will highlight the benefits of higher protein diets to optimize health during aging, inactivity, bed rest, or metabolic dysfunction such as type 2 diabetes.

Anabolic Properties of Mixed Wheat-Legume Pasta Products in Old Rats: Impact on Whole-Body Protein Retention and Skeletal Muscle Protein Synthesis

The mechanisms that are responsible for sarcopenia are numerous, but the altered muscle protein anabolic response to food intake that appears with advancing age plays an important role. Dietary protein quality needs to be optimized to counter this phenomenon. Blending different plant proteins is expected to compensate for the lower anabolic capacity of plant-based when compared to animal-based protein sources. The objective of this work was to evaluate the nutritional value of pasta products that were made from a mix of wheat semolina and faba bean, lentil, or split pea flour, and to assess their effect on protein metabolism as compared to dietary milk proteins in old rats. Forty-three old rats have consumed for six weeks isoproteic and isocaloric diets containing wheat pasta enriched with 62% to 79% legume protein (depending on the type) or milk proteins, i.e., casein or soluble milk proteins (SMP). The protein digestibility of casein and SMP was 5% to 14% higher than legume-enriched pasta. The net protein utilization and skeletal muscle protein synthesis rate were equivalent either in rats fed legume-enriched pasta diets or those fed casein diet, but lower than in rats fed SMP diet. After legume-enriched pasta intake, muscle mass, and protein accretion were in the same range as in the casein and SMP groups. Mixed wheat-legume pasta could be a nutritional strategy for enhancing the protein content and improving the protein quality, i.e., amino acid profile, of this staple food that is more adequate for maintaining muscle mass, especially for older individuals.