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Acute Effects of Cheddar Cheese Consumption on Circulating Amino Acids and Human Skeletal Muscle.

ABSTRACT: Cheddar cheese is a protein-dense whole food and high in leucine content. However, no information is known about the acute blood amino acid kinetics and protein anabolic effects in skeletal muscle in healthy adults. Therefore, we conducted a crossover study in which men and women (n = 24; ~27 years, ~23 kg/m²) consumed cheese (20 g protein) or an isonitrogenous amount of milk. Blood and skeletal muscle biopsies were taken before and during the post absorptive period following ingestion. We evaluated circulating essential and non-essential amino acids, insulin, and free fatty acids and examined skeletal muscle anabolism by mTORC1 cellular localization, intracellular signaling, and ribosomal profiling. We found that cheese ingestion had a slower yet more sustained branched-chain amino acid circulation appearance over the postprandial period peaking at ~120 min. Cheese also modestly stimulated mTORC1 signaling and increased membrane localization. Using ribosomal profiling we found that, though both milk and cheese stimulated a muscle anabolic program associated with mTORC1 signaling that was more evident with milk, mTORC1 signaling persisted with cheese while also inducing a lower insulinogenic response. We conclude that Cheddar cheese induced a sustained blood amino acid and moderate muscle mTORC1 response yet had a lower glycemic profile compared to milk.

SUBMITTER: de Hart NMMP

PROVIDER: S-EPMC7917914 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Acute Effects of Cheddar Cheese Consumption on Circulating Amino Acids and Human Skeletal Muscle.

de Hart Naomi M M P NMMP Mahmassani Ziad S ZS Reidy Paul T PT Kelley Joshua J JJ McKenzie Alec I AI Petrocelli Jonathan J JJ Bridge Michael J MJ Baird Lisa M LM Bastian Eric D ED Ward Loren S LS Howard Michael T MT Drummond Micah J MJ

Nutrients 20210213 2

Cheddar cheese is a protein-dense whole food and high in leucine content. However, no information is known about the acute blood amino acid kinetics and protein anabolic effects in skeletal muscle in healthy adults. Therefore, we conducted a crossover study in which men and women (<i>n</i> = 24; ~27 years, ~23 kg/m<sup>2</sup>) consumed cheese (20 g protein) or an isonitrogenous amount of milk. Blood and skeletal muscle biopsies were taken before and during the post absorptive period following i ...[more]

PMID: 33668674

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Project description:BackgroundCachexia is the direct cause of at least 20% of cancer-associated deaths. Muscle wasting in skeletal muscle results in weakness, immobility, and death secondary to impaired respiratory muscle function. Muscle proteins are massively degraded in cachexia; nevertheless, the molecular mechanisms related to this process are poorly understood. Previous studies have reported conflicting results regarding the amino acid abundances in cachectic skeletal muscle tissues. There is a clear need to identify the molecular processes of muscle metabolism in the context of cachexia, especially how different types of molecules are involved in the muscle wasting process.MethodsNew in situ -omics techniques were used to produce a more comprehensive picture of amino acid metabolism in cachectic muscles by determining the quantities of amino acids, proteins, and cellular metabolites. Using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging, we determined the in situ concentrations of amino acids and proteins, as well as energy and other cellular metabolites, in skeletal muscle tissues from genetic mouse cancer models (n = 21) and from patients with cancer (n = 6). Combined results from three individual MALDI mass spectrometry imaging methods were obtained and interpreted. Immunohistochemistry staining for mitochondrial proteins and myosin heavy chain expression, digital image analysis, and transmission electron microscopy complemented the MALDI mass spectrometry imaging results.ResultsMetabolic derangements in cachectic mouse muscle tissues were detected, with significantly increased quantities of lysine, arginine, proline, and tyrosine (P = 0.0037, P = 0.0048, P = 0.0430, and P = 0.0357, respectively) and significantly reduced quantities of glutamate and aspartate (P = 0.0008 and P = 0.0124). Human skeletal muscle tissues revealed similar tendencies. A majority of altered amino acids were released by the breakdown of proteins involved in oxidative phosphorylation. Decreased energy charge was observed in cachectic muscle tissues (P = 0.0101), which was related to the breakdown of specific proteins. Additionally, expression of the cationic amino acid transporter CAT1 was significantly decreased in the mitochondria of cachectic mouse muscles (P = 0.0133); this decrease may play an important role in the alterations of cationic amino acid metabolism and decreased quantity of glutamate observed in cachexia.ConclusionsOur results suggest that mitochondrial dysfunction has a substantial influence on amino acid metabolism in cachectic skeletal muscles, which appears to be triggered by diminished CAT1 expression, as well as the degradation of mitochondrial proteins. These findings provide new insights into the pathobiochemistry of muscle wasting.

Project description:BACKGROUND:A previous clinical study reported that the addition of an amylopectin/chromium complex (ACr; Velositol®) to 6?g of whey protein (WP) significantly enhanced muscle protein synthesis (MPS). Branched-chain amino acids (BCAAs) are also well-known to enhance MPS. The aim of this study was to determine if the addition of ACr to BCAAs can enhance MPS and activate expression of the mammalian target of the rapamycin (mTOR) pathway compared to BCAAs and exercise alone in exercise-trained rats. METHODS:Twenty-four male Wistar rats were randomly divided into three groups (n?=?8 per group): (I) Exercise control, (II) Exercise plus BCAAs (0.465?g/kg BW, a 6?g human equivalent dose (HED)), and (III) Exercise plus BCAAs (0.465?g/kg BW) and ACr (0.155?g/kg BW, a 2?g HED). All animals were trained with treadmill exercise for 10?days. On the day of the single-dose experiment, rats were exercised at 26?m/min for 2?h and then fed, via oral gavage, study product. One hour after the consumption of study product, rats were injected with a bolus dose (250?mg/kg BW, 25?g/L) of phenylalanine labeled with deuterium to measure the fractional rate of protein synthesis (FSR). Ten minutes later, muscle tissue samples were taken to determine MPS measured by FSR and the phosphorylation of proteins involved in the mTOR pathway including mTOR, S6K1, and 4E-BP1. RESULTS:ACr combined with BCAAs increased MPS by 71% compared to the exercise control group, while BCAAs alone increased MPS by 57% over control (p?<?0.05). ACr plus BCAAs significantly enhanced phosphorylation of mTOR, S6K1 and 4E-BP1 compared to exercise control rats (p?<?0.05). The addition of ACr to BCAAs enhanced insulin levels, mTOR and S6K1 phosphorylation compared to BCAAs alone (p?<?0.05). Serum insulin concentration was positively correlated with the levels of mTOR, (r?=?0.923), S6K1 (r?=?0.814) and 4E-BP1 (r?=?0.953). CONCLUSIONS:In conclusion, the results of this study provide evidence that the addition of ACr to BCAAs significantly enhances exercise-induced MPS, and the phosphorylation of mTOR signaling proteins, compared to BCAAs and exercise alone.

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Acute Effects of Cheddar Cheese Consumption on Circulating Amino Acids and Human Skeletal Muscle.

Publications

Acute Effects of Cheddar Cheese Consumption on Circulating Amino Acids and Human Skeletal Muscle.

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