1H-NMR Based Serum Metabolomics Identifies Different Profile between Sarcopenia and Cancer Cachexia in Ageing Walker 256 Tumour-Bearing Rats

Viana, Laís Rosa; Lopes‐Aguiar, Leisa; Rosolen, Rafaela Rossi; Santos, Rogério Willians dos; Marcondes, Maria Cristina Cintra Gomes

doi:10.3390/metabo10040161

Cited by 6 publications

(5 citation statements)

References 38 publications

(55 reference statements)

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“…In cancer cachexia, the mechanisms related to this severe wasting condition are still not fully understood [ 13 , 14 ]. Several metabolomic studies into cancer cachexia were based on metabolomic analysis of the serum, giving a global view of the metabolic alterations induced by this syndrome in the host [ 15 , 16 , 17 , 18 , 19 ]. Despite their importance, they did not provide detailed data on muscle wasting itself.…”

Section: Discussionmentioning

confidence: 99%

A Time-Course Comparison of Skeletal Muscle Metabolomic Alterations in Walker-256 Tumour-Bearing Rats at Different Stages of Life

et al. 2021

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Cancer cachexia is a severe wasting condition that needs further study to find ways to minimise the effects of damage and poor prognosis. Skeletal muscle is the most impacted tissue in cancer cachexia; thus, elucidation of its metabolic alterations could provide a direct clue for biomarker research and be applied to detect this syndrome earlier. In addition, concerning the significant changes in the host metabolism across life, this study aimed to compare the metabolic muscle changes in cachectic tumour-bearing hosts at different ages. We performed 1H-NMR metabolomics in the gastrocnemius muscle in weanling and young adult Walker-256 tumour-bearing rats at different stages of tumour evolution (initial, intermediate, and advanced). Among the 49 metabolites identified, 24 were significantly affected throughout tumour evolution and 21 were significantly affected regarding animal age. The altered metabolites were mainly related to increased amino acid levels and changed energetic metabolism in the skeletal muscle, suggesting an expressive catabolic process and diverted energy production, especially in advanced tumour stages in both groups. Moreover, these changes were more severe in weanling hosts throughout tumour evolution, suggesting the distinct impact of cancer cachexia regarding the host’s age, highlighting the need to adopting the right animal age when studying cancer cachexia.

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Section: Discussionmentioning

confidence: 99%

A Time-Course Comparison of Skeletal Muscle Metabolomic Alterations in Walker-256 Tumour-Bearing Rats at Different Stages of Life

et al. 2021

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“…If this is the case, greater amino acid expression could point to higher muscle degradation in the plantaris. In a previous study by Viana et al, 27 increased amino acid biosynthesis and metabolism correlated with greater muscle degradation in tumorbearing rats. In contrast to the prophylactic processes observed in the laryngeal muscle, no myonuclear divisions occur in the limb muscles (although satellite cells do infuse to injured myofibers to repair already formed muscle).…”

Section: Discussionmentioning

confidence: 71%

Metabolomic Expression of Laryngeal and Hindlimb Muscles in Adult versus Senescent Rats

Shembel

Siu

Lhakhang

et al. 2021

Ann Otol Rhinol Laryngol

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Objectives: (1) Determine the feasibility of obtaining a global, unbiased metabolomic profile on laryngeal muscle in a rat model; (2) evaluate the impact of biological aging on the laryngeal metabolome; and (3) characterize biochemical expression differences between aged and non-aged laryngeal and hindlimb muscle. Methods: Thyroarytenoid laryngeal muscle and plantaris hindlimb muscle were harvested from 5 young adult (9 months old) and 5 older adult (32 months old) F344BN rats. Tissue was processed and analyzed using LC-MS methods. Detected metabolites were compared to widely used metabolite databases and KEGG pathway enrichment was performed on significant metabolites. Results: The greatest differences in metabolite expression were between laryngeal and limb muscle with 126 different metabolites found between laryngeal and limb within the young group and 149 different metabolites within the old group. Significant hits between muscle groups highlighted amino acid differences between these tissues. There were more robust differences with age in limb muscle compared to laryngeal muscle. Conclusions: Amino acid metabolism is a key difference between muscles of the limbs and larynx. Due to the number of differentially expressed metabolites between the 2 muscle groups, caution should be exercised when applying skeletal limb muscle physiology and biology concepts to the vocal muscles in both aged and non-aged musculoskeletal systems. Mechanisms underlying less robust effects of age on laryngeal muscle compared to limb muscle require elucidation.

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“…Given that intertissue cross-talk controls the availability of metabolic fuels for mitochondrial bioenergetics and influences muscle function and quality of life, research efforts have also characterized systemic contributions to sarcopenia. These include chronic low-grade inflammation via pro-inflammatory cytokines, altered metabolic fluxes via reduced circulating levels of anabolic amino acids and perturbations of glucose, vitamin, and lipid metabolism 20 – 25 .…”

Section: Mainmentioning

confidence: 99%

Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia

Membrez,

Migliavacca,

Christen

et al. 2024

Nat Metab

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Mitochondrial dysfunction and low nicotinamide adenine dinucleotide (NAD+) levels are hallmarks of skeletal muscle ageing and sarcopenia1–3, but it is unclear whether these defects result from local changes or can be mediated by systemic or dietary cues. Here we report a functional link between circulating levels of the natural alkaloid trigonelline, which is structurally related to nicotinic acid4, NAD+ levels and muscle health in multiple species. In humans, serum trigonelline levels are reduced with sarcopenia and correlate positively with muscle strength and mitochondrial oxidative phosphorylation in skeletal muscle. Using naturally occurring and isotopically labelled trigonelline, we demonstrate that trigonelline incorporates into the NAD+ pool and increases NAD+ levels in Caenorhabditis elegans, mice and primary myotubes from healthy individuals and individuals with sarcopenia. Mechanistically, trigonelline does not activate GPR109A but is metabolized via the nicotinate phosphoribosyltransferase/Preiss–Handler pathway5,6 across models. In C. elegans, trigonelline improves mitochondrial respiration and biogenesis, reduces age-related muscle wasting and increases lifespan and mobility through an NAD+-dependent mechanism requiring sirtuin. Dietary trigonelline supplementation in male mice enhances muscle strength and prevents fatigue during ageing. Collectively, we identify nutritional supplementation of trigonelline as an NAD+-boosting strategy with therapeutic potential for age-associated muscle decline.

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1H-NMR Based Serum Metabolomics Identifies Different Profile between Sarcopenia and Cancer Cachexia in Ageing Walker 256 Tumour-Bearing Rats

Cited by 6 publications

References 38 publications

A Time-Course Comparison of Skeletal Muscle Metabolomic Alterations in Walker-256 Tumour-Bearing Rats at Different Stages of Life

A Time-Course Comparison of Skeletal Muscle Metabolomic Alterations in Walker-256 Tumour-Bearing Rats at Different Stages of Life

Metabolomic Expression of Laryngeal and Hindlimb Muscles in Adult versus Senescent Rats

Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia

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