Muscle metabolic remodelling patterns in Duchenne muscular dystrophy revealed by ultra-high-resolution mass spectrometry imaging

Dabaj, Ivana; Ferey, Justine; Marguet, Florent; Gilard, Vianney; Basset, Carole; Bahri, Youssef; Bréhin, Anne-Claire; Vanhulle, Catherine; Marret, Stéphane; Laquerrière, Annie; Schmitz-Afonso, Isabelle; Afonso, Carlos; Bekri, Soumeya; Tebani, Abdellah

doi:10.1038/s41598-021-81090-1

Cited by 25 publications

(23 citation statements)

References 50 publications

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“…Elevated PC 34:1/PC 34:2 ratios were detected in DMD muscle, with higher PC 34:1/PC 34:2 ratios detected in more affected areas both in regions of regenerating fibers as well as intercellular spaces ( Tahallah et al, 2008 ). A more recent MS-imaging study also reported enhanced PC 34:1 as a prominent feature of DMD muscle ( Dabaj et al, 2021 ), however, the relationship and impact of the enhanced PC 34:1 to the membrane fragility and progressive muscle wasting remains an open and pressing question.…”

Section: Discussionmentioning

confidence: 99%

Lipidomic Analyses Reveal Specific Alterations of Phosphatidylcholine in Dystrophic Mdx Muscle

et al. 2022

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In Duchenne muscular dystrophy (DMD), lack of dystrophin increases the permeability of myofiber plasma membranes to ions and larger macromolecules, disrupting calcium signaling and leading to progressive muscle wasting. Although the biological origin and meaning are unclear, alterations of phosphatidylcholine (PC) are reported in affected skeletal muscles of patients with DMD that may include higher levels of fatty acid (FA) 18:1 chains and lower levels of FA 18:2 chains, possibly reflected in relatively high levels of PC 34:1 (with 16:0_18:1 chain sets) and low levels of PC 34:2 (with 16:0_18:2 chain sets). Similar PC alterations have been reported to occur in the mdx mouse model of DMD. However, altered ratios of PC 34:1 to PC 34:2 have been variably reported, and we also observed that PC 34:2 levels were nearly equally elevated as PC 34:1 in the affected mdx muscles. We hypothesized that experimental factors that often varied between studies; including muscle types sampled, mouse ages, and mouse diets; may strongly impact the PC alterations detected in dystrophic muscle of mdx mice, especially the PC 34:1 to PC 34:2 ratios. In order to test our hypothesis, we performed comprehensive lipidomic analyses of PC and phosphatidylethanolamine (PE) in several muscles (extensor digitorum longus, gastrocnemius, and soleus) and determined the mdx-specific alterations. The alterations in PC 34:1 and PC 34:2 were closely monitored from the neonate period to the adult, and also in mice raised on several diets that varied in their fats. PC 34:1 was naturally high in neonate’s muscle and decreased until age ∼3-weeks (disease onset age), and thereafter remained low in WT muscles but was higher in regenerated mdx muscles. Among the muscle types, soleus showed a distinctive phospholipid pattern with early and diminished mdx alterations. Diet was a major factor to impact PC 34:1/PC 34:2 ratios because mdx-specific alterations of PC 34:2 but not PC 34:1 were strictly dependent on diet. Our study identifies high PC 34:1 as a consistent biochemical feature of regenerated mdx-muscle and indicates nutritional approaches are also effective to modify the phospholipid compositions.

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Section: Discussionmentioning

confidence: 99%

Lipidomic Analyses Reveal Specific Alterations of Phosphatidylcholine in Dystrophic Mdx Muscle

et al. 2022

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“…Table 3 ). In muscle from DMD (Duchenne muscular dystrophy) patients, increased PC and SM have been reported [ 119 ]. In EDL muscle from the mdx mice (the murine model of DMD, devoid of dystrophin), an increase PC containing saturated acyl chain (16:0 and 18:0) and a decrease PE and PC containing long and polyunsaturated acyl chain (22:6) and (20:4) were found.…”

Section: Importance Of Pls In Striated Muscle Functionsmentioning

confidence: 99%

Phospholipids: Identification and Implication in Muscle Pathophysiology

Bargui

Solgadi

Prost

et al. 2021

IJMS

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Phospholipids (PLs) are amphiphilic molecules that were essential for life to become cellular. PLs have not only a key role in compartmentation as they are the main components of membrane, but they are also involved in cell signaling, cell metabolism, and even cell pathophysiology. Considered for a long time to simply be structural elements of membranes, phospholipids are increasingly being viewed as sensors of their environment and regulators of many metabolic processes. After presenting their main characteristics, we expose the increasing methods of PL detection and identification that help to understand their key role in life processes. Interest and importance of PL homeostasis is growing as pathogenic variants in genes involved in PL biosynthesis and/or remodeling are linked to human diseases. We here review diseases that involve deregulation of PL homeostasis and present a predominantly muscular phenotype.

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“…A variety of muscular dystrophies are associated with a considerably perturbed skeletal muscle metabolism in both the early and acute phase of these disorder [ 318 ], including changed lipid utilisation and impaired energy metabolism in Duchenne patients [ 60 , 176 , 317 ]. Pathological developments in Duchenne children are not only characterised by highly progressive muscle wasting, but also delayed growth resulting in relatively short stature and increased fat mass.…”

Section: Introductionmentioning

confidence: 99%

“…Besides systematic transcriptomic surveys [ 190 , 306 ] and metabolomic research [ 60 , 178 , 345 ] in the field of dystrophinopathy, a major area of omics-based biomarker discovery employs mass spectrometric and proteomic screening protocols for the large-scale identification of new peptides, protein fragments and protein biomarker candidates [ 42 , 82 ]. A few studies have also used multi-omics approaches for studying dystrophic changes at the various levels of biological organisation from gene to mRNA to protein expression [ 122 , 224 , 352 ].…”

Section: Introductionmentioning

confidence: 99%

Complexity of skeletal muscle degeneration: multi-systems pathophysiology and organ crosstalk in dystrophinopathy

Ohlendieck

Swandulla

2021

Pflugers Arch - Eur J Physiol

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Duchenne muscular dystrophy is a highly progressive muscle wasting disorder due to primary abnormalities in one of the largest genes in the human genome, the DMD gene, which encodes various tissue-specific isoforms of the protein dystrophin. Although dystrophinopathies are classified as primary neuromuscular disorders, the body-wide abnormalities that are associated with this disorder and the occurrence of organ crosstalk suggest that a multi-systems pathophysiological view should be taken for a better overall understanding of the complex aetiology of X-linked muscular dystrophy. This article reviews the molecular and cellular effects of deficiency in dystrophin isoforms in relation to voluntary striated muscles, the cardio-respiratory system, the kidney, the liver, the gastrointestinal tract, the nervous system and the immune system. Based on the establishment of comprehensive biomarker signatures of X-linked muscular dystrophy using large-scale screening of both patient specimens and genetic animal models, this article also discusses the potential usefulness of novel disease markers for more inclusive approaches to differential diagnosis, prognosis and therapy monitoring that also take into account multi-systems aspects of dystrophinopathy. Current therapeutic approaches to combat muscular dystrophy are summarised.

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Muscle metabolic remodelling patterns in Duchenne muscular dystrophy revealed by ultra-high-resolution mass spectrometry imaging

Cited by 25 publications

References 50 publications

Lipidomic Analyses Reveal Specific Alterations of Phosphatidylcholine in Dystrophic Mdx Muscle

Lipidomic Analyses Reveal Specific Alterations of Phosphatidylcholine in Dystrophic Mdx Muscle

Phospholipids: Identification and Implication in Muscle Pathophysiology

Complexity of skeletal muscle degeneration: multi-systems pathophysiology and organ crosstalk in dystrophinopathy

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