Metabolism of fats and key amino acids differ in DMD boys, study finds

Differences may underlie disease hallmarks like fibrosis, fat replacement

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

A squirting dropper is pictured alongside four vials, each half-filled with a fluid.

The blood of boys with Duchenne muscular dystrophy (DMD) show alterations in the metabolism of fatty molecules, amino acids, and carnitine, a nutrient helping cells produce energy, relative to children without this disease, a study from China reports.

Differences in the gut microbiome, the collection of microorganisms living in the intestinal tract, also were identified, which may be due to the “nutritional disorders and intestinal muscle dysfunction in DMD patients,” the researchers wrote.

Alterations seen are consistent with the clinical features of DMD, such as “recurrent muscle necrosis [death] and regeneration, interstitial fibrosis [scarring], and fat replacement,” they added.

The study, “The metabolomic plasma profile of patients with Duchenne muscular dystrophy: providing new evidence for its pathogenesis,” was published in the Orphanet Journal of Rare Diseases.

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Changes seen in blood samples reflected in clinical features of DMD

DMD is caused by the loss of dystrophin, a key protein for muscle health, due to mutations in the DMD gene. Dystrophin deficiency leads to progressive muscle degeneration and weakness.

Past studies have reported deficits in metabolites, the intermediate or end products of metabolic reactions, in the muscle cells of DMD patients. Most of the reported metabolites are linked with energy and lipid (fat) metabolism.

However, the identity of blood metabolites and metabolic pathways implicated in Duchenne’s disease processes remain relatively understudied, the scientists noted.

Researchers at Sichuan University analyzed plasma samples from 42 DMD boys (mean age of 9.6) and compared them to samples from 40 healthy and age-matched boys, who served as controls.

Mean body weight was lower in DMD boys than in controls (27.4 vs. 32.5 kg, or about 60.4 vs. 71.6 lbs). Almost half of the DMD group were using corticosteroids (22 of 42), and a majority (30) took vitamin D and calcium supplements. At the time of the analysis, four DMD boys had lost the ability to walk independently.

Levels of metabolites in blood samples were analyzed by a technique called liquid chromatography-mass spectrometry, and showed metabolic defects in DMD patients compared with controls.

Different levels in a total of 25 metabolites were evident between both groups. These included amino acids — the building blocks of proteins — lipids, unsaturated fatty acids, carnitine, as well as metabolites related to the gut microbiome.

Pathways significantly altered in DMD patients included the metabolism of linoleic acid (a fatty acid), along with the metabolism of glycerophospholipid (a type of fat), and that of the amino acids alanine, aspartate, and glutamate.

“Fibrosis is one of the pathological features of DMD, and previous studies have found that glutaminolysis [the process by which glutamine changes to glutamate] plays an important role in fibrosis. Enhanced conversion of glutamine to glutamate confers resistance to apoptosis [cell death] and promotes stabilization of collagen,” the researchers wrote, adding their study found “a decrease in plasma glutamate content” in children with Duchenne.

Likewise, “the fatty acid metabolism pathway is dysregulated in DMD … [and] may be one of the reasons for enhanced muscle fat replacement in patients,” they added.

Blood metabolites help in understanding mechanisms at play in disease

Studying the blood metabolites of DMD patients “enables us to better understand the underlying mechanisms of DMD from the perspective of circulation metabolism and thus provides potential therapeutic targets,” the team wrote.

Researchers noted that that their study was limited by its small number of patients, and that treatment type, courses, and doses of corticosteroids varied, precluding a comparison of patients with and without treatment.

“Although we cannot separate DMD patients into treated and untreated group, this article can still be considered as the first exploratory study on metabolic changes in clinical patients with DMD (regardless of medication use) in natural research history,” the scientists concluded. “In the future, we will conduct a prospective study with larger samples to focus on drug treatments (such as glucocorticoids, calcium channel blockers and vitamin D) and explore their impacts on the metabolic spectrum of DMD patients.”