Abnormal fatty acid metabolism may play role in scleroderma: Analysis
Researchers ID 3 genes that were significantly dysregulated in SSc patients
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Abnormal fatty acid metabolism may play a role in the development of systemic sclerosis (SSc), according to a gene activity analysis.
Researchers identified three genes involved in fatty acid metabolism that were significantly dysregulated in SSc patients. These changes correlated with markers of fat metabolism and disease complications, including lung involvement, the data suggested.
These findings indicate that “dysregulated fatty acid metabolism may be implicated in the [development] of SSc,” which may provide “potential targets for metabolic intervention,” researchers wrote in the study, “Expression and clinical significance of fatty acid metabolism–related genes in PBMCs of SSc patients,” which was published in Clinical Rheumatology.
Disruptions in fatty acid metabolism in SSc linked to inflammation
SSc, also called scleroderma, is an autoimmune disease characterized by the abnormal accumulation of scar tissue in the skin and connective tissues, affecting blood vessels and internal organs such as the lungs, heart, and kidneys.
Metabolism of fatty acids, essential biochemicals involved in energy storage, cell structure (membranes), and signaling, has been implicated in the onset and progression of several autoimmune diseases, including lupus and rheumatoid arthritis. In fact, disruptions in fatty acid metabolism in SSc have been linked to inflammation, scarring, and blood vessel dysfunction.
To further investigate the role of fatty acid metabolism in SSc, scientists in China conducted a computational analysis to identify SSc-associated fatty acid metabolism genes. They validated the findings using patient blood samples.
“The primary objective of this analysis was to determine whether these genes are associated with specific clinical characteristics or disease subtypes in SSc and to evaluate their potential as biomarkers for disease progression or therapeutic targets,” the team wrote.
Three genes significantly upregulated in SSc
The researchers first analyzed two publicly available datasets with information on overall gene activity in SSc patients versus healthy controls. Some patients had SSc-related conditions, including pulmonary arterial hypertension (PAH), a condition marked by high pressure in the blood vessels of the lungs, and interstitial lung disease (ILD), characterized by fibrosis (scarring) in the lungs.
The computer-based analysis identified five fatty acid metabolism genes in SSc patients: HIBCH, ACADM, IDH1, ACOX1, and SUCLA2.
To verify these findings, the team collected clinical data and blood samples from 69 SSc patients (84.3% women) and 70 healthy individuals matched by age and sex to the patients who served as controls.
Blood tests revealed certain changes in SSc patients compared with controls. This included higher levels of triglycerides (a type of fat), white blood cells (a marker of inflammation), and AST (a marker for liver damage). At the same time, patients also had lower levels of total cholesterol, high-density lipoprotein (“good” cholesterol), and hemoglobin (the protein in red blood cells that carries oxygen).
Fatty acid metabolism plays an important role in regulating immune function and is involved in the pathogenesis [disease processes] of SSc.
When the researchers measured the activity of the five previously identified fatty acid genes in immune cells isolated from blood samples, HIBCH, ACADM, and ACOX1 were significantly upregulated (had higher activity) in SSc patients than in controls, whereas IDH1 and SUCLA2 were not. The three upregulated genes encode enzymes that play roles in metabolic pathways, primarily the breakdown of specific fatty acids and amino acids, the building blocks of proteins.
Across subgroups, ACADM and ACOX1 were significantly upregulated in patients with SSc and ILD without PAH compared with those without ILD or PAH, whereas HIBCH was not. Further analysis found that higher ACADM activity correlated with lower total cholesterol and high-density lipoprotein levels in blood.
In addition, HIBCH and ACOX1 were significantly upregulated in SSc patients with both PAH and ILD compared with those with SSc and ILD alone. Among these patients, higher ACOX1 activity correlated with lower levels of total cholesterol and low-density and very low-density lipoprotein cholesterol, known as “bad” cholesterol.
“Fatty acid metabolism plays an important role in regulating immune function and is involved in the pathogenesis [disease processes] of SSc,” the researchers concluded. “Further large-scale validation and research on the molecular mechanisms of SSc are needed to explore the roles of these genes.”
