Fatty Acid Synthesis Reduction Associated With Metabolic, Cardiovascular Comorbidities in Gout

Reduction of fatty acid synthesis in response to uric acid lowering therapy may reduce both comorbid metabolic and cardiovascular disease in patients with gout, according to research findings presented at the American College of Rheumatology (ACR) Convergence 2020, held virtually from November 5 to 9, 2020.

Researchers conducted a prospective study to characterize the metabolic profiles of patients with gout and evaluate the association of metabolic and cardiovascular comorbidities with gout and hyperuricemia.

A total of 20 patients who fulfilled the 2015 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) gout classification criteria and had hyperuricemia (45% [n=9] with a flare rate ≥5/yr) were included in the analysis. Blood samples were collected at baseline and at weeks 12 and 24; patients underwent uric acid level titration to achieve serum uric acid target less than 6 mg/dL. Data were extracted, peak-identified, and processed, and both hierarchal clustering and random forest analyses were performed. In terms of treatment, 6 patients were receiving uric acid lowering therapy, but were hyperuricemic; 14 patients were initiated with xanthine oxidase inhibitor therapy with either allopurinol or febuxostat.

Serum uric acid levels were significantly lower at weeks 12 and 24 compared to baseline. Overall, 80% and 90% of patients achieved reduced serum uric acid less than 7 mg/dL at weeks 12 and 24, respectively. Both principal component analysis and hierarchal clustering analysis demonstrated overlap between samples collected at baseline, week 12, and week 24, following treatment. Random forest analysis resulted in predictive accuracy of 52%; several metabolites contributing primarily to separation between baseline and week 24 were also identified. These metabolic sites “pointed heavily towards changes in selected metabolic pathways,” including nucleotide and lipid metabolism.

Two-way repeated analysis of variance (ANOVA) measures identified 115 metabolites — 89 downregulated and 26 upregulated — that differed significantly between baseline and 24 weeks. Short, medium, and long chain fatty acids, as well as biliary acids, were significantly decreased at 24 weeks. Researchers noted that this may suggest an association between urate levels and fatty acid synthesis in both the liver and adipose tissue.

“The metabolomic blood profiles linked with patient response to xanthine oxidase inhibitor [uric acid lowering therapies] indicated a reduction of fatty acid synthesis,” the researchers concluded. “Although further studies are required to investigate how urate modulates lipid metabolism in liver and adipose [tissues], our findings point fatty acid synthesis reduction in response to [uric acid lowering therapies] therapy in gout as being highly pertinent to comorbid metabolic and cardiovascular disease in gout.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Guma M, Coras R, Liu-Bryan R, Terkeltaub R. Sustained treat to target uric acid lowering therapy markedly lowers fatty acid levels in gout patients. Presented at: ACR Convergence 2020; November 5-9, 2020. Abstract 680.