Imbalance Between Omega-6- and Omega-3-Derived Bioactive Lipids in Arthritis in Older Adults

Abstract

Elderly-onset rheumatoid arthritis (EORA) and polymyalgia rheumatica (PMR) are common rheumatic diseases in older adults. Oxylipins are bioactive lipids derived from omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFAs) that serve as activators or suppressors of systemic inflammation. We hypothesized that arthritis symptoms in older adults were related to oxylipin-related perturbations. Arthritis in older adults (ARTIEL) is an observational prospective cohort with 64 patients older than 60 years of age with newly diagnosed arthritis. Patients’ blood samples at baseline and 3 months posttreatment were compared with 18 controls. A thorough clinical examination was conducted. Serum oxylipins were determined by mass spectrometry. Data processing and statistical analysis were performed in R. Forty-four patients were diagnosed with EORA and 20 with PMR. At diagnosis, EORA patients had a mean DAS28CRP (Disease Activity Score 28 using C-reactive protein) of 5.77 (SD 1.02). One hundred percent of PMR patients reported shoulder pain and 90% reported pelvic pain. Several n-6- and n-3-derived oxylipin species were significantly different between controls and arthritis patients. The ratio of n-3/n-6 PUFA was significantly downregulated in EORA but not in PMR patients as compared to controls. The top two candidates as biomarkers for differentiating PMR from EORA were 4-HDoHE, a hydroxydocosahexaenoic acid, and 8,15-dihydroxy-eicosatrienoic acid (8,15-diHETE). The levels of n-3-derived anti-inflammatory species increased in EORA after treatment. These results suggest that certain oxylipins may be key effectors in arthrtis in older adults and that the imbalance between n-6- and n-3-derived oxylipins might be related to pathobiology in this population.

The oxylipin profile is associated with development of type 1 diabetes: the Diabetes Autoimmunity Study in the Young (DAISY)

“…The n-3-related oxylipins generally are anti-inflammatory, anti-proliferative and proresolving [10]. Imbalances in n-6 and n-3 oxylipins have been found in patients with the autoimmune conditions ulcerative colitis [11] and arthritis [8,12,13]. In healthy DAISY participants without type 1 diabetes, we found that most oxylipins were significantly associated with their precursor FA (e.g.…”

Increased Epoxyeicosatrienoic Acids and Hydroxyeicosatetraenoic Acids After Treatment of Iodide Intake Adjustment and 1,25-Dihydroxy-Vitamin D3 Supplementation in High Iodide Intake–Induced Hypothyroid Offspring Rats

“…DHETs are the metabolites of EETs hydrolyzed by soluble epoxide hydrolase (sEH) (Yang et al, 2013 ). PGB2 is the metabolite of PGE2 (Coras et al, 2021 ), and PGE2 can promote cell growth and elevate the expression of hypertrophic marker genes by inhibiting the COX2/PGE2 pathway (Zhang et al, 2019 ). PGJ2 is formed by dehydration within the cyclopentenone ring of PGD2 (Abdelrahman et al, 2004 ).…”

“…In addition, the significantly increased TSH level with increased PGB2 and the significantly decreased VD3 level with increased PGB2 and PGJ2 were detected in high iodide intake–induced hypothyroidism. PGB2 is the metabolite of PGE2 (Coras et al, 2021 ), and PGJ2 is formed by dehydration within the cyclopentenone ring of PGD2 (Abdelrahman et al, 2004 ). Tahara et al ( 1991 ) reported that TSH stimulates the production of PGD2 and PGE2 in the Fischer rat thyroid follicular cell line (FRTL-5).…”

“…Arachidonic acid (AA) is synthesized from the n-6 fatty acid. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are synthesized from the n-3 fatty acid (Coras et al, 2021 ). AA and EPA were 20 carbons in the chain, and DHA was 22 carbons in the chain.…”

Mitochondrial Dysfunction and Oxidative Stress in Rheumatoid Arthritis

“…Definitely, it is necessary to keep in mind that prevention is the best treatment. In this sense, a healthy diet based on incorporation of a wide variety of nutrients and preventive nutrition could contribute to reduce the appearance of diseases that arise as a consequence of a deficient or improper diet as several studies suggest could happen with RA [ 33 , 249 , 269 , 303 ]. This way requires the participation of different sectors, both public and private, with national policies that promote a healthy diet.…”