Medium‐ and long‐chain acylcarnitines are associated with osteoarthritis severity and arterial stiffness in end‐stage osteoarthritis patients: a case‐control study

Tootsi, Kaspar; Kals, Jaak; Zilmer, Mihkel; Paapstel, Kaido; Ottas, Aigar; Märtson, Aare

doi:10.1111/1756-185x.13251

Cited by 24 publications

(23 citation statements)

References 35 publications

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“…C2, the acetylated form of carnitine, plays an integral role in the transport of fatty acids to the mitochondria, where they are oxidized to generate acetyl coenzyme A (CoA) for energy production . Recently, Tootsi et al studied 70 end‐stage OA patients prior to joint replacement and 82 age‐matched controls and found that levels of medium‐ and long‐chain acylcarnitines were significantly decreased in OA patients and were associated with OA radiographic severity. We previously studied the metabolic profiles of synovial fluid samples of 80 end‐stage OA patients who underwent TJR and found that there were two distinct groups, with one group having significantly lower concentrations of all the acylcarnitines measured in the study, as well as a high prevalence of metabolic‐related and cardiovascular diseases .…”

Section: Discussionmentioning

confidence: 99%

Metabolomics Signature for Non‐Responders to Total Joint Replacement Surgery in Primary Osteoarthritis Patients: The Newfoundland Osteoarthritis Study

Costello

Liu

et al. 2019

Journal Orthopaedic Research

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Although total joint replacement (TJR) surgery is considered as the most effective treatment for advanced osteoarthritis (OA) patients, up to one‐third of patients reported unfavorable long‐term post‐operative pain outcomes. We aimed to identify metabolic biomarkers to predict non‐responders to TJR using a metabolomics approach. TJR patients were recruited and followed‐up at least 1‐year post‐surgery; TJR outcomes were assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function subscales. Targeted metabolomic profiling was performed on plasma samples collected pre‐surgery and pairwise metabolite ratios, as proxies for enzymatic reactions, were calculated. Association tests were performed between each metabolite ratio and non‐responders. The metabolome‐wide significance was defined as p < 2 × 10−5. A total of 461 TJR patients due to primary OA were included in the analysis. Fifteen percent of patients were classified as pain non‐responders; 16% were classified as function non‐responders. Lower baseline WOMAC pain and function scores were significantly associated with pain and function non‐responders, respectively (both p < 0.03). Two metabolite ratios were significantly associated with pain non‐responders; acetylcarnitine (C2) to phosphatidylcholine acyl‐alkyl C40:1 (PC ae C40:1) was five times higher in pain non‐responders whereas phosphatidylcholine diacyl C36:4 (PC aa C36:4) to isoleucine was twenty one times lower in pain non‐responders than responders (all p ≤ 1.93 × 10−5). One metabolite ratio, glutamine to isoleucine, was significantly lower in function non‐responders than responders (eight times lower; p = 1.08 × 10−5). Three metabolite ratios (C2 to PC ae C40:1, PC aa C36:4, and glutamine to isoleucine) related to inflammation and muscle breakdown could be considered as novel plasma markers for predicting non‐responders to TJR and warrant further investigation. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:793‐802, 2020

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Section: Discussionmentioning

confidence: 99%

Metabolomics Signature for Non‐Responders to Total Joint Replacement Surgery in Primary Osteoarthritis Patients: The Newfoundland Osteoarthritis Study

Costello

Liu

et al. 2019

Journal Orthopaedic Research

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“…It is regulated by controlling mitochondrial uptake of fatty acids by the carnitine shuttle. Tootsi et al [34] studied 70 end-stage OA patients before joint replacement and 82 age-matched controls and found that serum levels of medium- and long-chain acylcarnitines were significantly decreased in OA patients and were associated with OA radiographic severity. Further, this study showed that the acylcarnitines were associated arterial stiffness, suggesting acylcarnitines might play an important role in the link between OA and cardiovascular diseases.…”

Section: Energy Metabolic Pathwaysmentioning

confidence: 99%

Alteration of Metabolic Pathways in Osteoarthritis

Zhai

2019

Metabolites

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Sir Archibald Edward Garrod, who pioneered the field of inborn errors of metabolism and first elucidated the biochemical basis of alkaptonuria over 100 years ago, suggested that inborn errors of metabolism were “merely extreme examples of variations of chemical behavior which are probably everywhere present in minor degrees, just as no two individuals of a species are absolutely identical in bodily structure neither are their chemical processes carried out on exactly the same lines”, and that this “chemical individuality [confers] predisposition to and immunities from various mishaps which are spoken of as diseases”. Indeed, with advances in analytical biochemistry, especially the development of metabolomics in the post-genomic era, emerging data have been demonstrating that the levels of many metabolites do show substantial interindividual variation, and some of which are likely to be associated with common diseases, such as osteoarthritis (OA). Much work has been reported in the literature on the metabolomics of OA in recent years. In this narrative review, we provided an overview of the identified alteration of metabolic pathways in OA and discussed the role of those identified metabolites and related pathways in OA diagnosis, prognosis, and treatment.

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“…The most common reported changes is an increase in blood concentration of LC acylcarnitines in individuals with age-related diseases [ 11 – 14 ]. Dysregulation of acylcarnitine homeostasis has been tied to a variety of age-related diseases, including cardiovascular disease [ 11 , 12 , 15 ], type II diabetes mellitus [ 13 , 16 , 17 ], osteoarthritis [ 18 ], chronic obstructive pulmonary disease [ 19 ], macular degeneration [ 14 ], glaucoma [ 20 ] and Alzheimer’s disease [ 21 – 23 ]. In addition to the association with age-related diseases, abnormal acylcarnitine levels are associated with activation of inflammation [ 24 ] and mitochondrial dysfunction [ 25 , 26 ].…”

Section: Introductionmentioning

confidence: 99%

Plasma acylcarnitine levels increase with healthy aging

Jarrell

Smith

et al. 2020

Aging

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Acylcarnitines transport fatty acids into mitochondria and are essential for β-oxidation and energy metabolism. Decreased mitochondrial activity results in increased plasma acylcarnitines, and increased acylcarnitines activate proinflammatory signaling and associate with age-related disease. Changes in acylcarnitines associated with healthy aging, however, are not well characterized. In the present study, we examined the associations of plasma acylcarnitines with age (range: 20-90) in 163 healthy, non-diseased individuals from the predictive medicine research cohort (NCT00336570) and tested for gender-specific differences. The results show that long-chain and very long-chain acylcarnitines increased with age, while many odd-chain acylcarnitines decreased with age. Gender-specific differences were observed for several acylcarnitines, e.g., eicosadienoylcarnitine varied with age in males, and hydroxystearoylcarnitine varied in females. Metabolome-wide association study (MWAS) of age-associated acylcarnitines with all untargeted metabolic features showed little overlap between genders. These results show that plasma concentrations of acylcarnitines vary with age and gender in individuals selected for criteria of health. Whether these variations reflect mitochondrial dysfunction with aging, mitochondrial reprogramming in response to chronic environmental exposures, early pre-disease change, or an adaptive response to healthy aging, is unclear. The results highlight a potential utility for untargeted metabolomics research to elucidate gender-specific mechanisms of aging and age-related disease.

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Medium‐ and long‐chain acylcarnitines are associated with osteoarthritis severity and arterial stiffness in end‐stage osteoarthritis patients: a case‐control study

Cited by 24 publications

References 35 publications

Metabolomics Signature for Non‐Responders to Total Joint Replacement Surgery in Primary Osteoarthritis Patients: The Newfoundland Osteoarthritis Study

Metabolomics Signature for Non‐Responders to Total Joint Replacement Surgery in Primary Osteoarthritis Patients: The Newfoundland Osteoarthritis Study

Alteration of Metabolic Pathways in Osteoarthritis

Plasma acylcarnitine levels increase with healthy aging

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