Advertisement

Not all the eggs and the chickens are the same: The case of uric acid and metabolic syndrome

      Uric acid represents the end-product of purine metabolism in humans and the great apes where it has played some evolutive roles over the time [
      • Bardin T.
      • Richette P.
      Definition of hyperuricemia and gouty conditions.
      ]. The production of uric acid is largely regulated by xanthine oxidoreductase (XOR) that is converting hypoxanthine to uric acid and is partially responsible for the increase in the serum levels of urate and its possible biological and pathological effects [
      • Bardin T.
      • Richette P.
      Definition of hyperuricemia and gouty conditions.
      ]. Historically the increase in serum urate has been linked to some dietary habits (e.g. alcohol, red meat, seafood, etc.) that however explain only a minor proportion of the variance in serum uric acid levels when compared with inherited genetic variants [
      • Choi H._.K.
      • Atkinson K.
      • Karlson E.W.
      • Willett W.
      • Curhan G.
      Purine-rich foods, dairy and protein intake, and the risk of gout in men.
      ]. More importantly, uric acid is also synthesized in the liver, intestines, muscle, and vascular endothelium and this endogenous production could be more strictly related to the effects of increased serum urate beyond its crystal precipitation at the level of joints, soft tissue, kidneys, and other organs [
      • El Ridi R.
      • Tallima H.
      Physiological functions and pathogenic potential of uric acid: a review.
      ]. Accumulating evidence has demonstrated the role of increased serum urate as a possible etiologic mechanism in the pathogenesis of cardiovascular, metabolic, and renal diseases [
      • Borghi C.
      • Agabiti-Rosei E.
      • Johnson R.J.
      • Kielstein J.T.
      • Lurbe E.
      • Mancia G.
      • Redon J.
      • Stack A.G.
      • Tsioufis K.P.
      Hyperuricaemia and gout in cardiovascular, metabolic and kidney disease.
      ,
      • Borghi C.
      • Agabiti-Rosei E.
      • Johnson R.J.
      • Kielstein J.T.
      • Lurbe E.
      • Mancia G.
      • Redon J.
      • Stack A.G.
      • Tsioufis K.P.
      Hyperuricaemia and gout in cardiovascular, metabolic and kidney disease.
      ,
      • Borghi C.
      • Agnoletti D.
      • Cicero A.F.G.
      • Lurbe E.
      • Virdis A.
      Uric acid and hypertension: a review of evidence and future perspectives for the management of cardiovascular risk.
      ]. In particular, the presence of hyperuricemia above the levels of 5.5 mg/dL has been reported as a risk factors for hypertension, atrial fibrillation (AF), chronic kidney disease (CKD), heart failure (HF), coronary artery disease (CAD), and cardiovascular death [
      • Borghi C.
      • Agabiti-Rosei E.
      • Johnson R.J.
      • Kielstein J.T.
      • Lurbe E.
      • Mancia G.
      • Redon J.
      • Stack A.G.
      • Tsioufis K.P.
      Hyperuricaemia and gout in cardiovascular, metabolic and kidney disease.
      ,
      • Borghi C.
      • Agabiti-Rosei E.
      • Johnson R.J.
      • Kielstein J.T.
      • Lurbe E.
      • Mancia G.
      • Redon J.
      • Stack A.G.
      • Tsioufis K.P.
      Hyperuricaemia and gout in cardiovascular, metabolic and kidney disease.
      ]. In addition, elevated levels of serum uric acid have been reported to increase the relative risk of diabetes and metabolic syndrome acting though an interference with insulin sensitivity that has been reported as significantly reduced in presence of increased serum urate before the development of hyperglycemia and correlated risk factors [
      • Han T.
      • Lan L.
      • Qu R.
      • Xu Q.
      • Jiang R.
      • Na L.
      • Sun C
      Temporal relationship between hyperuricemia and insulin resistance and its impact on future risk of hypertension.
      ]. This observations and many others in the same direction have supported the idea that uric acid per se or the mechanism of its production can be involved in the progressive reduction in tissue insulin sensitivity that may explain the progression toward metabolic abnormalities, increased blood pressure and atherogenic dyslipidemia that can largely contribute to the excess in the risk of cardiovascular disease observed in patients with elevated serum urate levels.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to European Journal of Internal Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Bardin T.
        • Richette P.
        Definition of hyperuricemia and gouty conditions.
        Curr Opin Rheumatol. 2014; 26: 186-191
        • Choi H._.K.
        • Atkinson K.
        • Karlson E.W.
        • Willett W.
        • Curhan G.
        Purine-rich foods, dairy and protein intake, and the risk of gout in men.
        N Engl J Med. 2004; 350: 1093-1103
        • El Ridi R.
        • Tallima H.
        Physiological functions and pathogenic potential of uric acid: a review.
        J Adv Res. 2017; 8: 487-493
        • Borghi C.
        • Agabiti-Rosei E.
        • Johnson R.J.
        • Kielstein J.T.
        • Lurbe E.
        • Mancia G.
        • Redon J.
        • Stack A.G.
        • Tsioufis K.P.
        Hyperuricaemia and gout in cardiovascular, metabolic and kidney disease.
        Eur J Intern Med. 2020; 80: 1-11
        • Borghi C.
        • Agabiti-Rosei E.
        • Johnson R.J.
        • Kielstein J.T.
        • Lurbe E.
        • Mancia G.
        • Redon J.
        • Stack A.G.
        • Tsioufis K.P.
        Hyperuricaemia and gout in cardiovascular, metabolic and kidney disease.
        Eur J Intern Med. 2020; 80: 1-11
        • Borghi C.
        • Agnoletti D.
        • Cicero A.F.G.
        • Lurbe E.
        • Virdis A.
        Uric acid and hypertension: a review of evidence and future perspectives for the management of cardiovascular risk.
        Hypertension. 2022 Jun 6; (101161HYPERTENSIONAHA12217956)
        • Han T.
        • Lan L.
        • Qu R.
        • Xu Q.
        • Jiang R.
        • Na L.
        • Sun C
        Temporal relationship between hyperuricemia and insulin resistance and its impact on future risk of hypertension.
        Hypertension. 2017; 70 (Oct): 703-711
        • Copur S.
        • Demiray A.
        • Kanbay M.
        Uric acid in metabolic syndrome: does uric acid have e definitive role?.
        Eur J Int Med. 2022; 103: 4-12
        • Sun H.L.
        • Pei D.
        • Lue K.H.
        • Chen Y.L
        Uric acid levels can predict metabolic syndrome and hypertension in adolescents: a 10-year longitudinal study.
        PLoS ONE. 2015; 10e0143786
        • King C.
        • Lanaspa M.A.
        • Jensen T.
        • Tolan D.R.
        • Sanchez-Lozada L.G.
        • Johnson R.J.
        Uric acid as a cause of the metabolic syndrome.
        Contrib Nephrol. 2018; 192: 88-102
        • Lima W.G.
        • Martins-Santos M.E.
        • Chaves V.E.
        Uric acid as a modulator of glucose and lipid metabolism.
        Biochimie. 2015; 116: 17-23
        • Zhu Y.
        • Hu Y.
        • Huang T.
        • Zhang Y.
        • Li Z.
        • Luo Luo Y
        • Yuan H.
        • Hisatome I.
        • Yamamoto T.
        • Cheng J
        High uric acid directly inhibits insulin signalling and induces insulin resistance.
        Biochem Biophys Res Commun. 2014; 447: 707-714
        • Polito L.
        • Bortolotti M.
        • Battelli M.G.
        • Bologne-si A.
        Xanthine oxidoreductase: a leading actor in cardiovascular disease drama.
        Redox Biol. 2021; 48102195
        • Ndrepepa G.
        Uric acid and cardiovascular disease.
        Clin Chim Acta. 2018; 484: 150-163
        • Wang A Tian X.
        • Wu S.
        • Zuo Y.
        • Chen S.
        • Mo D.
        • Luo Y.
        • Wang Y.
        Metabolic factors mediate the association between serum uric acid to serum creatinine ratio and cardiovascular disease.
        Am Heart Assoc. 2021; 10e023054https://doi.org/10.1161/JAHA.121.023054
        • Seo Y.B.
        • Han A.L.
        Association of the serum uric acid-to-creatinine ratio with nonalcoholic fatty liver disease diagnosed by computed tomography.
        Metab Syndr Relat Disord. 2021; 19: 70-75