Inverse Relationship between Serum Lipoxin A4 Level and the Risk of Metabolic Syndrome in a Middle-Aged Chinese Population

Abstract

Metabolic syndrome (MetS) has been identified to be associated with a state of chronic, low-grade inflammation in adipose tissue. Lipoxins are endogenously generated from arachidonic acid, and exhibit anti-inflammatory actions. Currently, there is no available cohort study identifying the association between serum lipoxins level and MetS. Here we investigate the relationship between serum lipoxin A4 (LXA4) level and the risk of incident MetS in a middle-aged Chinese population. A total 624 participants aged 40–65 years were enrolled at baseline, with 417 (including 333 MetS absence) of them were followed up at 2.5 years. Abdominal visceral fat area (VFA) and abdominal subcutaneous fat area (SFA) were determined using MRI. Serum lipoxin A4 levels were measured by ELISA. At baseline, serum LXA4 levels were significantly correlated with a cluster of traditional MetS risk factors related to obesity (P≤0.05). A higher incidence of new Mets was found in the participants of the lowest tertile of LXA4 levels as compared with that in participants of the highest tertile (P = 0.025). Low serum LXA4 levels [OR 2.607(1.151–5.909), P = 0.022] and high VFA [OR 2.571(1.176–5.620), P = 0.018] were associated with an increased incident Mets, respectively, which remained statistically significant after adjustment for age, gender, current smoking, and alcohol drinking status. Logistic regression analysis suggested a combination of low serum LXA4 levels and high WC/VFA might optimize the prediction of incident Mets in middle-aged Chinese population [OR 4.897/4.967, P = 0.009/0.003]. Decrease in serum LXA4 level and increase in VFA are independent predictors of incident Mets in a population-based cohort, and a combination of them enhances the prognostic value of incident Mets. Taken together, our data suggest that serum LXA4 levels might be useful for early detection and prevention of Mets.

Dual modulation of formyl peptide receptor 2 by aspirin‐triggered lipoxin contributes to its anti‐inflammatory activity

“…This result indicates that LXs exert biased allosteric effects on FPR2/ALX signaling. The biased allosteric effects at low concentrations are consistent with physiological levels of LXs shown to be effective in published studies 31,61,62 . The observed inhibition on WKYMVm‐stimulated IL‐8 release by low concentrations of ATL supports the notion that this action of ATL is functionally relevant.…”

AMP-activated protein kinase activation ameliorates eicosanoid dysregulation in high-fat-induced kidney disease in mice

“…In the Japanese population, urinary 8-iso-PGF2α which is a AA metabolite predicts metabolic risks like obesity, hypertension, and glucose tolerance (25). Meanwhile, low serum lipoxin A4 levels (AA metabolite) are associated with metabolic syndrome risk in Chinese population, similar to the elevated kidney levels of lipoxin A4 and its metabolite in our study (26).…”

Fair‐Weather Friends: Evidence of Lipoxin Dysregulation in Neurodegeneration

“…In clinical results the 12/15LOX enzyme is increased in both ischemic stroke patients and in animal models . LX dysregulation may also affect neuronal health as a consequence of systemic inflammatory conditions that may impact neural tissues, such as diabetes and metabolic syndrome . However, it remains unclear how LX actions may impact damage to these attendant neural tissues.…”