Circulating Fractalkine Levels Predict the Development of the Metabolic Syndrome

Abstract

The fractalkine/CX3CR1 axis plays an important role in regulating glucose and lipid metabolism. However, the role of fractalkine in metabolic disorders remains to be fully elucidated. We selected 887 Chinese (40–65 years old) at baseline, with a subgroup of 459 participants examined again 2 years later. The relationship of serum fractalkine levels with the metabolic syndrome (MetS) and its components was investigated. At baseline, participants with MetS had higher fractalkine concentrations than their counterparts without MetS (P < 0.001). At the 2-year follow-up, participants in the highest quartile of baseline fractalkine exhibited higher values for body mass index, waist circumference, waist-to-hip ratio, body fat percentage, glucose, insulin, total cholesterol, triglycerides (TG), and homeostasis model assessment of insulin resistance (HOMA-IR) and lower value for high density lipoprotein-cholesterol (HDL-c) (all P < 0.05). Among 390 participants without MetS at baseline, 45 developed it at year 2. Even after multiple adjustments for visceral adipose tissue area, HOMA-IR, C-reactive protein (CRP), or TG and HDL-c, baseline fractalkine predicted the development of MetS (OR = 7.18, 95%CI: 2.28–18.59). In conclusion, circulating fractalkine predicts the development of the MetS independently of central obesity, CRP, insulin resistance, and dyslipidemia.

CX3CR1 is a gatekeeper for intestinal barrier integrity in mice: Limiting steatohepatitis by maintaining intestinal homeostasis

“…The chemokine receptor CX3CR1 (also known as GPR‐13) has been linked to metabolic syndrome–related diseases, including diabetes, obesity, and atherosclerosis . Due to cleavage of the extracellular domain, higher circulating levels of fractalkine (FKN) are linked to onset of the metabolic syndrome . Interestingly, it is thought that intestinal barrier dysfunction as well as intestinal dysbiosis are also associated with these metabolic disorders .…”

“…The chemokine receptor CX3CR1 (also known as GPR-13) has been linked to metabolic syndromerelated diseases, including diabetes, 5 obesity, 6 and atherosclerosis. 7,8 Due to cleavage of the extracellular domain, higher circulating levels of fractalkine (FKN) are linked to onset of the metabolic syndrome.…”

“…7,8 Due to cleavage of the extracellular domain, higher circulating levels of fractalkine (FKN) are linked to onset of the metabolic syndrome. 6 Interestingly, it is thought that intestinal barrier dysfunction as well as intestinal dysbiosis are also associated with these metabolic disorders. [9][10][11] Intestinal macrophages are defined by their expression of CX3CR1, and MHCII hi CD11b 1 CD11c 1 F4/80 1 CX3CR1 hi macrophages in the gut are critical for intestinal barrier integrity.…”

Modulation of platelet and monocyte function by the chemokine fractalkine (CX3CL1) in cardiovascular disease

“…Also in cardiovascular diseases, membranebound CX 3 CL1 was shown to be upregulated especially by endothelial cells and vascular smooth muscle cells upon stimulation with inflammatory agents [42,46,47]. Increased plasma levels of fractalkine were described for several classical risk factors of cardiovascular diseases, that is in diabetes/metabolic syndrome, obesity [48,49], smoking [50], hypertension [51] and hyperlipidaemia [40]. When plasma chemokine levels were measured in patients with atrial fibrillation, an independent association between low plasma fractalkine levels and low risk of major cardiovascular events was observed.…”

Anti-inflammatory properties of bone morphogenetic protein 4 in human adipocytes

“…The pro-inflammatory cytokines secreted by WAT from obese individuals include tumor necrosis factor alpha (TNF-α), monocyte chemoattractant protein 1 (MCP-1), IL-6, leptin, visfatin, resistin, angiotensin II, and plasminogen activator inhibitor 1 (PAI-1) 6 . Additionally, pro-inflammatory cytokines RANTES and fractalkine were recently suggested as factors increased in obese patients with metabolic syndrome or type-2 diabetes, respectively [7][8][9][10] . In contrast, WAT from lean individuals produces predominantly anti-inflammatory cytokines such as adiponectin, transforming growth factor beta (TGFβ), interleukin (IL)-10, IL-4, IL-13, IL-1 receptor antagonist (IL-1Ra), and apelin 6 .…”