Markers of Metabolic Abnormalities in Vitiligo Patients

Abstract

While vitiligo is primarily caused by melanocyte deficiency or dysfunction, recent studies have revealed a notable prevalence of metabolic syndrome (MetS) among patients with vitiligo. This suggests shared pathogenic features between the two conditions. Individuals with vitiligo often exhibit variations in triglyceride levels, cholesterol, and blood pressure, which are also affected in MetS. Given the similarities in their underlying mechanisms, genetic factors, pro-inflammatory signalling pathways, and increased oxidative stress, this study aims to highlight the common traits between vitiligo and metabolic systemic disorders. Serum analyses confirmed increased low-density lipoprotein (LDL) levels in patients with vitiligo, compared to physiological values. In addition, we reported significant decreases in folate and vitamin D (Vit D) levels. Oxidative stress is one of the underlying causes of the development of metabolic syndromes and is related to the advancement of skin diseases. This study found high levels of inflammatory cytokines, such as interleukin-6 (IL-6) and chemokine 10 (CXCL10), which are markers of inflammation and disease progression. The accumulation of insulin growth factor binding proteins 5 (IGFBP5) and advanced glycation end products (AGEs) entailed in atherosclerosis and diabetes onset, respectively, were also disclosed in vitiligo. In addition, the blood-associated activity of the antioxidant enzymes catalase (Cat) and superoxide dismutase (SOD) was impaired. Moreover, the plasma fatty acid (FAs) profile analysis showed an alteration in composition and specific estimated activities of FAs biosynthetic enzymes resembling MetS development, resulting in an imbalance towards pro-inflammatory n6-series FAs. These results revealed a systemic metabolic alteration in vitiligo patients that could be considered a new target for developing a more effective therapeutic approach.

Keywords: comorbidities; inflammation; metabolic syndrome; vitiligo.

Figure 1

Laboratory findings of vitiligo patients. (A) Serum metabolic parameters of vitiligo patients compared to the physiological range. Data are represented as mean ± SD. The dot plot summarized the colorimetric determination of cysteine amount in the vitiligo cohort (VTG) compared to the control group (CTR) (B). A * p-value < 0.05 was considered statistically significant.

Figure 2

Inflammatory state evaluation. Protein detection of several pro-inflammatory markers showed an increase in the level of IL-6 (A), CXCL10 (B) and IGFBP5 (D) in vitiligo patients concerning the controls. In contrast, a decrease in IL-17 (C) was measured. (E) Correlation between serum level of IGFBP5 and cysteine in patients with vitiligo (n = 50). Data are represented as mean ± SD (* p < 0.05, *** p < 0.001).

Figure 3

Serum oxidative biomarkers. Superoxide dismutase activity was significantly lower among patients than controls (A) and correlated with a diminished amount of vitamin D (B). As illustrated, a slight catalase rise was detected in the vitiligo cohort compared to the controls (C). A higher accumulation of AGEs in vitiligo subjects was reported (D). Data are represented as mean ± SD (* p < 0.05; ** p < 0.01).

Figure 4

Circulating Fatty Acids Profile. GCMS analysis of circulating FAs showed similar SFAs, MUFAs, and PUFAs distribution between vitiligo patients and controls (A); vitiligo patients showed alteration in PUFAs composition characterized by an increase in the level of n6-series FAs such as GLA and AA (B) and by a decrease in the level of n3-series FAs in particular EPA (C). An imbalance in FA metabolic pathway was demonstrated by the alteration observed for the estimated desaturase and elongase activities, with the increase in n6/n3 index (D). Data are represented as mean ± SD (* p ≤ 0.05; ** p ≤ 0.01).