Mitochondrial dysfunction: The pathological link between psoriasis and insulin resistance?

Abstract

Background Psoriasis is strongly associated with insulin resistance (IR). Lipid profile disturbances and upregulation of enzymes crucial for fatty acid oxidation have been reported in patients with psoriasis. Mitochondrial ß‐oxidation is altered in patients with IR. Common mitochondrial dysfunction may be involved in the origin of both diseases. Objective This study aimed to evaluate mitochondrial ß‐oxidation, intermediary metabolism, and mitochondrial content in psoriatic patients with or without IR and compare them to healthy controls. Methods The participants were divided into three groups: (1) psoriasis and IR (n = 26); (2) psoriasis without IR (n = 17); and (3) healthy controls (n = 17). Quantification of amino acids and acylcarnitines (AC) by tandem mass spectrometry, determination of urinary organic acids by gas chromatography/mass spectrometry (GC/MS), and mitochondrial DNA quantification were performed in all groups. Results When comparisons were made between the two psoriatic groups, no differences were found between: C5DC + C6OH, C16:1, Met/Leu, Met/Phe, C16:1/C16, and C5DC + C6OH/C4DC + C5OH ratios. Nine analytes were different: phenylalanine, Cit/Phe, and Cit/Tyr ratios, C0, C3, C5, C6DC, C16, and C18:1OH. There were no correlations between psoriasis area and severity index (PASI), body mass index (BMI) and duration of disease with ACs. A higher proportion of patients with psoriasis showed increased urine levels of uric acid and hippuric acid (p = 0.01). The mtDNA content was significantly higher in cases than in controls, with no differences between IR and non‐IR psoriatic patients. Conclusions Psoriasis patients with and without IR have a different acylcarnitine profile reflecting impaired ß‐oxidation. A distinctive profile of acylcarnitines suggests an involvement of mitochondrial function associated with an increase in stearoyl CoA desaturase (SCD) activity in psoriatic patients with and without IR.

A Solid-Phase Microextraction—Liquid Chromatography-Mass Spectrometry Method for Analyzing Serum Lipids in Psoriatic Disease

“…Previous studies have found changes in the levels of acylcarnitines in patients with diabetes [ 44 , 45 ], obesity [ 45 ], and heart disease [ 46 ], which are all comorbidities of psoriatic disease. Interestingly, a recent study by Villarreal-Martinez revealed that PsC patients with insulin resistance had a distinct acylcarnitine profile from patients without insulin resistance, reflecting impaired beta-oxidation [ 47 ]. It appears acylcarnitines may be a possible connection between dysregulated fatty acid metabolism seen in previous metabolomic studies and the high prevalence of metabolic abnormalities in patients with psoriatic disease.…”