Soraia Poloni

Stearoyl-CoA Desaturase-1: Is It the Link between Sulfur Amino Acids and Lipid Metabolism?

An association between sulfur amino acids (methionine, cysteine, homocysteine and taurine) and lipid metabolism has been described in several experimental and population-based studies. Changes in the metabolism of these amino acids influence serum lipoprotein concentrations, although the underlying mechanisms are still poorly understood. However, recent evidence has suggested that the enzyme stearoyl-CoA desaturase-1 (SCD-1) may be the link between these two metabolic pathways. SCD-1 is a key enzyme for the synthesis of monounsaturated fatty acids. Its main substrates C16:0 and C18:0 and products palmitoleic acid (C16:1) and oleic acid (C18:1) are the most abundant fatty acids in triglycerides, cholesterol esters and membrane phospholipids. A significant suppression of SCD-1 has been observed in several animal models with disrupted sulfur amino acid metabolism, and the activity of SCD-1 is also associated with the levels of these amino acids in humans. This enzyme also appears to be involved in the etiology of metabolic syndromes because its suppression results in decreased fat deposits (regardless of food intake), improved insulin sensitivity and higher basal energy expenditure. Interestingly, this anti-obesogenic phenotype has also been described in humans and animals with sulfur amino acid disorders, which is consistent with the hypothesis that SCD-1 activity is influenced by these amino acids, in particularly cysteine, which is a strong and independent predictor of SCD-1 activity and fat storage. In this narrative review, we discuss the evidence linking sulfur amino acids, SCD-1 and lipid metabolism.

Body composition in patients with classical homocystinuria: body mass relates to homocysteine and choline metabolism

INTRODUCTION Classical homocystinuria is a rare genetic disease caused by cystathionine β-synthase deficiency, resulting in homocysteine accumulation. Growing evidence suggests that reduced fat mass in patients with classical homocystinuria may be associated with alterations in choline and homocysteine pathways. This study aimed to evaluate the body composition of patients with classical homocystinuria, identifying changes in body fat percentage and correlating findings with biochemical markers of homocysteine and choline pathways, lipoprotein levels and bone mineral density (BMD) T-scores. METHODS Nine patients with classical homocystinuria were included in the study. Levels of homocysteine, methionine, cysteine, choline, betaine, dimethylglycine and ethanolamine were determined. Body composition was assessed by bioelectrical impedance analysis (BIA) in patients and in 18 controls. Data on the last BMD measurement and lipoprotein profile were obtained from medical records. RESULTS Of 9 patients, 4 (44%) had a low body fat percentage, but no statistically significant differences were found between patients and controls. Homocysteine and methionine levels were negatively correlated with body mass index (BMI), while cysteine showed a positive correlation with BMI (p<0.05). There was a trend between total choline levels and body fat percentage (r=0.439, p=0.07). HDL cholesterol correlated with choline and ethanolamine levels (r=0.757, p=0.049; r=0.847, p=0.016, respectively), and total cholesterol also correlated with choline levels (r=0.775, p=0.041). There was no association between BMD T-scores and body composition. CONCLUSIONS These results suggest that reduced fat mass is common in patients with classical homocystinuria, and that alterations in homocysteine and choline pathways affect body mass and lipid metabolism.

CBS mutations are good predictors for B6‐responsiveness: A study based on the analysis of 35 Brazilian Classical Homocystinuria patients

Classical homocystinuria (HCU) is a monogenic disease caused by the deficient activity of cystathionine β‐synthase (CβS). The objective of this study was to identify the CBS mutations in Brazilian patients with HCU.

Cytokines levels in late-diagnosed Classical Homocystinuria patients

Classical homocystinuria (HCU; CβS deficiency) is characterized by a blockage in homocysteine (Hcy) degradation, resulting in Hcy and methionine accumulation and cysteine deficiency. Studies in healthy and chronically ill individuals have found positive associations between proinflammatory cytokines and plasma total homocysteine (tHcy) [1–3], suggesting a role for immunomodulation in HCU pathogenesis. Therefore, we aimed to investigate 20 inflammatory cytokines in plasma of poorly controlled HCU patients and healthy controls. The study sample comprised 9 late-diagnosed HCU patients and 10 age and gender-matched healthy controls from South Brazil. tHcy, cysteine, methionine, S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) were measured in plasma by LC-MS/MS. The cytokines quantification assay was performed through EMD Millipores MILLIPEX® MAP Human Cytokine kit, accordingly manufacturers instruction. All samples were measured in duplicates for 20 cytokines (Table 1). Measurements with divergence ≥30% between duplicates

Diagnosis and Management of Classical Homocystinuria in Brazil: A Summary of 72 Late-Diagnosed Patients

This study described a broad clinical characterization of classical homocystinuria (HCU) in Brazil. This was a cross-sectional, observational study including clinical and biochemical data from 72 p...

Leptin concentrations and SCD-1 indices in classical homocystinuria: Evidence for the role of sulfur amino acids in the regulation of lipid metabolism

BACKGROUND We describe body composition, lipid metabolism and Stearoyl-CoA desaturase-1 (SCD-1) indices in patients with classical homocystinuria (HCU). METHODS Eleven treated HCU patients and 16 healthy controls were included. Body composition and bone mineral density were assessed by dual X-ray absorptiometry. Sulfur amino acids (SAA) and their derivatives (total homocysteine, cysteine, methionine, S-adenosylmethionine, S-adenosylhomocysteine, and glutathione), lipids (free fatty acids, acylcarnitines, triglycerides and lipoproteins), glucose, insulin, leptin, adiponectin, and isoprostanes were measured in plasma. Insulin resistance was evaluated by HOMA-IR. To estimate liver SCD-1 activity, SCD-16 [16:1(n-7)/16:0] and SCD-18 [18:1(n-9)/18:0] desaturation indices were determined. RESULTS In HCU patients, SCD-16 index was significantly reduced (p=0.03). A trend of an association of SCD-16 index with cysteine was observed (r=0.624, p=0.054). HCU patients displayed lower lean mass (p<0.05), with no differences in fat mass percentage. Leptin and low-density lipoprotein concentrations were lower in HCU patients (p<0.05). Femur bone mineral density Z-scores were correlated with plasma cysteine (r=0.829; p=0.04) and total homocysteine (r=-0.829; p=0.04) in HCU patients. CONCLUSIONS We report alterations in leptin and SCD-1 in HCU patients. These results agree with previous findings from epidemiologic and animal studies, and support a role for SAA on lipid homeostasis.