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Blood Cell Palmitoleate-Palmitate Ratio Is an Independent Prognostic Factor for Amyotrophic Lateral Sclerosis.

Henriques A, Blasco H, Fleury MC, Corcia P, Echaniz-Laguna A, Robelin L, Rudolf G, Lequeu T, Bergaentzle M, Gachet C, Pradat PF, Marchioni E, Andres CR, Tranchant C, Gonzalez De Aguilar JL, Loeffler JP - PLoS ONE (2015)

Bottom Line: Palmitoleate (16:1) and oleate (18:1) levels, and stearoyl-CoA desaturase indices (16:1/16:0 and 18:1/18:0) significantly increased in blood cells from ALS patients compared to healthy controls.In patients with high 16:1/16:0 ratio, survival at blood collection was extended by 10 months, as compared to patients with low ratio.It therefore deserves further validation in larger cohorts for being used to assess disease outcome and effects of disease-modifying drugs.

View Article: PubMed Central - PubMed

Affiliation: INSERM, U1118, Mécanismes Centraux et Périphériques de la Neurodégénerescence, Strasbourg, France; Université de Strasbourg, UMR_S1118, Fédération de Médecine Translationnelle, Strasbourg, France.

ABSTRACT
Growing evidence supports a link between fatty acid metabolism and amyotrophic lateral sclerosis (ALS). Here we determined the fatty acid composition of blood lipids to identify markers of disease progression and survival. We enrolled 117 patients from two clinical centers and 48 of these were age and gender matched with healthy volunteers. We extracted total lipids from serum and blood cells, and separated fatty acid methyl esters by gas chromatography. We measured circulating biochemical parameters indicative of the metabolic status. Association between fatty acid composition and clinical readouts was studied, including ALS functional rating scale-revised (ALSFRS-R), survival, disease duration, site of onset and body mass index. Palmitoleate (16:1) and oleate (18:1) levels, and stearoyl-CoA desaturase indices (16:1/16:0 and 18:1/18:0) significantly increased in blood cells from ALS patients compared to healthy controls. Palmitoleate levels and 16:1/16:0 ratio in blood cells, but not body mass index or leptin concentrations, negatively correlated with ALSFRS-R decline over a six-month period (p<0.05). Multivariate Cox analysis, with age, body mass index, site of onset and ALSFRS-R as covariables, showed that blood cell 16:1/16:0 ratio was an independent prognostic factor for survival (hazard ratio=0.1 per unit of ratio, 95% confidence interval=0.01-0.57, p=0.009). In patients with high 16:1/16:0 ratio, survival at blood collection was extended by 10 months, as compared to patients with low ratio. The 16:1/16:0 index is an easy-to-handle parameter that predicts survival of ALS patients independently of body mass index. It therefore deserves further validation in larger cohorts for being used to assess disease outcome and effects of disease-modifying drugs.

No MeSH data available.


Related in: MedlinePlus

SCD indices are higher in ALS patients than in control subjects.(A) Palmitoleate to palmitate ratio (16:1/16:0) in serum and blood cells from ALS patients (ALS) and control subjects (CT). (B) Oleate to stearate ratio (18:1/18:0) in serum and blood cells from ALS patients (ALS) and control subjects (CT). *p<0.05, **p<0.01, ***p<0.001 (Mann-Withney test, n = 48).
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pone.0131512.g001: SCD indices are higher in ALS patients than in control subjects.(A) Palmitoleate to palmitate ratio (16:1/16:0) in serum and blood cells from ALS patients (ALS) and control subjects (CT). (B) Oleate to stearate ratio (18:1/18:0) in serum and blood cells from ALS patients (ALS) and control subjects (CT). *p<0.05, **p<0.01, ***p<0.001 (Mann-Withney test, n = 48).

Mentions: Notably, the proportion of monounsaturated fatty acids was strongly increased in ALS patients. In particular, palmitoleate and oleate levels increased significantly in blood cells, and higher oleate levels were also observed in serum (Table 2). Palmitoleate and oleate are synthetized by SCD from palmitate and stearate, so that the respective product to substrate ratios are considered as an index of SCD activity [17, 18]. SCD indices 18:1/18:0 and 16:1/16:0 appeared significantly higher in ALS blood cell pellets than in controls. Oleate to stearate ratio was also increased in patients' sera (Fig 1A and 1B).


Blood Cell Palmitoleate-Palmitate Ratio Is an Independent Prognostic Factor for Amyotrophic Lateral Sclerosis.

Henriques A, Blasco H, Fleury MC, Corcia P, Echaniz-Laguna A, Robelin L, Rudolf G, Lequeu T, Bergaentzle M, Gachet C, Pradat PF, Marchioni E, Andres CR, Tranchant C, Gonzalez De Aguilar JL, Loeffler JP - PLoS ONE (2015)

SCD indices are higher in ALS patients than in control subjects.(A) Palmitoleate to palmitate ratio (16:1/16:0) in serum and blood cells from ALS patients (ALS) and control subjects (CT). (B) Oleate to stearate ratio (18:1/18:0) in serum and blood cells from ALS patients (ALS) and control subjects (CT). *p<0.05, **p<0.01, ***p<0.001 (Mann-Withney test, n = 48).
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4492495&req=5

pone.0131512.g001: SCD indices are higher in ALS patients than in control subjects.(A) Palmitoleate to palmitate ratio (16:1/16:0) in serum and blood cells from ALS patients (ALS) and control subjects (CT). (B) Oleate to stearate ratio (18:1/18:0) in serum and blood cells from ALS patients (ALS) and control subjects (CT). *p<0.05, **p<0.01, ***p<0.001 (Mann-Withney test, n = 48).
Mentions: Notably, the proportion of monounsaturated fatty acids was strongly increased in ALS patients. In particular, palmitoleate and oleate levels increased significantly in blood cells, and higher oleate levels were also observed in serum (Table 2). Palmitoleate and oleate are synthetized by SCD from palmitate and stearate, so that the respective product to substrate ratios are considered as an index of SCD activity [17, 18]. SCD indices 18:1/18:0 and 16:1/16:0 appeared significantly higher in ALS blood cell pellets than in controls. Oleate to stearate ratio was also increased in patients' sera (Fig 1A and 1B).

Bottom Line: Palmitoleate (16:1) and oleate (18:1) levels, and stearoyl-CoA desaturase indices (16:1/16:0 and 18:1/18:0) significantly increased in blood cells from ALS patients compared to healthy controls.In patients with high 16:1/16:0 ratio, survival at blood collection was extended by 10 months, as compared to patients with low ratio.It therefore deserves further validation in larger cohorts for being used to assess disease outcome and effects of disease-modifying drugs.

View Article: PubMed Central - PubMed

Affiliation: INSERM, U1118, Mécanismes Centraux et Périphériques de la Neurodégénerescence, Strasbourg, France; Université de Strasbourg, UMR_S1118, Fédération de Médecine Translationnelle, Strasbourg, France.

ABSTRACT
Growing evidence supports a link between fatty acid metabolism and amyotrophic lateral sclerosis (ALS). Here we determined the fatty acid composition of blood lipids to identify markers of disease progression and survival. We enrolled 117 patients from two clinical centers and 48 of these were age and gender matched with healthy volunteers. We extracted total lipids from serum and blood cells, and separated fatty acid methyl esters by gas chromatography. We measured circulating biochemical parameters indicative of the metabolic status. Association between fatty acid composition and clinical readouts was studied, including ALS functional rating scale-revised (ALSFRS-R), survival, disease duration, site of onset and body mass index. Palmitoleate (16:1) and oleate (18:1) levels, and stearoyl-CoA desaturase indices (16:1/16:0 and 18:1/18:0) significantly increased in blood cells from ALS patients compared to healthy controls. Palmitoleate levels and 16:1/16:0 ratio in blood cells, but not body mass index or leptin concentrations, negatively correlated with ALSFRS-R decline over a six-month period (p<0.05). Multivariate Cox analysis, with age, body mass index, site of onset and ALSFRS-R as covariables, showed that blood cell 16:1/16:0 ratio was an independent prognostic factor for survival (hazard ratio=0.1 per unit of ratio, 95% confidence interval=0.01-0.57, p=0.009). In patients with high 16:1/16:0 ratio, survival at blood collection was extended by 10 months, as compared to patients with low ratio. The 16:1/16:0 index is an easy-to-handle parameter that predicts survival of ALS patients independently of body mass index. It therefore deserves further validation in larger cohorts for being used to assess disease outcome and effects of disease-modifying drugs.

No MeSH data available.


Related in: MedlinePlus