Limits...
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

Blood cell 16:1/16:0 ratio is associated with leptin levels and BMI.Circulating amounts of leptin (A, C) and BMI (B, D) in patients with low or high 16:1/16:0 ratio, and in patients with low or high 18:1/18:0 ratio (Mann-Withney test, n = 117). (E, F) Correlation between leptin levels (A) or BMI (C) and ALSFRS-R slope, determined as the decline of the score over a period of six months starting at the point of blood collection. Correlation coefficients (r) are indicated. n.s., non-significant p-value (Spearman test, n = 111). (G, H) Kaplan-Meier curves of survival in patients with low or high leptin levels, and in patients with low or high BMI, according to the median values of the population. Survival was the interval between the point of blood collection and death. n.s., non-significant p-value (Gehan-Breslow-Wilcoxon test, n = 117).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4492495&req=5

pone.0131512.g003: Blood cell 16:1/16:0 ratio is associated with leptin levels and BMI.Circulating amounts of leptin (A, C) and BMI (B, D) in patients with low or high 16:1/16:0 ratio, and in patients with low or high 18:1/18:0 ratio (Mann-Withney test, n = 117). (E, F) Correlation between leptin levels (A) or BMI (C) and ALSFRS-R slope, determined as the decline of the score over a period of six months starting at the point of blood collection. Correlation coefficients (r) are indicated. n.s., non-significant p-value (Spearman test, n = 111). (G, H) Kaplan-Meier curves of survival in patients with low or high leptin levels, and in patients with low or high BMI, according to the median values of the population. Survival was the interval between the point of blood collection and death. n.s., non-significant p-value (Gehan-Breslow-Wilcoxon test, n = 117).

Mentions: High SCD index is often associated with metabolic conditions characterized by high BMI. Therefore, we asked whether other markers of global adiposity, such as BMI and leptin concentration [29], measured at the same time as the 16:1/16:0 ratio, could predict survival. Patients with a 16:1/16:0 ratio above the median of the ALS population had significantly higher leptin levels and BMI than patients with lower 16:1/16:0 ratios (Fig 3A and 3B). No differences in BMI or leptin concentrations were observed between patients when considering the 18:1/18:0 ratio (Fig 3C and 3D). Despite the relationship between 16:1/16:0 ratio and such fat tissue proxies, BMI or circulating leptin content did not correlate with ALSFRS-R decline, nor prognosticated survival based on multivariate analysis (Fig 3E–3H). Only when using univariate analysis, BMI was able to predict survival (HR = 0.12, 95%CI = 0.02–0.78, p = 0.025).


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)

Blood cell 16:1/16:0 ratio is associated with leptin levels and BMI.Circulating amounts of leptin (A, C) and BMI (B, D) in patients with low or high 16:1/16:0 ratio, and in patients with low or high 18:1/18:0 ratio (Mann-Withney test, n = 117). (E, F) Correlation between leptin levels (A) or BMI (C) and ALSFRS-R slope, determined as the decline of the score over a period of six months starting at the point of blood collection. Correlation coefficients (r) are indicated. n.s., non-significant p-value (Spearman test, n = 111). (G, H) Kaplan-Meier curves of survival in patients with low or high leptin levels, and in patients with low or high BMI, according to the median values of the population. Survival was the interval between the point of blood collection and death. n.s., non-significant p-value (Gehan-Breslow-Wilcoxon test, n = 117).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0131512.g003: Blood cell 16:1/16:0 ratio is associated with leptin levels and BMI.Circulating amounts of leptin (A, C) and BMI (B, D) in patients with low or high 16:1/16:0 ratio, and in patients with low or high 18:1/18:0 ratio (Mann-Withney test, n = 117). (E, F) Correlation between leptin levels (A) or BMI (C) and ALSFRS-R slope, determined as the decline of the score over a period of six months starting at the point of blood collection. Correlation coefficients (r) are indicated. n.s., non-significant p-value (Spearman test, n = 111). (G, H) Kaplan-Meier curves of survival in patients with low or high leptin levels, and in patients with low or high BMI, according to the median values of the population. Survival was the interval between the point of blood collection and death. n.s., non-significant p-value (Gehan-Breslow-Wilcoxon test, n = 117).
Mentions: High SCD index is often associated with metabolic conditions characterized by high BMI. Therefore, we asked whether other markers of global adiposity, such as BMI and leptin concentration [29], measured at the same time as the 16:1/16:0 ratio, could predict survival. Patients with a 16:1/16:0 ratio above the median of the ALS population had significantly higher leptin levels and BMI than patients with lower 16:1/16:0 ratios (Fig 3A and 3B). No differences in BMI or leptin concentrations were observed between patients when considering the 18:1/18:0 ratio (Fig 3C and 3D). Despite the relationship between 16:1/16:0 ratio and such fat tissue proxies, BMI or circulating leptin content did not correlate with ALSFRS-R decline, nor prognosticated survival based on multivariate analysis (Fig 3E–3H). Only when using univariate analysis, BMI was able to predict survival (HR = 0.12, 95%CI = 0.02–0.78, p = 0.025).

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