Higher D-lactate levels are associated with higher prevalence of small dense low-density lipoprotein in obese adolescents

Rodríguez-Mortera, Reyna; Luévano-Contreras, Claudia; Solorio-Meza, Sergio; Caccavello, Russell; Bains, Yasmin; Garay‐Sevilla, Ma. Eugenia; Gugliucci, Alejandro

doi:10.1515/cclm-2017-0733

Cited by 11 publications

(10 citation statements)

References 35 publications

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“…These findings are in line with the current literature suggestive of plasma D-lactate level as a surrogate marker for MG flux, which is increased in obesity (26,(32)(33)(34). Furthermore, in a cross-sectional study, we previously demonstrated that serum D-lactate levels were higher in obese Latino adolescents and correlated with serum triglycerides and small dense LDL levels (27). Therefore, the notion that MG might be a toxic intermediate that precipitates metabolic disease in humans needed to be explored in an intervention study.…”

Section: Discussionsupporting

confidence: 92%

“…Serum samples were ultra-filtered to eliminate interference by the reaction of serum LDH with L-lactate and then incubated at 37 °C, and the reaction was followed kinetically to achieve maximal sensitivity and linearity (26). The <10-kDa fractions were separated by ultrafiltration through 0.5 mL Amicon ultra centrifugal filters spun at 14,000g for 30 min in a refrigerated centrifuge at 4 °C; the ultrafiltrate was employed to measure D-lactate (27). The limit of detection was 1 µmol/L, and the reaction was linear up to 15 µmol/L.…”

Section: De Novo Lipogenesis Insulin Sensitivity and D-lactatementioning

confidence: 99%

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Isocaloric Fructose Restriction Reduces Serum d-Lactate Concentration in Children With Obesity and Metabolic Syndrome

Erkin-Cakmak

Bains

Caccavello

et al. 2019

The Journal of Clinical Endocrinology &Amp; Metabolism

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Objective: To investigate the link between dietary sugar consumption and two separate pathogenetic mechanisms associated with metabolic syndrome: de novo lipogenesis (DNL) and non-enzymatic glycation. Design and participants: We assessed changes in serum D-lactate (the detoxification endproduct of methylglyoxal) concentration in response to nine days of isocaloric fructose restriction in 20 children with obesity and metabolic syndrome, and examined correlations with changes in DNL, liver fat, insulin sensitivity and other metrics of hepatic metabolism. Interventions: Nine days of dietary sugar restriction, with substitution of equal amounts of refined starch. Main Outcome Measures: On day 0 and 10, children had lab evaluation of D-lactate levels and other analytes, and underwent oral glucose tolerance testing, magnetic resonance spectroscopy to quantify fat depots, and 13 C-acetate incorporation into triglyceride to measure DNL. Results: D-lactate was associated with baseline liver fat fraction (p<0.001) and visceral adipose tissue (p<0.001), but not with subcutaneous adipose tissue. At baseline, D-lactate was positively correlated with DNL-AUC (p=0.003), liver fat fraction (p=0.02), triglyceride (p=0.004) and triglyceride to HDL ratio (p=0.002). After nine days of isocaloric fructose restriction, serum Dlactate levels reduced by 50% (p<0.0001), and changes in D-lactate correlated with both changes in DNL-AUC, and measures of insulin sensitivity. Conclusion: Baseline correlation of D-lactate with DNL and measures of insulin sensitivity; and reduction in D-lactate following nine days of isocaloric fructose restriction suggest that DNL and non-enzymatic glycation are functionally linked via intermediary glycolysis in the pathogenesis

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Section: Discussionsupporting

confidence: 92%

Section: De Novo Lipogenesis Insulin Sensitivity and D-lactatementioning

confidence: 99%

Isocaloric Fructose Restriction Reduces Serum d-Lactate Concentration in Children With Obesity and Metabolic Syndrome

Erkin-Cakmak

Bains

Caccavello

et al. 2019

The Journal of Clinical Endocrinology &Amp; Metabolism

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“…A venous blood sample was obtained after twelve hours of fasting. Serum was processed the same day and used for the measurement of glucose and lipids using enzymatic methods as shown earlier [ 10 , 12 ]. All other biomarkers were measured by ELISA as follows: Human Hepcidin Quantikine ELISA Cat# DHP250 and Human IL-6 Quantikine ELISA Cat# D6050 were from R&D Systems, NE, Minneapolis, MN, USA.…”

Section: Methodsmentioning

confidence: 99%

Higher Hepcidin Levels in Adolescents with Obesity Are Associated with Metabolic Syndrome Dyslipidemia and Visceral Fat

et al. 2021

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Tightly regulated iron metabolism prevents oxidative stress. Hepcidin is a hormone that regulates iron flow in plasma; its production is induced by an iron overload and by inflammation. It inhibits iron entry into the circulation by blocking dietary absorption in the duodenum, the release of recycled iron from macrophages and the exit of stored iron from hepatocytes. Varied signals responding to iron stores, erythropoietic activity and host defense converge to regulate hepcidin production and thereby affect iron homeostasis. Although it is known that hepcidin increases when interleukin 6 (IL-6) increases, the relationship between hepcidin, dyslipidemia, insulin resistance (IR) and visceral adiposity index (VAI) in adolescents with obesity is unclear. In this cross-sectional study of 29 obese adolescents and 30 control subjects, we explored the difference of hepcidin, iron metabolism markers and IL-6 between obese and non-obese adolescents, and identified associations with inflammation, atherogenic dyslipidemia and IR. As compared to lean controls, obese participants showed 67% higher hepcidin: 14,070.8 ± 7213.5 vs. 8419.1 ± 4826.1 pg/mLc; 70% higher ferritin: 94.4 ± 82.4 vs. 55.1 ± 39.6 pg/mLa and 120% higher IL-6: 2.0 (1.1–4.9) vs. 0.9 (0.5–1.3) pg/mLd. Transferrin, soluble transferrin receptor and total body iron (as measured by sTFR/ferritin, log10 sTFR/ferritin ratio and sTFR/log ferritin ratios) were not different between the two cohorts. In the whole cohort, hepcidin correlated with VAI (r = 0.29a), sd-LDL (r = 0.31b), HOMA-IR (r = 0.29a) and IL-6 (r = 0.35c). In obese adolescents hepcidin correlated with TG (r = 0.47b), VLDL-C (r = 0.43b) and smaller LDL2 (r = 0.39a). Hepcidin elevation in adolescents with obesity is linked more to inflammation and metabolic alterations than to iron metabolism since the other markers of iron metabolism were not different between groups, except for ferritin. Studies addressing the long-term effects of higher hepcidin levels and their impact on subclinical anemia and iron status are warranted. a p < 0.05; b p < 0.01, c p < 0.001 dp < 0.0001.

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“…Además, se ha propuesto que ese mismo aumento en el flujo de triosas también aumenta la generación de metilglioxal (MG), un dicarbonilo muy tóxico y su producto de desintoxicación, D-lactato (28,29) . El estrés de dicarbonilo promovido por el MG (que daña muchas proteínas) puede desempeñar un papel importante en el desarrollo del síndrome metabólico (30) .…”

Section: Fructosa Y Glucosa: La Gran Diferencia (Figuras 2 Y 3)unclassified

“…El estrés de dicarbonilo promovido por el MG (que daña muchas proteínas) puede desempeñar un papel importante en el desarrollo del síndrome metabólico (30) . Hemos mostrado que en adolescentes obesos, el D-lactato es 40% más alto que en los de peso normal, se asocia con dislipidemia y que la restricción de fructosa lo reduce en paralelo con la reducción de la lipogénesis y la grasa hepática (29,31) . Por lo tanto, propusimos que la fructosa puede jugar un papel clave en la obesidad y el síndrome metabólico por este nuevo mecanismo que se agrega a los descritos previamente.…”

Section: Fructosa Y Glucosa: La Gran Diferencia (Figuras 2 Y 3)unclassified

Fructosa, un factor clave modificable en la patogenia del síndrome metabólico, la esteatosis hepática y la obesidad

Gugliucci

Rodríguez-Mortera

2020

RMU

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Higher D-lactate levels are associated with higher prevalence of small dense low-density lipoprotein in obese adolescents

Cited by 11 publications

References 35 publications

Isocaloric Fructose Restriction Reduces Serum d-Lactate Concentration in Children With Obesity and Metabolic Syndrome

Isocaloric Fructose Restriction Reduces Serum d-Lactate Concentration in Children With Obesity and Metabolic Syndrome

Higher Hepcidin Levels in Adolescents with Obesity Are Associated with Metabolic Syndrome Dyslipidemia and Visceral Fat

Fructosa, un factor clave modificable en la patogenia del síndrome metabólico, la esteatosis hepática y la obesidad

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