The polymorphism T1470A of the SLC16A1 gene is associated with the lactate and ventilatory thresholds but not with fat oxidation capacity in young men.

PURPOSE: To examine the association of the single nucleotide polymorphism A1470T in the SLC16A1 gene with blood lactate accumulation during a graded exercise test and its associated metaboreflex. METHODS: Forty-six Latin-American men (Age: 27 ± 6 years; Body fat: 17.5 ± 4.7%) performed a graded exercise test on a treadmill for the assessment of maximal oxygen uptake (VO2max), lactate threshold (LT), ventilatory threshold (VT) and the exercise intensity corresponding to maximal fat oxidation rate (FATmax), via capillary blood samples and indirect calorimetry. Genomic DNA was extracted from a peripheral blood sample. Genotyping assay was carried out by real-time polymerase chain reaction to identify the A1470T polymorphism (rs1049434). RESULTS: Genotypes distribution were in Hardy-Weinberg equilibrium (X2 = 5.6, p > 0.05), observing allele frequencies of 0.47 and 0.53 for the A and T alleles, respectively. No difference in VO2max, body composition nor FATmax were observed across genotypes, whereas carriers of the TT genotype showed a higher LT (24.5 ± 2.2 vs. 15.6 ± 1.7 mL kg-1 min-1, p < 0.01) and VT in comparison to carriers of the AA + AT genotypes (32.5 ± 3.3 vs. 21.7 ± 1.5 mL kg-1 min-1, p < 0.01). Both, VO2max and the A1470T polymorphism were positively associated to the LT (R2 = 0.50, p < 0.01) and VT (R2 = 0.55, p < 0.01). Only VO2max was associated to FATmax (R2 = 0.39, p < 0.01). CONCLUSION: Independently of cardiorespiratory fitness, the A1470T polymorphism is associated to blood lactate accumulation and its associated ventilatory response during submaximal intensity exercise. However, the A1470 polymorphism does not influence fat oxidation capacity during exercise in young men.

Exercise Fat Oxidation Is Positively Associated with Body Fatness in Men with Obesity: Defying the Metabolic Flexibility Paradigm.

Obesity is thought to be associated with a reduced capacity to increase fat oxidation in response to physical exercise; however, scientific evidence supporting this paradigm remains scarce. This study aimed to determine the interrelationship of different submaximal exercise metabolic flexibility (Metflex) markers and define its association with body fatness on subjects with obesity. Twenty-one male subjects with obesity performed a graded-intensity exercise protocol (Test 1) during which cardiorespiratory fitness (CRF), maximal fat oxidation (MFO) and its corresponding exercise intensity (FATmax) were recorded. A week afterward, each subject performed a 60-min walk (treadmill) at FATmax (Test 2), and the resulting fat oxidation area under the curve (TFO) and maximum respiratory exchange ratio (RERpeak) were recorded. Blood lactate (LAb) levels was measured during both exercise protocols. Linear regression analysis was used to study the interrelationship of exercise Metflex markers. Pearson's correlation was used to evaluate all possible linear relationships between Metflex and anthropometric measurement, controlling for CRF). The MFO explained 38% and 46% of RERpeak and TFO's associated variance (p < 0.01) while TFO and RERpeak were inversely related (R2 = 0.54, p < 0.01). Body fatness positively correlated with MFO (r = 0.64, p < 0.01) and TFO (r = 0.63, p < 0.01) but inversely related with RERpeak (r = -0.67, p < 0.01). This study shows that MFO and RERpeak are valid indicators of TFO during steady-state exercise at FATmax. The fat oxidation capacity is directly associated with body fatness in males with obesity.

The Increased Expression of Regulator of G-Protein Signaling 2 (RGS2) Inhibits Insulin-Induced Akt Phosphorylation and Is Associated with Uncontrolled Glycemia in Patients with Type 2 Diabetes.

Experimental evidence in mice models has demonstrated that a high regulator of G-protein signaling 2 (RSG2) protein levels precede an insulin resistance state. In the same context, a diet rich in saturated fatty acids induces an increase in RGS2 protein expression, which has been associated with decreased basal metabolism in mice; however, the above has not yet been analyzed in humans. For this reason, in the present study, we examined the association between RGS2 expression and insulin resistance state. The incubation with palmitic acid (PA), which inhibits insulin-mediated Akt Ser473 phosphorylation, resulted in the increased RGS2 expression in human umbilical vein endothelial-CS (HUVEC-CS) cells. The RGS2 overexpression without PA was enough to inhibit insulin-mediated Akt Ser473 phosphorylation in HUVEC-CS cells. Remarkably, the platelet RGS2 expression levels were higher in type 2 diabetes mellitus (T2DM) patients than in healthy donors. Moreover, an unbiased principal component analysis (PCA) revealed that RGS2 expression level positively correlated with glycated hemoglobin (HbA1c) and negatively with age and high-density lipoprotein cholesterol (HDL) in T2DM patients. Furthermore, PCA showed that healthy subjects segregated from T2DM patients by having lower levels of HbA1c and RGS2. These results demonstrate that RGS2 overexpression leads to decreased insulin signaling in a human endothelial cell line and is associated with poorly controlled diabetes.