Jill A. Fattor

Lactate and glucose interactions during rest and exercise in men: effect of exogenous lactate infusion

To test the hypothesis that lactate plays a central role in the distribution of carbohydrate (CHO) potential energy for oxidation and glucose production (GP), we performed a lactate clamp (LC) procedure during rest and moderate intensity exercise. Blood [lactate] was clamped at ≈4 mm by exogenous lactate infusion. Subjects performed 90 min exercise trials at 65 % of the peak rate of oxygen consumption (V̇O2,peak; 65 %), 55 % V̇O2,peak (55 %) and 55 % V̇O2,peak with lactate clamped to the blood [lactate] that was measured at 65 % V̇O2,peak (55 %‐LC). Lactate and glucose rates of appearance (Ra), disappearance (Rd) and oxidation (Rox) were measured with a combination of [3‐13C]lactate, H13CO3−, and [6,6‐2H2]glucose tracers. During rest and exercise, lactate Ra and Rd were increased at 55 %‐LC compared to 55 %. Glucose Ra and Rd were decreased during 55 %‐LC compared to 55 %. Lactate Rox was increased by LC during exercise (55 %: 6.52 ± 0.65 and 55 %‐LC: 10.01 ± 0.68 mg kg−1 min−1) which was concurrent with a decrease in glucose oxidation (55 %: 7.64 ± 0.4 and 55 %‐LC: 4.35 ± 0.31 mg kg−1 min−1). With LC, incorporation of 13C from tracer lactate into blood glucose (L → GNG) increased while both GP and calculated hepatic glycogenolysis (GLY) decreased. Therefore, increased blood [lactate] during moderate intensity exercise increased lactate oxidation, spared blood glucose and decreased glucose production. Further, exogenous lactate infusion did not affect rating of perceived exertion (RPE) during exercise. These results demonstrate that lactate is a useful carbohydrate in times of increased energy demand.

Lipolysis and fatty acid metabolism in men and women during the postexercise recovery period

We sought to determine whether lipolysis, fatty acid (FA) mobilization, and plasma FA oxidation would remain elevated for hours following isoenergetic exercise bouts of different intensities. Ten men and eight women received a primed‐continuous infusion of [1,1,2,3,3‐2H5]glycerol and continuous infusion of [1‐13C]palmitate to measure glycerol and plasma FA kinetics. On Day 1 (D1), participants were studied under one of three different conditions, assigned in random order: (1) before, during and 3 h after 90 min of exercise at 45% (E45), (2) before, during and 3 h after 60 min of exercise at 65% (E65), and (3) in a time‐matched sedentary control trial (C). For each condition, participants were studied by indirect calorimetry the following morning as well (D2). Rate of appearance (Ra) of glycerol (RaGL) increased above C during exercise in men and women (P < 0.05), was higher in E45 than E65 in men (P < 0.05), and was not different between exercise intensities in women. During 3 h of postexercise recovery, RaGL remained significantly elevated in men (P < 0.05), but not women. FA Ra (RaFA) increased during exercise in men and women and was higher in E45 than E65 (P < 0.05), and remained elevated during 3 h of postexercise recovery in both sexes (P < 0.05), but with a greater relative increase in men than women (P < 0.05). Plasma FA oxidation (Rox) increased during exercise with no difference between intensities, and it remained elevated during 3 h of postexercise recovery in both sexes (P < 0.05). Total lipid oxidation (Lox) was elevated in both sexes (P < 0.05), but more in men during 3 h of postexercise recovery on D1 (P < 0.05) and remained elevated on D2 in men (P < 0.05), but not in women. There were no differences between E45 and E65 for postexercise energy substrate turnover or oxidation in men and women as energy expenditure of exercise (EEE) was matched between bouts. We conclude that the impact of exercise upon lipid metabolism persists into recovery, but that women depend more on lipid during exercise whereas, during recovery, lipid metabolism is accentuated to a greater extent in men.

Lactate kinetics at the lactate threshold in trained and untrained men

To understand the meaning of the lactate threshold (LT) and to test the hypothesis that endurance training augments lactate kinetics [i.e., rates of appearance and disposal (Ra and Rd, respectively, mg·kg(-1)·min(-1)) and metabolic clearance rate (MCR, ml·kg(-1)·min(-1))], we studied six untrained (UT) and six trained (T) subjects during 60-min exercise bouts at power outputs (PO) eliciting the LT. Trained subjects performed two additional exercise bouts at a PO 10% lower (LT-10%), one of which involved a lactate clamp (LC) to match blood lactate concentration ([lactate]b) to that achieved during the LT trial. At LT, lactate Ra was higher in T (24.1 ± 2.7) than in UT (14.6 ± 2.4; P < 0.05) subjects, but Ra was not different between UT and T when relative exercise intensities were matched (UT-LT vs. T-LT-10%, 67% Vo2max). At LT, MCR in T (62.5 ± 5.0) subjects was 34% higher than in UT (46.5 ± 7.0; P < 0.05), and a reduction in PO resulted in a significant increase in MCR by 46% (LT-10%, 91.5 ± 14.9, P < 0.05). At matched relative exercise intensities (67% Vo2max), MCR in T subjects was 97% higher than in UT (P < 0.05). During the LC trial, MCR in T subjects was 64% higher than in UT (P < 0.05), in whom %Vo2max and [lactate]b were similar. We conclude that 1) lactate MCR reaches an apex below the LT, 2) LT corresponds to a limitation in MCR, and 3) endurance training augments capacities for lactate production, disposal and clearance.

Gluconeogenesis and hepatic glycogenolysis during exercise at the lactate threshold

Because the maintenance of glycemia is essential during prolonged exercise, we examined the effects of endurance training, exercise intensity, and plasma lactate concentration ([lactate]) on gluconeogenesis (GNG) and hepatic glycogenolysis (GLY) in fasted men exercising at, and just below, the lactate threshold (LT), where GNG precursor lactate availability is high. Twelve healthy men (6 untrained, 6 trained) completed 60 min of constant-load exercise at power outputs corresponding to their individual LT. Trained subjects completed two additional 60-min sessions of constant-load exercise: one at 10% below the LT workload (LT-10%), and the other with a lactate clamp (LT-10%+LC) to match the [lactate] of the LT trial. Flux rates were determined by primed continuous infusion of [6,6-(2)H(2)]glucose, [3-(13)C]lactate, and [(13)C]bicarbonate tracers during 90 min of rest and 60 min of cycling. Exercise at LT corresponded to 67.6 ± 1.3 and 74.8 ± 1.7% peak O(2) consumption in the untrained and trained subjects, respectively (P < 0.05). Relative exercise intensity was matched between the untrained group at LT and the trained group at LT-10%, and [lactate] during exercise was matched in the LT and LT-10%+LC trials via exogenous lactate infusion. Glucose kinetics (rate of appearance, rate of disposal, and metabolic clearance rate) were augmented with the lactate clamp. GNG was decreased in the trained subjects exercising at LT and LT-10% compared with the untrained subjects, but increasing [lactate] in the LT-10%+LC trial significantly increased GNG (4.4 ± 0.9 mg·kg(-1)·min(-1)) compared with its corresponding control (1.7 ± 0.4 mg·kg(-1)·min(-1), P < 0.05). Hepatic GLY was higher in the trained than untrained subjects, but not significantly different across conditions. We conclude that GNG plays an essential role in maintaining total glucose production during exercise in fasted men, regardless of training state. However, endurance training increases the ability to achieve a higher relative exercise intensity and absolute power output at the LT without a significant decrease in GNG. Furthermore, raising systemic precursor substrate availability increases GNG during exercise, but not at rest.

Direct and indirect lactate oxidation in trained and untrained men

Lactate has been shown to be an important oxidative fuel. We aimed to quantify the total lactate oxidation rate (Rox) and its direct vs. indirect (glucose that is gluconeogenically derived from lactate and subsequently oxidized) components (mg·kg(-1)·min(-1)) during rest and exercise in humans. We also investigated the effects of endurance training, exercise intensity, and blood lactate concentration ([lactate]b) on direct and indirect lactate oxidation. Six untrained (UT) and six trained (T) men completed 60 min of constant load exercise at power outputs corresponding to their lactate threshold (LT). T subjects completed two additional 60-min sessions of constant load exercise at 10% below the LT workload (LT-10%), one of which included a lactate clamp (LC; LT-10%+LC). Rox was higher at LT in T [22.7 ± 2.9, 75% peak oxygen consumption (Vo2peak)] compared with UT (13.4 ± 2.5, 68% Vo2peak, P < 0.05). Increasing [lactate]b (LT-10%+LC, 67% Vo2peak) significantly increased lactate Rox (27.9 ± 3.0) compared with its corresponding LT-10% control (15.9 ± 2.2, P < 0.05). Direct and indirect Rox increased significantly from rest to exercise, and their relative partitioning remained constant in all trials but differed between T and UT: direct oxidation comprised 75% of total lactate oxidation in UT and 90% in T, suggesting the presence of training-induced adaptations. Partitioning of total carbohydrate (CHO) use showed that subjects derived one-third of CHO energy from blood lactate, and exogenous lactate infusion increased lactate oxidation significantly, causing a glycogen-sparing effect in exercising muscle.

Effects of Endurance Training on Cardiorespiratory Fitness and Substrate Partitioning in Postmenopausal Women

We examined the effect of endurance training on energy substrate partitioning during rest and exercise in postmenopausal women. Ten healthy sedentary (55 +/- 1 years old) subjects completed 12 weeks of endurance exercise training on a cycle ergometer (5 d/wk, 1 h/d, 65% peak oxygen consumption [Vo(2)peak]). Whole-body energy substrate oxidation was determined by indirect calorimetry during 90 minutes of rest and 60 minutes of cycle ergometer exercise. Subjects were studied at 65% Vo(2)peak before training and after training at the same absolute exercise intensity (same absolute workload as 65% of pretraining Vo(2)peak) and same relative exercise intensity (65% of posttraining Vo(2)peak). After training, Vo(2)peak increased by 16.3% +/- 3.9% and resting heart rate decreased by 4 beats per minute (P < .05). During exercise at same absolute intensity, mean arterial pressure decreased by 8 mm Hg (P < .05), heart rate decreased by 19 beats per minute (P < .05), energy derived from carbohydrate decreased by 9.6%, and the energy derived from lipid increased by 9.2% (P < .05). Lactate concentration was lower at the same absolute and relative exercise intensities (P < .05). Changes in substrate partitioning during exercise were accomplished without changes in dietary composition, body weight, or body composition. We conclude that endurance training in healthy postmenopausal women who remain in energy balance results in many of the classic cardiopulmonary training effects, decreases the reliance on carbohydrate, and increases lipid oxidation during a given submaximal exercise task without a reduction in body weight.

Training improves the response in glucose flux to exercise in postmenopausal women

We examined the effects of endurance training on parameters of glucose flux during rest and exercise in postmenopausal women. Ten sedentary, but healthy women (55 +/- 1 yr) completed 12 wk of endurance exercise training on a cycle ergometer [5 days/wk, 1 h/day, 65% peak oxygen consumption (Vo(2peak))]. Flux rates were determined by primed continuous infusion of [6,6-(2)H]glucose (D(2)-glucose) during 90 min of rest and 60 min of cycle ergometer exercise during one pretraining exercise trial [65% Vo(2peak) (PRE)] and two posttraining exercise trials [the power output that elicited 65% pretraining Vo(2peak) (ABT) and 65% posttraining Vo(2peak) (RLT)]. Training increased Vo(2peak) by 16.3 +/- 3.9% (P < 0.05). Epinephrine and glucagon were lower during ABT and lactate was lower during ABT and RLT (P < 0.05), but the apparent insulin response was unchanged. Whole body glucose rate of appearance decreased posttraining during exercise at a given power output (4.58 +/- 0.39 mg.kg(-1).min(-1) during ABT compared with 5.21 +/- 0.48 mg.kg(-1).min(-1) PRE, P < 0.05), but not at the same relative workload (5.85 +/- 0.36 mg.kg(-1).min(-1)). Training resulted in a 35% increase in glucose MCR during exercise at the same relative intensity (7.16 +/- 0.42 ml.kg(-1).min(-1) during RLT compared with 5.28 +/- 0.42 ml.kg(-1).min(-1) PRE, P < 0.05). Changes in parameters of glucose kinetics during exercise were accomplished without changes in dietary composition, body weight, or body composition. We conclude that despite changes in the hormonal milieu that occur at menopause, endurance training results in a similar magnitude in training-induced alterations of glucose flux as seen previously in younger women.

Twelve weeks of endurance training increases FFA mobilization and reesterification in postmenopausal women

We examined the effects of exercise intensity and training on rates of lipolysis, plasma free fatty acid (FFA) appearance (R(a)), disappearance (R(d)), reesterification (R(s)), and oxidation (R(oxP)) in postmenopausal (PM) women. Ten sedentary but healthy women (55 ± 0.6 yr) completed 12 wk of supervised endurance exercise training on a cycle ergometer [5 days/wk, 1 h/day, 65% peak oxygen consumption (Vo(2peak))]. Flux rates were determined by continuous infusion of [1-(13)C]palmitate and [1,1,2,3,3-(2)H(5)]glycerol during 90 min of rest and 60 min of cycle ergometer exercise during one pretraining exercise trial [65% Vo(2peak) (PRE)] and two posttraining exercise trials [at power outputs that elicited 65% pretraining Vo(2peak) (absolute training; ABT) and 65% posttraining Vo(2peak) (relative training; RLT)]. Initial body weights (68.2 ± 4.5 kg) were maintained over the course of study. Training increased Vo(2peak) by 16.3 ± 3.9% (P < 0.05) (Zarins ZA, Wallis GA, Faghihnia N, Johnson ML, Fattor JA, Horning MA and Brooks GA. Metabolism 58: 9: 1338-1346, 2009). Glycerol R(a) and R(d) were elevated in the RLT trial (P < 0.05), but not the ABT trial after training. Rates of plasma FFA R(a), R(d), and R(oxP) were elevated during the ABT compared with PRE trial (P < 0.05). FFA R(s) accounted for most (50-70%) of R(d) during exercise; training reduced FFA R(s) during ABT, but not RLT compared with PRE. We conclude that, despite the large age-related decrease in metabolic scope in PM women, endurance training increases the capacities for FFA mobilization and oxidation during exercises of a given power output. However, after menopause, total lipid oxidation capacity remains low, with reesterification accounting for most of FFA R(d).

Cyclic Hypobaric Hypoxia Improves Markers of Glucose Metabolism in Middle-Aged Men

UNLABELLED Chronic hypoxia increases dependence on glucose in men and increases insulin sensitivity in men and women. Cyclic Variations in Altitude Conditioning (CVAC) is a novel technology that provides exposure to rapidly fluctuating cyclic hypobaric hypoxia (CHH). PURPOSE To test the hypothesis that markers of glucose metabolism would change with CVAC CHH, two groups of middle-aged men were exposed to 10 weeks (40 min/day, 3 day/week) of either CHH or sham (SH) sessions. METHODS CHH subjects (age: 48 ± 6, weight: 86 ± 12 kg, BMI: 27.1 ± 3, n=11) experienced cyclic pressures simulating altitudes ranging from sea level to 3048 m (week 1) and progressing to 6096 m (by week 5 through week 10). SH subjects (age: 50 ± 4, weight: 89 ± 15 kg, BMI: 27.5 ± 3, n=10) were exposed to slowly-fluctuating pressures up to 607 m (all subjects blinded to elevation). Physical function and blood markers of glucose metabolism were measured at baseline, 3, 6, and 10 weeks. RESULTS Two CHH subjects were dropped from analysis for failure to progress past 3048 m (CHH: n=9). Weight and physical activity remained stable for both groups. There was a group-by-time interaction in fasting glucose (CHH: 96 ± 9 to 91 ± 7 mg/dL, SH: 94 ± 7 to 97 ± 9 mg/dL, p<0.05). Reduction in plasma glucose response to oral glucose tolerance test [area under the curve] was greater in CHH compared to SH after 10 weeks of exposure (p<0.03). Neither group experienced changes in fasting insulin, insulin response during the OGTT, or changes in a timed walk test. CONCLUSION Ten weeks of CVAC CHH exposure improves markers of glucose metabolism in middle-aged men at risk for metabolic syndrome.

Catecholamine Response is Attenuated During Moderate Intensity Exercise in Response to the ???Lactate Clamp???.

Catecholamine release is known to be regulated by feedforward and feedback mechanisms. Norepinephrine (NE) and epinephrine (Epi) concentrations rise in response to stresses, such as exercise, that challenge blood glucose homeostasis. The purpose of this study was to assess the hypothesis that the lactate anion is involved in feedback control of catecholamine concentration. Six healthy active men (26 +/- 2 yr, 82 +/- 2 kg, 50.7 +/- 2.1 ml.kg(-1).min(-1)) were studied on five occasions after an overnight fast. Plasma concentrations of NE and Epi were determined during 90 min of rest and 90 min of exercise at 55% of peak O2 consumption (VO2 peak) two times with exogenous lactate infusion (lactate clamp, LC) and two times without LC (CON). The blood lactate profile ( approximately 4 mM) of a preliminary trial at 65% VO2 peak (65%) was matched during the subsequent LC trials. In resting men, plasma NE concentration was not different between trials, but during exercise all conditions were different with 65% > CON > LC (65%: 2,115 +/- 166 pg/ml, CON: 1,573 +/- 153 pg/ml, LC: 930 +/- 174 pg/ml, P < 0.05). Plasma Epi concentrations at rest were different between conditions, with LC less than 65% and CON (65%: 68 +/- 9 pg/ml, CON: 59 +/- 7 pg/ml, LC: 38 +/- 10 pg/ml, P < 0.05). During exercise, Epi concentration showed the same trend (65%: 262 +/- 37 pg/ml, CON: 190 +/- 34 pg/ml, LC: 113.2 +/- 23 pg/ml, P < 0.05). In conclusion, lactate attenuates the catecholamine response during moderate-intensity exercise, likely by feedback inhibition.