Citations

A pulse ([14C]palmitate)-chase ([3H]palmitate) approach was used to study intramuscular triglyceride (imTG) fatty acid and plasma free fatty acid (FFA) kinetics during exercise at ∼45% peak O2consumption in 12 adults. Vastus lateralis muscle was biopsied before and after 90 min of bicycle exercise;3H2O production, breath14CO2excretion and lipid oxidation (indirect calorimetry) rates were measured during exercise. Results: during exercise, 8.2 ± 1.2 and 8.4 ± 0.7 μmol · kg−1· min−1of imTG fatty acids and plasma FFA, respectively, were oxidized according to isotopic measurements. The sum of these two values was not different ( P = 0.6) from lipid oxidation by indirect calorimetry (15.4 ± 1.6 μmol · kg−1· min−1); the isotopic and indirect calorimetry values were correlated ( r = 0.79, P < 0.005). During exercise, imTG turnover rate was 0.32 ± 0.07%/min (6.0 ± 2.0 μmol of imTG · kg wet muscle−1· min−1) and plasma FFA were incorporated into imTG at a rate of 0.7 ± 0.1 μmol · kg wet muscle−1· min−1. The imTG pool size did not change during exercise. This pulse-chase, dual tracer appears to be a reasonable approach to measure oxidation and synthesis kinetics of imTG.

We examined the relationship between energy expenditure (in kcal) and epinephrine (Epi), norepinephrine (NE), and growth hormone (GH) release. Ten men [age, 26 yr; height, 178 cm; weight, 81 kg; O2uptake at lactate threshold (LT), 36.3 ml · kg−1 · min−1; peak O2uptake, 49.5 ml · kg−1 · min−1] were tested on six randomly ordered occasions [control, 5 exercise: at 25 and 75% of the difference between LT and rest (0.25LT, 0.75LT), at LT, and at 25 and 75% of the difference between LT and peak (1.25LT, 1.75LT) (0900–0930)]. From 0700 to 1300, blood was sampled and assayed for GH, Epi, and NE. Carbohydrate (CHO) expenditure during exercise and fat expenditure during recovery rose proportionately to increasing exercise intensity ( P = 0.002). Fat expenditure during exercise and CHO expenditure during recovery were not affected by exercise intensity. The relationship between exercise intensity and CHO expenditure during exercise could not be explained by either Epi ( P = 1.00) or NE ( P = 0.922), whereas fat expenditure during recovery increased with Epi and GH independently of exercise intensity ( P = 0.028). When Epi and GH were regressed against fat expenditure during recovery, only GH remained statistically significant ( P < 0.05). We conclude that a positive relationship exists between exercise intensity and both CHO expenditure during exercise and fat expenditure during recovery and that the increase in fat expenditure during recovery with higher exercise intensities is related to GH release.

We evaluated the applicability of stable isotopic tracers to the study of intramuscular fatty acid metabolism by infusing both [U-13C]palmitate and [1-13C]oleate intravenously for 4 h into fasted conscious rats. Skeletal muscles were sequentially biopsied, and the concentration and13C enrichment of fatty acids were measured by gas chromatography/combustion/isotope ratio mass spectrometry. Throughout the study, the13C enrichment of plasma palmitate and oleate remained substantially greater than intramuscular nonesterified palmitate and oleate enrichment, which in turn was greater than intramuscular triglyceride palmitate and oleate enrichment. Fractional synthesis rates of intramuscular triglycerides in gastrocnemius and soleus were 0.267 ± 0.075 and 0.100 ± 0.030/h ( P = 0.04), respectively, as determined by using [U-13C]palmitate, and were 0.278 ± 0.049 and 0.075 ± 0.013/h ( P = 0.02), respectively, by using [1-13C]oleate. We conclude that plasma free fatty acids are a source for intramuscular triglycerides and nonesterified fatty acids; the latter are likely the synthetic precursors of the former. Uniformly and singly labeled [13C]fatty acid tracers will provide an important tool to study intramuscular fatty acid and triglyceride metabolism.

To determine the source(s) of blood and very low density lipoprotein (VLDL)-triglyceride glycerol during fasting, four men ingested2H2O from 14 to 20 h into a 60-h fast to achieve ∼0.5% body water enrichment. At 60 h of fasting, glycerol flux was measured using [2-14C]glycerol. Blood was taken for measurement of2H enrichment at carbon 6 of glucose and at carbon 3 of free glycerol and VLDL-triglyceride glycerol.2H enrichment of the 2 hydrogens bound to carbon 3 of VLDL-triglyceride glycerol was 105 ± 2% of the2H enrichment of the 2 hydrogens bound to carbon 6 of glucose, indicating isotopic equilibrium between hepatic glyceraldehyde 3- P and glycerol 3- P. The2H enrichment of the 2 hydrogens bound to carbon 3 of free glycerol was 17 ± 3% of VLDL-triglyceride glycerol, indicating that a significant percentage of free glycerol in blood originated from the hydrolysis of circulating VLDL-triglyceride or a pool of glycerol with similar2H enrichment. Glycerol flux was 6.3 ± 1.1 μmol · kg−1· min−1. Glycerol appearing from nonadipose tissue sources was then ∼1.1 μmol · kg−1· min−1. Seven other subjects were fasted for 12, 42, and 60 h. A small percentage of glycerol in the circulation after 12 h of fasting was enriched with2H. The enrichment of the 2 hydrogens bound to carbon 3 of free glycerol in the longer periods of fasting was ∼16% of the enrichment of the 2 hydrogens bound to carbon 6 of glucose. Therefore, as much as 15–20% of systemic glycerol turnover during fasting is not from lipolysis of adipose tissue triglyceride.

These studies were conducted to understand the relationship between measures of systemic free fatty acid (FFA) reesterification and regional FFA, glycerol, and triglyceride metabolism during fasting. Indirect calorimetry was used to measure fatty acid oxidation in six men after a 60-h fast. Systemic and regional (splanchnic, renal, and leg) FFA ([3H]palmitate) and glycerol ([3H]glycerol) kinetics, as well as splanchnic triglyceride release, were measured. The rate of systemic FFA reesterification was 366 ± 93 μmol/min, which was greater ( P < 0.05) than splanchnic triglyceride fatty acid output (64 ± 6 μmol/min), a measure of VLDL triglyceride fatty acid export. The majority of glycerol uptake occurred in the splanchnic and renal beds, although some leg glycerol uptake was detected. Systemic FFA release was approximately double that usually present in overnight postabsorptive men, yet the regional FFA release rates were of the same proportions previously observed in overnight postabsorptive men. In conclusion, FFA reesterification at rest during fasting far exceeds splanchnic triglyceride fatty acid output. This indicates that nonhepatic sites of FFA reesterification are important, and that peripheral reesterification of FFA exceeds the rate of simultaneous intracellular triglyceride fatty acid oxidation.

To determine whether type 2 diabetes mellitus alters systemic and regional free fatty acid ([3H]palmitate) metabolism, 14 nondiabetic (ND) and 14 type 2 diabetic (D) subjects underwent hyperinsulinemic-hyperglycemic (∼9.3 mM) clamps. The subjects were matched for age, body mass index, percent body fat, and fat-free mass. D subjects had more ( P < 0.05) visceral fat than ND. During somatostatin, replacement growth hormone, and glucagon infusions, insulin was infused to achieve moderate (∼75 pmol/l) and high (∼150 pmol/l) physiological insulin levels. D subjects had greater ( P < 0.02) systemic and regional (splanchnic and leg) palmitate release than ND subjects during both insulin infusion intervals. The relative contributions of splanchnic, leg, and nonsplanchnic upper body regions to systemic palmitate release did not differ between groups, although the last contributed the most (∼75%) to systemic palmitate release. Visceral fat area correlated with systemic palmitate flux ( r = 0.45, P < 0.03) during both insulin infusions. We conclude that type 2 diabetes is associated with a generalized impairment in insulin suppression of lipolysis compared with equally obese ND individuals.

Dual-energy X-ray absorptiometry (DEXA) is reported to be inferior to computed tomography (CT) to measure changes in appendicular soft tissue composition. We compared CT- and DEXA-measured thigh muscle and fat mass to evaluate the random and systematic discrepancies between these two methods. Thigh skeletal muscle area (single-slice CT) was suboptimally ( r2= 0.74, P < 0.0001) related to DEXA-measured thigh fat-free mass (FFM). In contrast, thigh muscle and adipose tissue volumes (multislice CT) were highly related to DEXA-measured thigh FFM and fat (both r2= 0.96, P < 0.0001). DEXA-measured leg fat was significantly less than multislice-CT-measured leg adipose tissue volume, whereas multislice-CT-measured leg muscle mass was less ( P < 0.0001) than DEXA-measured leg FFM. The systematic discrepancies between the two approaches were consistent with the 10–15% nonfat components of adipose tissue. In conclusion, CT and DEXA measures of appendicular soft tissue are highly related. Systematic differences between DEXA and CT likely relate to the underlying principles of the techniques.

Jensen, Michael D., Tu T. Nguyen, A. Hernández Mijares, C. Michael Johnson, and Michael J. Murray. Effects of gender on resting leg blood flow: implications for measurement of regional substrate oxidation. J. Appl. Physiol. 84(1): 141–145, 1998.—These studies were designed to examine whether the respiratory quotient (RQ) of leg tissue (primarily skeletal muscle) would increase to a greater degree in women than in men during meal ingestion. We found that mean leg and systemic RQ values were similar in men under both basal and fed conditions, whereas the agreement was poor in women. In women, leg RQ values tended to be greater than the systemic RQ, whereas splanchnic RQ values tended to be lower than the systemic RQ. The possibility that measurement imprecision accounted for the different findings in women could not be excluded because the arteriovenous blood O2 differences were almost twice as great in men as in women (53.7 ± 5.4 vs. 28.6 ± 2.9 ml of O2/l, respectively; P < 0.01), as were venoarterial blood CO2 differences. The smaller arteriovenous differences in women appeared to limit our ability to accurately measure their leg RQ values. O2 uptake relative to leg fat-free mass (FFM) was not different between men and women, whereas leg blood flow relative to leg FFM was greater in women than in men (55 ± 3 vs. 39 ± 2 ml ⋅ kg FFM−1 ⋅ min−1, respectively; P < 0.001). These findings were confirmed by examining data from other studies conducted in our laboratory to create a larger data set. We conclude that resting leg blood flow in women is greater (relative to FFM) than in men, making it more difficult to accurately measure leg RQ in women.

During running exercise above the lactate threshold (LT), it is unknown whether free fatty acid (FFA) mobilization can meet the energy demands for fatty acid oxidation. This study was performed to determine whether FFA availability is reduced during running exercise above compared with below the LT and to assess whether the level of endurance training influences FFA mobilization. Twelve marathon runners and 12 moderately trained runners ran at a workload that was either above or below their individual LT. Fatty acid oxidation (indirect calorimetry) and FFA release ([1–14C]palmitate) were measured at baseline, throughout exercise, and at recovery. The plasma FFA rate of appearance increased during exercise in both groups; running above or below the LT, but the total FFA availability for 30 min of exercise was greater (P < 0.01) in the below LT group (marathon, 23 +/- 2 mmol; moderate, 21 +/- 2 mmol) than in the above LT group (18 +/- 3 and 13 +/- 3 mmol, respectively). Total fatty acid oxidation (indirect calorimetry) greatly exceeded circulating FFA availability, regardless of training or exercise group (P < 0.01). No statistically significant exercise intensity or training differences in fatty acid oxidation were found (above LT: marathon, 71 +/- 12, moderate, 64 +/- 17 mmol/30 min; below LT: marathon 91 +/- 12, moderate, 60 +/- 5 mmol/30 min). In conclusion, during exercise above or below LT, circulating FFA cannot meet the oxidative needs and intramuscular triglyceride stores must be utilized. Further marathon training does not enhance effective adipose tissue lipolysis during exercise compared with moderate endurance training.