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Very little is known about how metabolic health status, insulin resistance or metabolic challenges modulate the endocannabinoid (eCB) or polyunsaturated fatty acid (PUFA)-derived oxylipin (OxL) lipid classes. To address these questions, plasma eCB and OxL concentrations were determined at rest, 10 and 20 min during an acute exercise bout (30 min total, ~45% of preintervention V̇O2peak , ~63 W), and following 20 min recovery in overnight-fasted sedentary, obese, insulin-resistant women under controlled diet conditions. We hypothesized that increased fitness and insulin sensitivity following a ~14-week training and weight loss intervention would lead to significant changes in lipid signatures using an identical acute exercise protocol to preintervention. In the first 10 min of exercise, concentrations of a suite of OxL diols and hydroxyeicosatetraenoic acid (HETE) metabolites dropped significantly. There was no increase in 12,13-DiHOME, previously reported to increase with exercise and proposed to activate muscle fatty acid uptake and tissue metabolism. Following weight loss intervention, exercise-associated reductions were more pronounced for several linoleate and alpha-linolenate metabolites including DiHOMEs, DiHODEs, KODEs, and EpODEs, and fasting concentrations of 9,10-DiHODE, 12,13-DiHODE, and 9,10-DiHOME were reduced. These findings suggest that improved metabolic health modifies soluble epoxide hydrolase, cytochrome P450 epoxygenase (CYP), and lipoxygenase (LOX) systems. Acute exercise led to reductions for most eCB metabolites, with no evidence for concentration increases even at recovery. It is proposed that during submaximal aerobic exercise, nonoxidative fates of long-chain saturated, monounsaturated, and PUFAs are attenuated in tissues that are important contributors to the blood OxL and eCB pools.

Purpose: Walking net V ˙ O2 tends to increase with advancing age; however, factors contributing to this relationship have not been widely described. The implications of such findings could inform targeted strategies to promote independent mobility in older adults. Herein, we evaluated the relationship between net V ˙ O2 and age at two submaximal workloads while exploring potential moderators of this relationship. Methods: Secondary analyses were performed on 35 older (65 ± 3 years) women who completed a battery of physical assessments including fixed-speed, non-graded and graded (+ 2.5%) treadmill walking with indirect calorimetry to determine net V ˙ O2. Maximal oxygen uptake ( V ˙ O2max), knee extensor maximal isometric voluntary contraction (MVC), peak rate of torque development (RTD), and plantar flexor range-of-motion (PFROM) were also measured. Results: Bivariate correlations showed non-graded (r = 0.403, p = 0.017) and graded (r = 0.413, p = 0.014) net V ˙ O2 were positively related to age. Notably, these relationships strengthened after adjusting for V ˙ O2max. Regression modeling showed age, RTD:MVC ratio (composite of muscle performance), and PFROM together explained 49% and 34% of the variance in non-graded and graded net V ˙ O2, respectively. Further analyses suggested knee extensor MVC moderates the relationship between non-graded net V ˙ O2 and age, accounting for 9% of the variance [ΔR2 = 0.090, F (1,31) = 4.13, p = 0.05]. Conclusion: These data support the premise that, in older women, walking net V ˙ O2 rises with advancing age, and additionally, the RTD:MVC ratio and PFROM are independent correlates of non-graded net V ˙ O2. Exercise interventions with a high degree of training specificity including explosive, velocity-based elements may promote independent mobility in older women. [ABSTRACT FROM AUTHOR]

New findingsWhat is the central question of this study? Does improved metabolic health and insulin sensitivity following a weight-loss and fitness intervention in sedentary, obese women alter exercise-associated fuel metabolism and incomplete mitochondrial fatty acid oxidation (FAO), as tracked by blood acylcarnitine patterns? What is the main finding and its importance? Despite improved fitness and blood sugar control, indices of incomplete mitochondrial FAO increased in a similar manner in response to a fixed load acute exercise bout; this indicates that intramitochondrial muscle FAO is inherently inefficient and is tethered directly to ATP turnover. With insulin resistance or type 2 diabetes mellitus, mismatches between mitochondrial fatty acid fuel delivery and oxidative phosphorylation/tricarboxylic acid cycle activity may contribute to inordinate accumulation of short- or medium-chain acylcarnitine fatty acid derivatives [markers of incomplete long-chain fatty acid oxidation (FAO)]. We reasoned that incomplete FAO in muscle would be ameliorated concurrent with improved insulin sensitivity and fitness following a ∼14 week training and weight-loss intervention in obese, sedentary, insulin-resistant women. Contrary to this hypothesis, overnight-fasted and exercise-induced plasma C4-C14 acylcarnitines did not differ between pre- and postintervention phases. These metabolites all increased robustly with exercise (∼45% of pre-intervention peak oxygen consumption) and decreased during a 20 min cool-down. This supports the idea that, regardless of insulin sensitivity and fitness, intramitochondrial muscle β-oxidation and attendant incomplete FAO are closely tethered to absolute ATP turnover rate. Acute exercise also led to branched-chain amino acid acylcarnitine derivative patterns suggestive of rapid and transient diminution of branched-chain amino acid flux through the mitochondrial branched-chain ketoacid dehydrogenase complex. We confirmed our prior novel observation that a weight-loss/fitness intervention alters plasma xenometabolites [i.e. cis-3,4-methylene-heptanoylcarnitine and γ-butyrobetaine (a co-metabolite possibly derived in part from gut bacteria)], suggesting that host metabolic health regulated gut microbe metabolism. Finally, we considered whether acylcarnitine metabolites signal to muscle-innervating afferents; palmitoylcarnitine at concentrations as low as 1-10 μm activated a subset (∼2.5-5%) of these neurons ex vivo. This supports the hypothesis that in addition to tracking exercise-associated shifts in fuel metabolism, muscle acylcarnitines act as signals of exertion to short-loop somatosensory-motor circuits or to the brain.

Novel plasma metabolite patterns reflective of improved metabolic health (insulin sensitivity, fitness, reduced body weight) were identified before and after a 14-17 wk weight loss and exercise intervention in sedentary, obese insulin-resistant women. To control for potential confounding effects of diet- or microbiome-derived molecules on the systemic metabolome, sampling was during a tightly-controlled feeding test week paradigm. Pairwise and multivariate analysis revealed intervention- and insulin-sensitivity associated: (1) Changes in plasma xeno-metabolites ("non-self" metabolites of dietary or gut microbial origin) following an oral glucose tolerance test (e.g. higher post-OGTT propane-1,2,3-tricarboxylate [tricarballylic acid]) or in the overnight-fasted state (e.g., lower γ-tocopherol); (2) Increased indices of saturated very long chain fatty acid elongation capacity; (3) Increased post-OGTT α-ketoglutaric acid (α-KG), fasting α-KG inversely correlated with Matsuda index, and altered patterns of malate, pyruvate and glutamine hypothesized to stem from improved mitochondrial efficiency and more robust oxidation of glucose. The results support a working model in which improved metabolic health modifies host metabolism in parallel with altering systemic exposure to xeno-metabolites. This highlights that interpretations regarding the origins of peripheral blood or urinary "signatures" of insulin resistance and metabolic health must consider the potentially important contribution of gut-derived metabolites toward the host's metabolome.

Background/Objectives To test the effects of weight loss with and without exercise training (aerobic or resistance) on intra-abdominal adipose tissue (IAAT) and risk factors for cardiovascular disease (CVD). Additionally, CVD risk factors was evaluated before and after weight loss using previously established IAAT cut-points. Subjects/Methods One hundred twenty-two overweight premenopausal women were randomly assigned to one of three groups: (1) diet only (Diet); (2) diet and aerobic training (Diet + AT); or (3) diet and resistance training (Diet + RT); until a BMI of < 25 kg/m.sup.2 was reached. Computerized tomography was used to measure IAAT and blood lipids were measured by assay. Evaluations were made before and after weight loss. Results Though no group-by-time effects were found after weight loss, we observed significant time effects for: IAAT (-38.0%, P < 0.001), total cholesterol (TC) (-2.2%, P = 0.008), low-density lipoprotein cholesterol (LDL-C) (-4.8%, P < 0.001), high-density lipoprotein cholesterol (HDL-C) (+20.2%, P < 0.001), triglycerides (-18.7%, P < 0.001), TC/HDL-C (-16.3%, P < 0.001), and LDL-C/HDL-C (-18.0%, P < 0.001). Following weight loss, 40.2% of all participants reduced IAAT to < 40 cm.sup.2 (IAAT associated with low CVD risk). Furthermore, only 2.5% of participants had an IAAT > 110 cm.sup.2 (IAAT associated with high CVD risk) after weight loss. We also observed that decreases of IAAT were associated with decreased CVD risk factors after weight loss independent of race, changes in %fat mass and changes in maximal oxygen uptake. Conclusions Caloric restriction leading to significant weight loss with or without exercise training appears to be equally effective for reducing IAAT and CVD risk factors., Author(s): Juliano H. Borges [sup.1] [sup.2] , Stephen J. Carter [sup.1] , David R. Bryan [sup.1] , Gary R. Hunter [sup.1] Author Affiliations: (1) Department of Nutrition Sciences, University of [...]

We tested the hypothesis that older men (n = 9, 69 +/- 2 years) would experience greater resistance-training-induced myofiber hypertrophy than older women (n = 5, 66 +/- 1 years) following knee extensor training 3 days per week at 65-80% of one-repetition maximum for 26 weeks. Vastus lateralis biopsies were analyzed for myofiber areas, myosin heavy chain isoform distribution, and levels of mRNA for insulin-like growth factor 1 (IGF-1), IGFR1, and myogenin. Gender x Training interactions (p

Our cross-sectional study aimed to investigate joint specificity of concentric muscle torque enhancement after a maximum eccentric contraction for the knee versus ankle joints across two different movement velocities (120°/s and 180°/s). After a familiarization session, 22 healthy young adults randomly performed concentric (CONC) and maximum eccentric preloaded concentric (EccCONC) muscle strength tests of the knee extensors and ankle plantar flexors of the non-dominant leg on an isokinetic strength testing device. We calculated the ratio between EccCONC and CONC (EccCONC/CONC) for all the conditions as the marker of concentric muscle torque enhancement. Separate two-way (joints x velocity) within repeated measures ANOVAs were used to determine joint-specific torque differences at 120°/s and 180°/s. CONC and EccCONC were greater for the knee extensors versus ankle plantar flexors at 120°/s and 180°/s (32.86%--102%; p < 0.001 for both); however, EccCONC/CONC was greater for the ankle plantar flexors than knee extensors at 120°/s (52.4%; p < 0.001) and 180°/s (41.9%; p < 0.001). There was a trend of greater EccCONC/CONC for the knee extensors at 180°/s than 120°/s (6.6%; p = 0.07). Our results show that greater concentric muscle torque enhancement after a maximal eccentric contraction occurs for the ankle plantar flexors versus knee extensors. Whether the joint- specificity of concentric muscle torque enhancement after a maximal eccentric contraction differentially affects sports performance is unknown. Our data provide a reference framework to investigate joint-specific concentric muscle torque enhancement for general and clinical athletic populations. [ABSTRACT FROM AUTHOR]