Bananas and pears vary in sugar and phenolic profiles, and metabolomics was utilized to measure their influence on exercise performance and recovery. Male athletes (N = 20) cycled for 75 km while consuming water (WATER), bananas (BAN), or pears (PEAR) (0.6 g carbohydrate/kg each hour) in randomized order. UPLC-MS/MS and the library of purified standards maintained by Metabolon (Durham, NC) were used to analyze metabolite shifts in pre- and postexercise (0-h, 1.5-h, 21-h) blood samples. Performance times were 5.0% and 3.3% faster during BAN and PEAR versus WATER (P = 0.018 and P = 0.091, respectively), with reductions in cortisol, IL-10, and total leukocytes, and increases in blood glucose, insulin, and FRAP. Partial Least Square Discriminant Analysis (PLS-DA) showed a distinct separation between trials immediately (R(2)Y = 0.877, Q(2)Y = 0.457) and 1.5-h postexercise (R(2)Y = 0.773, Q(2)Y = 0.441). A total of 107 metabolites (primarily lipid-related) increased more than 2-fold during WATER, with a 48% and 52% reduction in magnitude during BAN and PEAR recovery (P < 0.001). Increases in metabolites unique to BAN and PEAR included fructose and fruit constituents, and sulfated phenolics that were related to elevated FRAP. These data indicate that BAN and PEAR ingestion improves 75-km cycling performance, attenuates fatty acid utilization and oxidation, and contributes unique phenolics that augment antioxidant capacity.
Alzheimer's Disease (ad) associates with insulin resistance and low aerobic capacity suggestive of impaired skeletal muscle mitochondrial function. However, direct measures of muscle mitochondrial function have not been performed in ad. This study (n = 50) compared skeletal muscle mitochondrial respiratory function and gene expression profiling in cognitively healthy older adults (CH; n = 24) to 26 individuals in the earliest phase of ad-related cognitive decline, mild cognitive impairment (MCI; n = 11) or MCI taking an ad medication, donepezil (MCI + med; n = 15). Mitochondrial respiratory kinetics were measured in permeabilized muscle fibers from skeletal muscle biopsies of the vastus lateralis. Untreated MCI subjects exhibited lower lipid-stimulated skeletal muscle mitochondrial respiration (State 3, ADP-stimulated) than both CH (P = 0.043) and MCI + med (P = 0.007) groups. MCI also exhibited poorer mitochondrial coupling control compared to CH (P = 0.014). RNA sequencing of skeletal muscle revealed unique differences in mitochondrial function and metabolism genes based on both MCI status (CH vs. MCI) and medication treatment (MCI vs. MCI + med). MCI + med modified over 600 skeletal muscle genes compared to MCI suggesting donepezeil powerfully impacts the transcriptional profile of skeletal muscle. Overall, skeletal muscle mitochondrial respiration is altered in untreated MCI but normalized in donepezil-treated MCI participants while mitochondrial leak control is impaired regardless of medication status. These results provide further evidence that skeletal muscle mitochondrial changes occur in the very early stages of ad, but is likely influenced by a common ad medicine. Further study of mitochondrial bioenergetics and the influence of transcriptional regulation in early ad is warranted.
Oxygenated lipids, called “oxylipins,” serve a variety of important signaling roles within the cell. Oxylipins have been linked to inflammation and vascular function, and blood patterns have been shown to differ in type 2 diabetes (T2D). Because these factors (inflammation, vascular function, diabetes) are also associated with Alzheimer’s disease (AD) risk, we set out to characterize the serum oxylipin profile in elderly and AD subjects to understand if there are shared patterns between AD and T2D. We obtained serum from 126 well-characterized, overnight-fasted elderly individuals who underwent a stringent cognitive evaluation and were determined to be cognitively healthy or AD. Because the oxylipin profile may also be influenced by T2D, we assessed nondiabetic and T2D subjects separately. Within nondiabetic individuals, cognitively healthy subjects had higher levels of the nitrolipid 10-nitrooleate (16.8% higher) compared to AD subjects. AD subjects had higher levels of all four dihydroxyeicosatrienoic acid (DiHETrE) species: 14,15-DiHETrE (18% higher), 11,12 DiHETrE (18% higher), 8,9-DiHETrE (23% higher), and 5,6-DiHETrE (15% higher). Within T2D participants, we observed elevations in 14,15-dihydroxyeicosa-5,8,11-trienoic acid (14,15-DiHETE; 66% higher), 17,18-dihydroxyeicosa-5,8,11,14-tetraenoic acid (17,18-DiHETE; 29% higher) and 17-hydroxy-4,7,10,13,15,19-docosahexaenoic acid (17-HDoHE; 105% higher) and summed fatty acid diols (85% higher) in subjects with AD compared to cognitively healthy elderly, with no differences in the DiHETrE species between groups. Although these effects were no longer significant following stringent adjustment for multiple comparisons, the consistent effects on groups of molecules with similar physiological roles, as well as clear differences in the AD-related profiles within nondiabetic and T2D individuals, warrant further research into these molecules in the context of AD.
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