The effects of omega-3 polyunsaturated fatty acids on AMPK activation and lipid metabolism in skeletal muscle

Intramyocellular lipid accumulation and low lipid oxidative capacity contribute to the formation of insulin resistance, but omega-3 polyunsaturated fatty acids (n-3 PUFA) are shown to attenuate insulin resistance caused by high levels of saturated fats. The AMP-activated protein kinase (AMPK) promotes lipid oxidation and oxidative gene expression, highlighting its possible role in promoting insulin sensitivity by reducing lipid content and improving oxidative capacity. This study evaluated the effects of n-3 PUFA on the AMPK pathway and alterations to lipid content, oxidative markers, and insulin signaling proteins in a muscle cell culture model, with the hypothesis that n-3 PUFA would attenuate the saturated fatty acid-induced increase in intramyocellular lipids and detriments to the AMPK pathway, oxidative markers, and insulin signaling. The findings confirm that n-3 PUFA both attenuate saturated fatty acid-induced increases in intramyocellular lipid content and normalize insulin signaling and oxidative metabolic markers, though independently of the AMPK signaling pathway

Docosahexaenoic acid counteracts palmitate-induced endoplasmic reticulum stress in C2C12 myotubes: Impact on muscle atrophy

Lipid accumulation in skeletal muscle results in dysregulation of protein meta- bolism and muscle atrophy. We previously reported that treating C2C12 myo- tubes with palmitate (PA), a saturated fatty acid, increases the overall rate of proteolysis via activation of the ubiquitin-proteasome and autophagy systems; co-treatment with the omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) prevents the PA-induced responses. Others have reported that PA induces endoplasmic reticulum (ER) stress which initiates the unfolded pro- tein response (UPR), a collective group of responses that can lead to activa- tion of caspase-mediated proteolysis and autophagy. Presently, we tested the hypothesis that DHA protects against PA-induced ER stress/UPR and its atro- phy-related responses in muscle cells. C2C12 myotubes were treated with 500 lmol/L PA and/or 100 lmol/L DHA for 24 h. Proteins and mRNA asso- ciated with ER stress/UPR, autophagy, and caspase-3 activation were evalu- ated. PA robustly increased the phosphorylation of protein kinase R (PKR)- like ER kinase (PERK) and eukaryotic initiation factor 2a (eIF2a). It also increased the mRNAs encoding activating transcription factor 4 (ATF4), spliced X-box binding protein 1 (XBP1s), C/EBP homologous protein (CHOP), and autophagy-related 5 (Atg5) as well as the protein levels of the PERK target nuclear factor erythroid 2-related factor (Nrf2), CHOP, and cleaved (i.e., activated) caspase-3. Co-treatment with DHA prevented all of the PA-induced responses. Our results indicate that DHA prevents PA- induced muscle cell atrophy, in part, by preventing ER stress/UPR, a process that leads to activation of caspase-mediated proteolysis and an increase in expression of autophagy-related genes

Palmitate-induced ER stress and inhibition of protein synthesis in cultured myotubes does not require Toll-like receptor 4

Saturated fatty acids, such as palmitate, are elevated in metabolically dysfunctional condi- tions like type 2 diabetes mellitus. Palmitate has been shown to impair insulin sensitivity and suppress protein synthesis while upregulating proteolytic systems in skeletal muscle. Increased sarco/endoplasmic reticulum (ER) stress and subsequent activation of the unfolded protein response may contribute to the palmitate-induced impairment of muscle protein synthesis. In some cell types, ER stress occurs through activation of the Toll-like receptor 4 (TLR4). Given the link between ER stress and suppression of protein synthesis, we investigated whether palmitate induces markers of ER stress and protein synthesis by activating TLR4 in cultured mouse C2C12 myotubes. Myotubes were treated with vehicle, a TLR4-specific ligand (lipopolysaccharides), palmitate, or a combination of palmitate plus a TLR4-specific inhibitor (TAK-242). Inflammatory indicators of TLR4 activation (IL-6 and TNFα) and markers of ER stress were measured, and protein synthesis was assessed using puromycin incorporation. Palmitate substantially increased the levels of IL-6, TNF-α, CHOP, XBP1s, and ATF 4 mRNAs and augmented the levels of CHOP, XBP1s, phospho- PERK and phospho-eIF2α proteins. The TLR4 antagonist attenuated both acute palmitate and LPS-induced increases in IL-6 and TNFα, but did not reduce ER stress signaling with either 6 h or 24 h palmitate treatment. Similarly, treating myotubes with palmitate for 6 h caused a 43% decline in protein synthesis consistent with an increase in phospho-eIF2α, and the TLR4 antagonist did not alter these responses. These results suggest that palmitate does not induce ER stress through TLR4 in muscle, and that palmitate impairs protein syn- thesis in skeletal muscle in part by induction of ER stress

Examining gradients in ecosystem novelty: fish assemblage structure in an invaded Everglades canal system

Novel ecosystems result from a combination of altered historical abiotic regimes and new species assemblages. In freshwater systems, novel environmental conditions often result from large-scale changes to hydrological connectivity as well as species invasions. Novel environmental conditions may affect the survival of aquatic fauna by altering dispersal patterns and resource fluctuations, and/or may impose physiological constraints on native species evolutionarily adapted to particular environments. Further, novel systems can provide insight into processes driving community structure because re-sorting or filtering of regional biota is a likely consequence of decoupling from historical conditions. Although several studies document the presence of novel conditions, few examine variation or gradients in novelty. The Florida Everglades is a highly invaded and hydrologically altered system characterized by a large network of canals that compartmentalize the ecosystem and act to both increase and decrease connectivity. Little is known about how canals in this region function as habitat for native and nonnative fishes, the extent to which these canals may function as novel habitats, and how these habitat characteristics may influence distribution, abundance, and assembly patterns. In this study, we examined native and nonnative fish assemblages along a gradient of novelty, defined as the loss of wetland connectivity, influence of the natural hydrological regime, and habitat complexity (well connected to leveed canals). As novelty increased, native species richness and abundance strongly declined and the contribution of nonnatives increased to nearly 50%. Vast differences in community structure across the novelty gradient were strongly influenced by spatial factors and secondarily by hydrological factors, while habitat and abiotic factors were of very low relevance. Natives and nonnatives had opposing responses to key hydrological and habitat characteristics. Abundance of native fishes declined with decreased connectivity to adjacent marshes and canal littoral zone width, while nonnative fishes increased significantly in the most novel canals. Our results suggest that the inherent loss of natural environmental conditions and subsequent replacement by novel ones can lead to extensive changes in fish community structure. Success or failure at maintaining native assemblages will rely heavily on natural resource manager\u27s ability to incorporate natural environmental characteristics with ecosystem restoration

Lipid modulation of skeletal muscle mass and function

Loss of skeletal muscle mass is a characteristic feature of various pathologies including cancer, diabetes, and obesity, as well as being a general feature of ageing. However, the processes underlying its pathogenesis are not fully understood and may involve multiple factors. Importantly, there is growing evidence which supports a role for fatty acids and their derived lipid intermediates in the regulation of skeletal muscle mass and function. In this review, we discuss evidence pertaining to those pathways which are involved in the reduction, increase and/or preservation of skeletal muscle mass by such lipids under various pathological conditions, and highlight studies investigating how these processes may be influenced by dietary supplementation as well as genetic and/or pharmacological intervention

Cost-effective ecological restoration

© 2015 Society for Ecological Restoration Ecological restoration is a multibillion dollar industry critical for improving degraded habitat. However, most restoration is conducted without clearly defined success measures or analysis of costs. Outcomes are influenced by environmental conditions that vary across space and time, yet such variation is rarely considered in restoration planning. Here, we present a cost-effectiveness analysis of terrestrial restoration methods to determine how practitioners may restore the highest native plant cover per dollar spent. We recorded costs of 120 distinct methods and described success in terms of native versus non-native plant germination, growth, cover, and density. We assessed effectiveness using a basic, commonly used metric (% native plant cover) and developed an index of cost-effectiveness (% native cover per dollar spent on restoration). We then evaluated success of multiple methods, given environmental variation across topography and multiple years, and found that the most successful method for restoring high native plant cover is often different from the method that results in the largest area restored per dollar expended, given fixed mitigation budgets. Based on our results, we developed decision-making trees to guide practitioners through established phases of restoration-site preparation, seeding and planting, and maintenance. We also highlight where additional research could inform restoration practice, such as improved seasonal weather forecasts optimizing allocation of funds in time or valuation practices that include costs of specific outcomes in the collection of in lieu fees