Re-evaluating lipotoxic triggers in skeletal muscle: relating intramyocellular lipid metabolism to insulin sensitivity

Ectopic fat accumulation has been linked to lipotoxic events, including the development of insulin resistance in skeletal muscle. Indeed, intramyocellular lipid storage is strongly associated with the development of type 2 diabetes. Research during the last two decades has provided evidence for a role of lipid intermediates like diacylglycerol and ceramide in the induction of lipid-induced insulin resistance. However, recently novel data has been gathered that suggest that the relation between lipid intermediates and insulin resistance is less straightforward than has been previously suggested, and that there are several routes towards lipid-induced insulin resistance. For example, research in this field has shifted towards imbalances in lipid metabolism and lipid droplet dynamics. Next to imbalances in key lipogenic and lipolytic proteins, lipid droplet coat proteins appear to be essential for proper intramyocellular lipid storage, turnover and protection against lipid-induced insulin resistance.Here, we discuss the current knowledge on lipid-induced insulin resistance in skeletal muscle with a focus on the evidence from human studies. Furthermore, we discuss the available data that provides supporting mechanistic information.     

The lipid droplet coat protein perilipin 5 also localizes to muscle mitochondria

Perilipin 5 (PLIN5/OXPAT) is a lipid droplet (LD) coat protein mainly present in tissues with a high fat-oxidative capacity, suggesting a role for PLIN5 in facilitating fatty acid oxidation. Here, we investigated the role of PLIN5 in fat oxidation in skeletal muscle. In human skeletal muscle, we observed that PLIN5 (but not PLIN2) protein content correlated tightly with OXPHOS content and in rat muscle PLIN5 content correlated with mitochondrial respiration rates on a lipid-derived substrate. This prompted us to examine PLIN5 protein expression in skeletal muscle mitochondria by means of immunogold electron microscopy and Western blots in isolated mitochondria. These data show that PLIN5, in contrast to PLIN2, not only localizes to LD but also to mitochondria, possibly facilitating fatty acid oxidation. Unilateral overexpression of PLIN5 in rat anterior tibialis muscle augmented myocellular fat storage without increasing mitochondrial density as indicated by the lack of change in protein content of five components of the OXPHOS system. Mitochondria isolated from PLIN5 overexpressing muscles did not possess increased fatty acid respiration. Interestingly though, (14)C-palmitate oxidation assays in muscle homogenates from PLIN5 overexpressing muscles revealed a 44.8% (P?=?0.05) increase in complete fatty acid oxidation. Thus, in mitochondrial isolations devoid of LD, PLIN5 does not augment fat oxidation, while in homogenates containing PLIN5-coated LD, fat oxidation is higher upon PLIN5 overexpression. The presence of PLIN5 in mitochondria helps to understand why PLIN5, in contrast to PLIN2, is of specific importance in fat oxidative tissues. Our data suggests involvement of PLIN5 in directing fatty acids from the LD to mitochondrial fatty acid oxidation.     

A new species of Polygala (Polygalaceae) from ultramafic soils in Sekhukhuneland,South Africa,with notes on its ecology

Polygala sekhukhuniensis Retief, Siebert & A.E.Van Wyk (Polygala; section Polygala; subsection Heterolophus), a new species with a restricted range in Sekhukhuneland, South Africa, is described, illustrated and compared with other members of the genus. It is a dwarf shrub that can be distinguished by its much-branched habit, sparsely flowered inflorescences, pink alae with darker pink veins, brown to black seed testa, and oblate pollen grains with pronounced opercula. Geographically, P. sekhukhuniensis is confined to heavily eroded localized sites, a natural geomorphological feature of some of the highly water-dispersible soils derived from ultramafic rocks in the valleys of the Steelpoort River and its tributaries in the Sekhukhuneland Centre of Plant Endemism. P. sekhukhuniensis is a calciotrophic excluder of heavy metals that accumulates Ca in its leaves. It is ecologically compared with co-occurring species of Polygala on ultramafic-derived soil.     

Chemical imaging of lipid droplets in muscle tissues using hyperspectral coherent Raman microscopy

The accumulation of lipids in non-adipose tissues is attracting increasing attention due to its correlation with obesity. In muscle tissue, ectopic deposition of specific lipids is further correlated with pathogenic development of insulin resistance and type 2 diabetes. Most intramyocellular lipids are organized into lipid droplets (LDs), which are metabolically active organelles. In order to better understand the putative role of LDs in pathogenesis, insight into both the location of LDs and nearby chemistry of muscle tissue is very useful. Here, we demonstrate the use of label-free coherent anti-Stokes Raman scattering (CARS) microscopy in combination with multivariate, chemometric analysis to visualize intracellular lipid accumulations in ex vivo muscle tissue. Consistent with our previous results, hyperspectral CARS microscopy showed an increase in LDs in tissues where LD proteins were overexpressed, and further chemometric analysis showed additional features morphologically (and chemically) similar to mitochondria that colocalized with LDs. CARS imaging is shown to be a very useful method for label-free stratification of ectopic fat deposition and cellular organelles in fresh tissue sections with virtually no sample preparation.     

AFLPs are incompatible with RAPD and morphological data in Pennisetum purpureum (Napier grass)

Accessions of Pennisetum purpureum in agricultural research centres in sub-Saharan Africa were genotyped using Amplified Fragment Length Polymorphisms (AFLPs) using primer combinations MluI/MseI. Cluster analyses of resulting bands suggested that the samples could be grouped into five large and five small-sized clusters. Principal coordinate analysis revealed two major clusters being well separated, with bulk of the samples forming one, poorly structured cluster. Our analyses failed to reveal the regional groupings found in previous studies using a subset of our sample universe and based on RAPDs as well as morphological and agronomical data. The inability of the AFLP data to clearly demarcate accessions is ascribed to either the presence of high levels of genetic uniformity, or non-optimal primers and/or bad germplasm management practices. The re-registration of all accessions, based on DNA barcoding, is suggested as a means to resolve the lingering problems regarding the identity of accessions.     

One-Seeded Fruits in the Core Caryophyllales: Their Origin and Structural Diversity

The core Caryophyllales consist of approximately 30 families (12 000 species) distributed worldwide. Many members evolved one-seeded or conjoined fruits, but their origin and structural diversity have not been investigated. A comparative anatomical investigation of the one-seeded fruits within the core Caryophyllales was conducted. The origin of the one-seeded fruits and the evolutionary reconstructions of some carpological characters were traced using a tree based on rbcl and matK data in order to understand the ancestral characters and their changes. The one-seeded fruit type is inferred to be an ancestral character state in core Caryophyllales, with a subsequent increase in the seed number seen in all major clades. Most representatives of the ‘Earlier Diverging’ clade are distinguished in various carpological traits. The organization of the pericarp is diverse in many groups, although fruits with a dry, many-layered pericarp, consisting of sclerenchyma as outer layers and a thin-walled parenchyma below, with seeds occupying a vertical embryo position, are likely ancestral character states in the core Caryophyllales clade. Several carpological peculiarities in fruit and seed structure were discovered in obligate one-seeded Achatocarpaceae, Chenopodiaceae, Nyctaginaceae, Seguieriaceae and Sarcobataceae. The horizontal embryo evolved in only certain groups of Chenopodiaceae. The bar-thickening of endotegmen cells appears to be an additional character typical of core Caryophyllales. The syncarpy-to-lysicarpy paradigm in Caryophyllaceae needs to be reinterpreted.