685 research outputs found
Muscle-specific Perilipin2 down-regulation affects lipid metabolism and induces myofiber hypertrophy.
BACKGROUND: Perilipin2 (Plin2) belongs to a family of five highly conserved
proteins, known for their role in lipid storage. Recent data indicate that Plin2
has an important function in cell metabolism and is involved in several human
pathologies, including liver steatosis and Type II diabetes. An association
between Plin2 and lower muscle mass and strength has been found in elderly and
inactive people, but its function in skeletal muscle is still unclear. Here, we
addressed the role of Plin2 in adult muscle by gain and loss of function
experiments.
METHODS: By mean of in vivo Plin2 down-regulation (shPlin2) and overexpression
(overPlin2) in murine tibialis anterior muscle, we analysed the effects of Plin2
genetic manipulations on myofiber size and lipid composition. An analysis of
skeletal muscle lipid composition was also performed in vastus lateralis samples
from young and old patients undergoing hip surgery.
RESULTS: We found that Plin2 down-regulation was sufficient to induce a 30%
increase of myofiber cross-sectional area, independently of mTOR pathway.
Alterations of lipid content and modulation of genes involved in lipid synthesis
occurred in hypertrophic muscles. In particular, we showed a decrease of
triglycerides, ceramides, and phosphatidylcoline:phosphatidylethanolamine ratio,
a condition known to impact negatively on muscle function. Plin2 overexpression
did not change fibre size; however, lipid composition was strongly affected in a
way that is similar to that observed in human samples from old patients.
CONCLUSIONS: Altogether these data indicate that Plin2 is a critical mediator for
the control of muscle mass, likely, but maybe not exclusively, through its
critical role in the regulation of intracellular lipid content and composition
The mitochondrial genome of the arbuscular mycorrhizal fungus Gigaspora margarita reveals two unsuspected trans-splicing events of group I introns
Demography of the bottlenose dolphin Tursiops truncatus (Mammalia: Delphinidae) in the Eastern Ligurian Sea (NW Mediterranean): quantification of female reproductive parameters
AbstractThe reproductive histories of 41 adult bottlenose dolphin females were analysed using photo-identification data collected between 2006 and 2014 in four sub-areas of the eastern Ligurian Sea (northwest Mediterranean). The Rapallo sub-area revealed the highest (highly significant) frequency of encounters (per unit effort) of reproductive females in association with young individuals, therefore emerging as a candidate nursery area in the region. The estimated fertility rate of adult females ranged between 290 and 407 births per 1000 individuals per year, higher than that of other known bottlenose dolphin populations, with a calving interval between 2.45 and 3.5 years. These results will be useful for projecting future trends of this (sub)population
X-chromosome-linked miR548am-5p is a key regulator of sex disparity in the susceptibility to mitochondria-mediated apoptosis.
Sex dimorphism in cell response to stress has previously been investigated by different research groups. This dimorphism could be at least in part accounted for by sex-biased expression of regulatory elements such as microRNAs (miRs). In order to spot previously unknown miR expression differences we took advantage of prior knowledge on specialized databases to identify X chromosome-encoded miRs potentially escaping X chromosome inactivation (XCI). MiR-548am-5p emerged as potentially XCI escaper and was experimentally verified to be significantly up-regulated in human XX primary dermal fibroblasts (DFs) compared to XY ones. Accordingly, miR-548am-5p target mRNAs, e.g. the transcript for Bax, was differently modulated in XX and XY DFs. Functional analyses indicated that XY DFs were more prone to mitochondria-mediated apoptosis than XX ones. Experimentally induced overexpression of miR548am-5p in XY cells by lentivirus vector transduction decreased apoptosis susceptibility, whereas its down-regulation in XX cells enhanced apoptosis susceptibility. These data indicate that this approach could be used to identify previously unreported sex-biased differences in miR expression and that a miR identified with this approach, miR548am-5p, can account for sex-dependent differences observed in the susceptibility to mitochondrial apoptosis of human DFs
Clinical, biochemical and molecular characterization of prosaposin deficiency
Prosaposin (PSAP) deficiency is an ultra-rare, fatal infantile lysosomal storage disorder (LSD) caused by variants in the PSAP gene, with 7 subjects reported so far. Here, we provide the clinical, biochemical and molecular characterization of two additional PSAP deficiency cases. Lysoplex, a targeted resequencing approach was utilized to identify the variant in the first patient, while quantification of plasma lysosphingolipids (lysoSLs), assessed by liquid chromatography mass spectrometry (LC-MS/MS) and brain magnetic resonance imaging (MRI), followed by Sanger sequencing allowed to attain diagnosis in the second case. Functional studies were carried out on patients' fibroblast lines to explore the functional impact of variants. The two patients were homozygous for two different truncating PSAP mutations (c.895G>T, p.Glu299*; c.834_835delGA, p.Glu278Aspfs*27). Both variants led to a complete lack of processed transcript. LC-MS/MS and brain MRI analyses consistently provided a distinctive profile in the two children. Quantification of specific plasma lysoSLs revealed elevated levels of globotriaosylsphingosine (lysoGb3) and glucosylsphingosine (GlSph), and accumulation of autophagosomes, due to a decreased autophagic flux, was observed. This report documents the successfully use of plasma lysoSLs profiling in the PSAP deficiency diagnosis, as a reliable and informative tool to obtain a preliminary information in infantile cases with complex traits displaying severe neurological signs and visceral involvement.Prosaposin (PSAP) deficiency is an ultra-rare, fatal infantile lysosomal storage disorder (LSD) caused by variants in the PSAP gene, with seven subjects reported so far. Here, we provide the clinical, biochemical and molecular characterization of two additional PSAP deficiency cases. Lysoplex, a targeted resequencing approach was utilized to identify the variant in the first patient, while quantification of plasma lysosphingolipids (lysoSLs), assessed by liquid chromatography mass spectrometry (LC-MS/MS) and brain magnetic resonance imaging (MRI), followed by Sanger sequencing allowed to attain diagnosis in the second case. Functional studies were carried out on patients' fibroblast lines to explore the functional impact of variants. The two patients were homozygous for two different truncating PSAP mutations (c.895G>T, p.Glu299*; c.834_835delGA, p.Glu278Aspfs*27). Both variants led to a complete lack of processed transcript. LC-MS/MS and brain MRI analyses consistently provided a distinctive profile in the two children. Quantification of specific plasma lysoSLs revealed elevated levels of globotriaosylsphingosine (LysoGb3) and glucosylsphingosine (GlSph), and accumulation of autophagosomes, due to a decreased autophagic flux, was observed. This report documents the successful use of plasma lysoSLs profiling in the PSAP deficiency diagnosis, as a reliable and informative tool to obtain a preliminary information in infantile cases with complex traits displaying severe neurological signs and visceral involvement
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