Featured Articles

Volume 5 | No. 3 | March 2016

Altered DNA methylation of glycolytic and lipogenic genes in liverKirchner and colleagues show that mRNA expression of targets along the glycolytic pathway are increased in the liver of obese people, concomitant with DNA hypomethylation of the respective genes at an important ATF-motif regulatory site. Constitutive activation of these pathways is associated with protein kinase C epsilon activation and hypomethylation, which may lead to the development of hepatic insulin resistance and hepatic steatosis.

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High-fat diet reprograms the epigenome of rat spermatozoaThe results of Barbosa et al. provide insight into mechanisms by which high-fat diet reprograms the epigenome of sperm cells and affects the metabolic phenotype of the offspring throughout several generations. The authors also provide evidence that altered miRNA let-7c expression in sperm is passed down to the adipose tissue of the offspring, leading to a transcriptomic shift in let-7c predicted targets. In conclusion, reprogramming of sperm let-7c expression may constitute a mechanism by which high-fat diet can alter the metabolism of the offspring.

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Undernutrition delays a key step in the maturation of hypothalamic feeding circuitsDe Solis and colleagues explore whether effects of moderate postnatal undernutrition (UN) to increase post-weaning growth rates are associated with impairments in the maturation of systems that provide negative feedback to the orexigenic actions of NPY/AgRP/GABA (NAG) neurons. They find that UN delays the development of the homeostatic regulation of feeding, which is tightly correlated with the onset of potassium (KATP) channel expression and the maturation of electrophysiological properties of NAG neurons.

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Acyl CoA synthetase 5 (ACSL5) ablation in mice increases energy expenditure and insulin sensitivityBowman et al. demonstrate in a newly generated line of acyl-CoA synthetase 5 (ACSL5) deficient mice that the in vivo consequences of ACSL ablation are reduced adiposity, circulating triglyceride and glucose levels, increased insulin sensitivity and energy expenditure, and reduced rate of intestinal triglyceride absorption. They find potent increases in hepatic mRNA expression and circulating serum levels of fibroblast growth factor 21 (FGF21), The increased circulating level of FGF21 is associated with the increased mRNA levels of Ucp1, consistent with effects of FGF21 to promote conversion of white to beige adipocytes, leading to increased rates of energy expenditure.

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Impaired glucose metabolism with muscle-specific glycogen synthase 1 deletionXirouchaki, Mangiafico and colleagues suggest that muscle glycogen synthase 1 (gys1) plays a major role in muscle glycogen synthesis and non-oxidative glucose metabolism as a muscle-specific gys1 deletion in the adult mouse can contribute to peripheral insulin resistance and glucose intolerance. In addition, gys1 is crucial for muscle function during contraction, exercise and endurance capacity as muscle glycogen depletion is a leading factor in impaired muscle performance and fatigue development during exercise.

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Integration of ATAC-seq and RNA-seq identifies human alpha cell and beta cell signature genesAckermann and colleagues provide a novel resource for identifying open chromatin regions in human α-, β-, and acinar cells. This dataset builds upon the growing body of genome-wide epigenetic studies performed in purified human α- and β-cells. They show that integrating ATAC-seq (Assay for Transposase-Accessible Chromatin with high throughput sequencing) data with other epigenetic information enhances interpretation of computational results, and they anticipate that this ATAC-seq dataset will be useful for integration with future genomic analyses of human islets.

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Sex difference in physical activity driven by hypothalamic POMC neuronsMelanocortin peptides encoded by the pro-opiomelanocortin gene (Pomc) are key regulators of energy balance. The findings of Burke and Doslikova et al. support the functional heterogeneity of hypothalamic POMC neurons, revealing that the source synthesized within 5-hydroxytryptamine 2c receptor expressing neurons is sufficient to regulate energy intake and insulin sensitivity in male and female mice. Moreover, these data provide evidence for a specific neurochemical basis for levels of reduced physical activity and reveal that the molecular underpinnings of the impetus to engage in physical activity are differentially modulated in males and females.

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The 60 Second Metabolist
In this section authors briefly report on their work recently published in Molecular Metabolism.

Watch the most recent interview by clicking the video still. The link "referring article" directs you to this author's publication.



Giles Yeo
University of Cambridge, UK
Referring article

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